title: HIV

text: HIV is similar in structure to other retroviruses. It is roughly spherical with a diameter of about 120 nm, around 100,000 times smaller in volume than a red blood cell. It is composed of two copies of positive-sense single-stranded RNA that codes for the virus's nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24. The single-stranded RNA is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as reverse transcriptase, proteases, ribonuclease and integrase. A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle.


title: HIV

text: This is, in turn, surrounded by the viral envelope, that is composed of the lipid bilayer taken from the membrane of a human host cell when the newly formed virus particle buds from the cell. The viral envelope contains proteins from the host cell and relatively few copies of the HIV envelope protein, which consists of a cap made of three molecules known as glycoprotein (gp) 120, and a stem consisting of three gp41 molecules that anchor the structure into the viral envelope. The envelope protein, encoded by the HIV "env" gene, allows the virus to attach to target cells and fuse the viral envelope with the target cell's membrane releasing the viral contents into the cell and initiating the infectious cycle.


title: HIV

text: As the sole viral protein on the surface of the virus, the envelope protein is a major target for HIV vaccine efforts. Over half of the mass of the trimeric envelope spike is N-linked glycans. The density is high as the glycans shield the underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic and Golgi apparatus. The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on human glycoproteins that are secreted or present on a cell surface. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to, or are adapted to cope with, these envelope glycans.


title: HIV

text: The molecular structure of the viral spike has now been determined by X-ray crystallography and cryogenic electron microscopy. These advances in structural biology were made possible due to the development of stable recombinant forms of the viral spike by the introduction of an intersubunit disulphide bond and an isoleucine to proline mutation (radical replacement of an amino acid) in gp41. The so-called SOSIP trimers not only reproduce the antigenic properties of the native viral spike, but also display the same degree of immature glycans as presented on the native virus. Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising epitopes than recombinant monomeric gp120, which act to suppress the immune response to target epitopes.


title: HIV

text: The RNA genome consists of at least seven structural landmarks (LTR, TAR, RRE, PE, SLIP, CRS, and INS), and nine genes ("gag", "pol", and "env", "tat", "rev", "nef", "vif", "vpr", "vpu", and sometimes a tenth "tev", which is a fusion of "tat", "env" and "rev"), encoding 19 proteins. Three of these genes, "gag", "pol", and "env", contain information needed to make the structural proteins for new virus particles. For example, "env" codes for a protein called gp160 that is cut in two by a cellular protease to form gp120 and gp41. The six remaining genes, "tat", "rev", "nef", "vif", "vpr", and "vpu" (or "vpx" in the case of HIV-2), are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus (replicate), or cause disease.


title: HIV

text: The two "tat" proteins (p16 and p14) are transcriptional transactivators for the LTR promoter acting by binding the TAR RNA element. The TAR may also be processed into microRNAs that regulate the apoptosis genes "ERCC1" and "IER3". The "rev" protein (p19) is involved in shuttling RNAs from the nucleus and the cytoplasm by binding to the RRE RNA element. The "vif" protein (p23) prevents the action of APOBEC3G (a cellular protein that deaminates cytidine to uridine in the single-stranded viral DNA and/or interferes with reverse transcription). The "vpr" protein (p14) arrests cell division at G2/M. The "nef" protein (p27) down-regulates CD4 (the major viral receptor), as well as the MHC class I and class II molecules.


title: HIV

text: "Nef" also interacts with SH3 domains. The "vpu" protein (p16) influences the release of new virus particles from infected cells. The ends of each strand of HIV RNA contain an RNA sequence called a long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell. The Psi element is involved in viral genome packaging and recognized by "gag" and "rev" proteins. The SLIP element () is involved in the frameshift in the "gag"-"pol" reading frame required to make functional "pol".


title: HIV

text: The term viral tropism refers to the cell types a virus infects. HIV can infect a variety of immune cells such as CD4 T cells, macrophages, and microglial cells. HIV-1 entry to macrophages and CD4 T cells is mediated through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells' membrane and also with chemokine co-receptors.


title: HIV

text: Macrophage-tropic (M-tropic) strains of HIV-1, or non-syncytia-inducing strains (NSI; now called R5 viruses) use the "β"-chemokine receptor, CCR5, for entry and are thus able to replicate in both macrophages and CD4 T cells. This CCR5 co-receptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV infection. They appear to be the first cells infected by HIV and perhaps the source of HIV production when CD4 cells become depleted in the patient. Macrophages and microglial cells are the cells infected by HIV in the central nervous system. In the tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce huge amounts of virus.


title: HIV

text: T-tropic strains of HIV-1, or syncytia-inducing strains (SI; now called X4 viruses) replicate in primary CD4 T cells as well as in macrophages and use the "α"-chemokine receptor, CXCR4, for entry.


title: HIV

text: Dual-tropic HIV-1 strains are thought to be transitional strains of HIV-1 and thus are able to use both CCR5 and CXCR4 as co-receptors for viral entry.


title: HIV

text: The "α"-chemokine SDF-1, a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates. It does this by down-regulating the expression of CXCR4 on the surface of HIV target cells. M-tropic HIV-1 isolates that use only the CCR5 receptor are termed R5; those that use only CXCR4 are termed X4, and those that use both, X4R5. However, the use of co-receptors alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection and HIV can also infect a subtype of myeloid dendritic cells, which probably constitute a reservoir that maintains infection when CD4 T cell numbers have declined to extremely low levels.


title: HIV

text: Some people are resistant to certain strains of HIV. For example, people with the CCR5-Δ32 mutation are resistant to infection by the R5 virus, as the mutation leaves HIV unable to bind to this co-receptor, reducing its ability to infect target cells.


title: HIV

text: Sexual intercourse is the major mode of HIV transmission. Both X4 and R5 HIV are present in the seminal fluid, which enables the virus to be transmitted from a male to his sexual partner. The virions can then infect numerous cellular targets and disseminate into the whole organism. However, a selection process leads to a predominant transmission of the R5 virus through this pathway. In patients infected with subtype B HIV-1, there is often a co-receptor switch in late-stage disease and T-tropic variants that can infect a variety of T cells through CXCR4. These variants then replicate more aggressively with heightened virulence that causes rapid T cell depletion, immune system collapse, and opportunistic infections that mark the advent of AIDS. HIV-positive patients acquire an enormously broad spectrum of opportunistic infections, which was particularly problematic prior to the onset of HAART therapies; however, the same infections are reported among HIV-infected patients examined post-mortem following the onset of antiretroviral therapies. Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of CCR5 may be a key step in the progression to AIDS. A number of studies with subtype B-infected individuals have determined that between 40 and 50 percent of AIDS patients can harbour viruses of the SI and, it is presumed, the X4 phenotypes.


title: HIV

text: HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution to West Africa. The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of co-receptor usage (including CD4-independence) may assist the virus in its adaptation to avoid innate restriction factors present in host cells. Adaptation to use normal cellular machinery to enable transmission and productive infection has also aided the establishment of HIV-2 replication in humans. A survival strategy for any infectious agent is not to kill its host, but ultimately become a commensal organism. Having achieved a low pathogenicity, over time, variants that are more successful at transmission will be selected.


title: HIV

text: The HIV virion enters macrophages and CD4 T cells by the adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the target cell membrane and the release of the HIV capsid into the cell.


title: HIV

text: Entry to the cell begins through interaction of the trimeric envelope complex (gp160 spike) on the HIV viral envelope and both CD4 and a chemokine co-receptor (generally either CCR5 or CXCR4, but others are known to interact) on the target cell surface. Gp120 binds to integrin αβ activating LFA-1, the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1. The gp160 spike contains binding domains for both CD4 and chemokine receptors.


title: HIV

text: The first step in fusion involves the high-affinity attachment of the CD4 binding domains of gp120 to CD4. Once gp120 is bound with the CD4 protein, the envelope complex undergoes a structural change, exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor. This allows for a more stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to penetrate the cell membrane. Repeat sequences in gp41, HR1, and HR2 then interact, causing the collapse of the extracellular portion of gp41 into a hairpin shape. This loop structure brings the virus and cell membranes close together, allowing fusion of the membranes and subsequent entry of the viral capsid.


title: HIV

text: After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell. During the microtubule-based transport to the nucleus, the viral single-strand RNA genome is transcribed into double-strand DNA, which is then integrated into a host chromosome.


title: HIV

text: HIV can infect dendritic cells (DCs) by this CD4-CCR5 route, but another route using mannose-specific C-type lectin receptors such as DC-SIGN can also be used. DCs are one of the first cells encountered by the virus during sexual transmission. They are currently thought to play an important role by transmitting HIV to T cells when the virus is captured in the mucosa by DCs. The presence of FEZ-1, which occurs naturally in neurons, is believed to prevent the infection of cells by HIV.


title: HIV

text: HIV-1 entry, as well as entry of many other retroviruses, has long been believed to occur exclusively at the plasma membrane. More recently, however, productive infection by pH-independent, clathrin-mediated endocytosis of HIV-1 has also been reported and was recently suggested to constitute the only route of productive entry.


title: HIV

text: Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the positive-sense single-stranded RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA) molecule. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow the virus to evade the body's immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a sense DNA from the "antisense" cDNA. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus. The integration of the viral DNA into the host cell's genome is carried out by another viral enzyme called integrase.


title: HIV

text: The integrated viral DNA may then lie dormant, in the latent stage of HIV infection. To actively produce the virus, certain cellular transcription factors need to be present, the most important of which is NF-"κ"B (nuclear factor kappa B), which is upregulated when T cells become activated. This means that those cells most likely to be targeted, entered and subsequently killed by HIV are those actively fighting infection.


title: HIV

text: During viral replication, the integrated DNA provirus is transcribed into RNA. The full-length genomic RNAs (gRNA) can be packaged into new viral particles in a pseudodiploid form. The selectivity in the packaging is explained by the structural properties of the dimeric conformer of the gRNA. The gRNA dimer is characterized by a tandem three-way junction within the gRNA monomer, in which the SD and AUG hairpins, responsible for splicing and translation respectively, are sequestered and the DIS (dimerization initiation signal) hairpin is exposed.The formation of the gRNA dimer is mediated by a 'kissing' interaction between the DIS hairpin loops of the gRNA monomers. At the same time, certain guanosine residues in the gRNA are made available for binding of the nucleocapsid (NC) protein leading to the subsequent virion assembly. The labile gRNA dimer has been also reported to achieve a more stable conformation following the NC binding, in which both the DIS and the U5:AUG regions of the gRNA participate in extensive base pairing.


title: HIV

text: RNA can also be processed to produce mature messenger RNAs (mRNAs). In most cases, this processing involves RNA splicing to produce mRNAs that are shorter than the full-length genome. Which part of the RNA is removed during RNA splicing determines which of the HIV protein-coding sequences is translated.


title: HIV

text: Mature HIV mRNAs are exported from the nucleus into the cytoplasm, where they are translated to produce HIV proteins, including Rev. As the newly produced Rev protein is produced it moves to the nucleus, where it binds to full-length, unspliced copies of virus RNAs and allows them to leave the nucleus. Some of these full-length RNAs function as mRNAs that are translated to produce the structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles.


title: HIV

text: HIV-1 and HIV-2 appear to package their RNA differently. HIV-1 will bind to any appropriate RNA. HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself.


title: HIV

text: Two RNA genomes are encapsidated in each HIV-1 particle (see Structure and genome of HIV). Upon infection and replication catalyzed by reverse transcriptase, recombination between the two genomes can occur. Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle the genetic information that is transmitted from parental to progeny genomes.


title: HIV

text: Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral therapy. Recombination may also contribute, in principle, to overcoming the immune defenses of the host. Yet, for the adaptive advantages of genetic variation to be realized, the two viral genomes packaged in individual infecting virus particles need to have arisen from separate progenitor parental viruses of differing genetic constitution. It is unknown how often such mixed packaging occurs under natural conditions.


title: HIV

text: Bonhoeffer "et al." suggested that template switching by reverse transcriptase acts as a repair process to deal with breaks in the single-stranded RNA genome. In addition, Hu and Temin suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of the adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process, the generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching.


title: HIV

text: HIV-1 infection causes chronic inflammation and production of reactive oxygen species. Thus, the HIV genome may be vulnerable to oxidative damage, including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod "et al." suggested that recombination by viruses is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit.


title: HIV

text: The final step of the viral cycle, assembly of new HIV-1 virions, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi apparatus where it is cleaved by furin resulting in the two HIV envelope glycoproteins, gp41 and gp120. These are transported to the plasma membrane of the host cell where gp41 anchors gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. The budded virion is still immature as the gag polyproteins still need to be cleaved into the actual matrix, capsid and nucleocapsid proteins. This cleavage is mediated by the packaged viral protease and can be inhibited by antiretroviral drugs of the protease inhibitor class. The various structural components then assemble to produce a mature HIV virion. Only mature virions are then able to infect another cell.


title: HIV

text: The classical process of infection of a cell by a virion can be called "cell-free spread" to distinguish it from a more recently recognized process called "cell-to-cell spread". In cell-free spread (see figure), virus particles bud from an infected T cell, enter the blood or extracellular fluid and then infect another T cell following a chance encounter. HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread, for which two pathways have been described. Firstly, an infected T cell can transmit virus directly to a target T cell via a virological synapse. Secondly, an antigen-presenting cell (APC), such as a macrophage or dendritic cell, can transmit HIV to T cells by a process that either involves productive infection (in the case of macrophages) or capture and transfer of virions "in trans" (in the case of dendritic cells). Whichever pathway is used, infection by cell-to-cell transfer is reported to be much more efficient than cell-free virus spread. A number of factors contribute to this increased efficiency, including polarised virus budding towards the site of cell-to-cell contact, close apposition of cells, which minimizes fluid-phase diffusion of virions, and clustering of HIV entry receptors on the target cell towards the contact zone. Cell-to-cell spread is thought to be particularly important in lymphoid tissues, where CD4 T cells are densely packed and likely to interact frequently. Intravital imaging studies have supported the concept of the HIV virological synapse "in vivo". The many dissemination mechanisms available to HIV contribute to the virus's ongoing replication in spite of anti-retroviral therapies.


title: HIV

text: HIV differs from many viruses in that it has very high genetic variability. This diversity is a result of its fast replication cycle, with the generation of about 10 virions every day, coupled with a high mutation rate of approximately 3 x 10 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase.


title: HIV

text: This complex scenario leads to the generation of many variants of HIV in a single infected patient in the course of one day. This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. When simultaneous infection occurs, the genome of progeny virions may be composed of RNA strands from two different strains. This hybrid virion then infects a new cell where it undergoes replication. As this happens, the reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes. This recombination is most obvious when it occurs between subtypes.


title: HIV

text: The closely related simian immunodeficiency virus (SIV) has evolved into many strains, classified by the natural host species. SIV strains of the African green monkey (SIVagm) and sooty mangabey (SIVsmm) are thought to have a long evolutionary history with their hosts. These hosts have adapted to the presence of the virus, which is present at high levels in the host's blood, but evokes only a mild immune response, does not cause the development of simian AIDS, and does not undergo the extensive mutation and recombination typical of HIV infection in humans.


title: HIV

text: In contrast, when these strains infect species that have not adapted to SIV ("heterologous" or similar hosts such as rhesus or cynomologus macaques), the animals develop AIDS and the virus generates genetic diversity similar to what is seen in human HIV infection. Chimpanzee SIV (SIVcpz), the closest genetic relative of HIV-1, is associated with increased mortality and AIDS-like symptoms in its natural host. SIVcpz appears to have been transmitted relatively recently to chimpanzee and human populations, so their hosts have not yet adapted to the virus. This virus has also lost a function of the "nef" gene that is present in most SIVs. For non-pathogenic SIV variants, "nef" suppresses T cell activation through the CD3 marker. "Nef" function in non-pathogenic forms of SIV is to downregulate expression of inflammatory cytokines, MHC-1, and signals that affect T cell trafficking. In HIV-1 and SIVcpz, "nef" does not inhibit T-cell activation and it has lost this function. Without this function, T cell depletion is more likely, leading to immunodeficiency.


title: HIV

text: Three groups of HIV-1 have been identified on the basis of differences in the envelope ("env") region: M, N, and O. Group M is the most prevalent and is subdivided into eight subtypes (or clades), based on the whole genome, which are geographically distinct. The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in the phylogenetic tree representing the lineage of the M group of HIV-1. Co-infection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3% were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and the remaining 5.3% were composed of other subtypes and CRFs. Most HIV-1 research is focused on subtype B; few laboratories focus on the other subtypes. The existence of a fourth group, "P", has been hypothesised based on a virus isolated in 2009. The strain is apparently derived from gorilla SIV (SIVgor), first isolated from western lowland gorillas in 2006.


title: HIV

text: HIV-2's closest relative is SIVsm, a strain of SIV found in sooty mangabees. Since HIV-1 is derived from SIVcpz, and HIV-2 from SIVsm, the genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely resembles that of SIVsm.


title: HIV

text: Many HIV-positive people are unaware that they are infected with the virus. For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion is even lower in rural populations. Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results. Again, this proportion is even lower in rural health facilities. Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV.


title: HIV

text: HIV-1 testing is initially done using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a non-reactive result from the initial ELISA are considered HIV-negative, unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate. If the result of either duplicate test is reactive, the specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., a polymerase chain reaction (PCR), western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or PCR or reactive by western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate western blot result, which may be either an incomplete antibody response to HIV in an infected person or nonspecific reactions in an uninfected person.


title: HIV

text: Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. In general, a second specimen should be collected more than a month later and retested for persons with indeterminate western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations. In addition, a few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection.


title: HIV

text: Modern HIV testing is extremely accurate, when the window period is taken into consideration. A single screening test is correct more than 99% of the time. The chance of a false-positive result in a standard two-step testing protocol is estimated to be about 1 in 250,000 in a low risk population. Testing post-exposure is recommended immediately and then at six weeks, three months, and six months.


title: HIV

text: The latest recommendations of the US Centers for Disease Control and Prevention (CDC) show that HIV testing must start with an immunoassay combination test for HIV-1 and HIV-2 antibodies and p24 antigen. A negative result rules out HIV exposure, while a positive one must be followed by an HIV-1/2 antibody differentiation immunoassay to detect which antibodies are present. This gives rise to four possible scenarios:


title: HIV

text: HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.


title: HIV

text: Many governments and research institutions participate in HIV/AIDS research. This research includes behavioral health interventions, such as research into sex education, and drug development, such as research into microbicides for sexually transmitted diseases, HIV vaccines, and anti-retroviral drugs. Other medical research areas include the topics of pre-exposure prophylaxis, post-exposure prophylaxis, circumcision, and accelerated aging effects.


title: HIV

text: The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs. In many parts of the world, HIV has become a chronic condition in which progression to AIDS is increasingly rare.


title: HIV

text: HIV latency, and the consequent viral reservoir in CD4 T cells, dendritic cells, as well as macrophages, is the main barrier to eradication of the virus.


title: HIV

text: It is important to note that although HIV is highly virulent, transmission does not occur through sex when an HIV-positive person has a consistently undetectable viral load (<50 copies/ml) due to anti-retroviral treatment. This was first argued by the Swiss Federal Commission for AIDS/HIV in 2008 in the Swiss Statement, though the statement was controversial at the time. However, following multiple studies, it became clear that the chance of passing on HIV through sex is effectively zero where the HIV-positive person has a consistently undetectable viral load; this is known as U=U, "Undetectable=Untransmittable", also phrased as "can't pass it on". The studies demonstrating U=U are: Opposites Attract, PARTNER 1, PARTNER 2, (for male-male couples) and HPTN052 (for heterosexual couples) when "the partner living with HIV had a durably suppressed viral load." In these studies, couples where one partner was HIV positive and one partner was HIV negative were enrolled and regular HIV testing completed. In total from the four studies, 4097 couples were enrolled over four continents and 151,880 acts of condomless sex were reported; there were zero phylogenetically linked transmissions of HIV where the positive partner had an undetectable viral load. Following this, the U=U consensus statement advocating the use of "zero risk" was signed by hundreds of individuals and organisations, including the US CDC, British HIV Association and "The Lancet" medical journal. The importance of the final results of the PARTNER 2 study were described by the medical director of the Terrence Higgins Trust as "impossible to overstate", while lead author Alison Rodger declared that the message that "undetectable viral load makes HIV untransmittable ... can help end the HIV pandemic by preventing HIV transmission. The authors summarised their findings in "The Lancet" as follows:


title: HIV

text: This result is consistent with the conclusion presented by Anthony S. Fauci, the Director of the National Institute of Allergy and Infectious Diseases for the U.S. National Institutes of Health, and his team in a viewpoint published in the "Journal of the American Medical Association", that U=U is an effective HIV prevention method when an undetectable viral load is maintained.


title: HIV

text: Genital herpes (HSV-2) reactivation in those infected with the virus have an associated increase in CCR-5 enriched CD4+ T cells as well as inflammatory dendritic cells in the submucosa of the genital skin. Tropism of HIV for CCR-5 positive cells explains the two to threefold increase in HIV acquisition among persons with genital herpes. Daily antiviral (e.g. acyclovir) medication do not reduce the sub-clinical post reactivation inflammation and therefore does not confer reduced risk of HIV acquisition.


title: HIV

text: The first news story on "an exotic new disease" appeared May 18, 1981, in the gay newspaper "New York Native".


title: HIV

text: AIDS was first clinically observed in 1981 in the United States. The initial cases were a cluster of injection drug users and gay men with no known cause of impaired immunity who showed symptoms of "Pneumocystis" pneumonia (PCP or PJP, the latter term recognizing that the causative agent is now called "Pneumocystis jirovecii"), a rare opportunistic infection that was known to occur in people with very compromised immune systems. Soon thereafter, researchers at the NYU School of Medicine studied gay men developing a previously rare skin cancer called Kaposi's sarcoma (KS). Many more cases of PJP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC task force was formed to monitor the outbreak. The earliest retrospectively described case of AIDS is believed to have been in Norway beginning in 1966.


title: HIV

text: In the beginning, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus. They also used "Kaposi's Sarcoma and Opportunistic Infections", the name by which a task force had been set up in 1981. In the general press, the term "GRID", which stood for gay-related immune deficiency, had been coined. The CDC, in search of a name and looking at the infected communities, coined "the 4H disease", as it seemed to single out homosexuals, heroin users, hemophiliacs, and Haitians. However, after determining that AIDS was not isolated to the gay community, it was realized that the term GRID was misleading and "AIDS" was introduced at a meeting in July 1982. By September 1982 the CDC started using the name AIDS.


title: HIV

text: In 1983, two separate research groups led by American Robert Gallo and French investigators and Luc Montagnier independently declared that a novel retrovirus may have been infecting AIDS patients, and published their findings in the same issue of the journal "Science". Gallo claimed that a virus his group had isolated from a person with AIDS was strikingly similar in shape to other human T-lymphotropic viruses (HTLVs) his group had been the first to isolate. Gallo admitted in 1987 that the virus he claimed to have discovered in 1984 was in reality a virus sent to him from France the year before. Gallo's group called their newly isolated virus HTLV-III. Montagnier's group isolated a virus from a patient presenting with swelling of the lymph nodes of the neck and physical weakness, two classic symptoms of primary HIV infection. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV). As these two viruses turned out to be the same, in 1986 LAV and HTLV-III were renamed HIV.


title: HIV

text: Another group working contemporaneously with the Montagnier and Gallo groups was that of Jay A. Levy at the University of California, San Francisco. He independently discovered the AIDS virus in 1983 and named it the AIDS associated retrovirus (ARV). This virus was very different from the virus reported by the Montagnier and Gallo groups. The ARV strains indicated, for the first time, the heterogeneity of HIV isolates and several of these remain classic examples of the AIDS virus found in the United States.


title: HIV

text: Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa, and are believed to have transferred to humans (a process known as zoonosis) in the early 20th century.


title: HIV

text: HIV-1 appears to have originated in southern Cameroon through the evolution of SIVcpz, a simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies "Pan troglodytes troglodytes"). The closest relative of HIV-2 is SIVsmm, a virus of the sooty mangabey ("Cercocebus atys atys"), an Old World monkey living in littoral West Africa (from southern Senegal to western Côte d'Ivoire). New World monkeys such as the owl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.


title: HIV

text: HIV-1 is thought to have jumped the species barrier on at least three separate occasions, giving rise to the three groups of the virus, M, N, and O.


title: HIV

text: There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV. However, SIV is a weak virus, and it is typically suppressed by the human immune system within weeks of infection. It is thought that several transmissions of the virus from individual to individual in quick succession are necessary to allow it enough time to mutate into HIV. Furthermore, due to its relatively low person-to-person transmission rate, it can only spread throughout the population in the presence of one or more high-risk transmission channels, which are thought to have been absent in Africa prior to the 20th century.


title: HIV

text: Specific proposed high-risk transmission channels, allowing the virus to adapt to humans and spread throughout the society, depend on the proposed timing of the animal-to-human crossing. Genetic studies of the virus suggest that the most recent common ancestor of the HIV-1 M group dates back to circa 1910. Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including different patterns of sexual contact (especially multiple, concurrent partnerships), the spread of prostitution, and the concomitant high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities. While transmission rates of HIV during vaginal intercourse are typically low, they are increased manyfold if one of the partners has a sexually transmitted infection resulting in genital ulcers. Early 1900s colonial cities were notable for their high prevalence of prostitution and genital ulcers to the degree that as of 1928 as many as 45% of female residents of eastern Leopoldville (currently Kinshasa) were thought to have been prostitutes and as of 1933 around 15% of all residents of the same city were infected by one of the forms of syphilis.


title: HIV

text: The earliest, well-documented case of HIV in a human dates back to 1959 in the Belgian Congo. The virus may have been present in the United States as early as the mid- to late 1960s, as a sixteen-year-old male named Robert Rayford presented with symptoms in 1966 and died in 1969.


title: HIV

text: An alternative and likely complementary hypothesis points to the widespread use of unsafe medical practices in Africa during years following World War II, such as unsterile reuse of single-use syringes during mass vaccination, antibiotic, and anti-malaria treatment campaigns. Research on the timing of most recent common ancestor for HIV-1 groups M and O, as well as on HIV-2 groups A and B, indicates that SIV has given rise to transmissible HIV lineages throughout the twentieth century. The dispersed timing of these transmissions to humans implies that no single external factor is needed to explain the cross-species transmission of HIV. This observation is consistent with both of the two prevailing views of the origin of the HIV epidemics, namely SIV transmission to humans during the slaughter or butchering of infected primates, and the colonial expansion of sub-Saharan African cities.


title: Louisiana Purchase

text: The Louisiana Purchase () was the acquisition of the territory of Louisiana by the United States from the French First Republic in 1803. In return for fifteen million dollars, or approximately eighteen dollars per square mile, the United States nominally acquired a total of in Middle America. However, France only controlled a small fraction of this area, most of which was inhabited by Native Americans; effectively, for the majority of the area, the United States bought the "preemptive" right to obtain "Indian" lands by treaty or by conquest, to the exclusion of other colonial powers.


title: Louisiana Purchase

text: The Kingdom of France had controlled the Louisiana territory from 1699 until it was ceded to Spain in 1762. In 1800, Napoleon, the First Consul of the French Republic, regained ownership of Louisiana as part of a broader effort to re-establish a French colonial empire in North America. However, France's failure to suppress a revolt in Saint-Domingue, coupled with the prospect of renewed warfare with the United Kingdom, prompted Napoleon to consider selling Louisiana to the United States. Acquisition of Louisiana was a long-term goal of President Thomas Jefferson, who was especially eager to gain control of the crucial Mississippi River port of New Orleans. Jefferson tasked James Monroe and Robert R. Livingston with purchasing New Orleans. Negotiating with French Treasury Minister François Barbé-Marbois, the American representatives quickly agreed to purchase the entire territory of Louisiana after it was offered. Overcoming the opposition of the Federalist Party, Jefferson and Secretary of State James Madison persuaded Congress to ratify and fund the Louisiana Purchase.


title: Louisiana Purchase

text: The Louisiana Purchase extended United States sovereignty across the Mississippi River, nearly doubling the nominal size of the country. The purchase included land from fifteen present U.S. states and two Canadian provinces, including the entirety of Arkansas, Missouri, Iowa, Oklahoma, Kansas, and Nebraska; large portions of North Dakota and South Dakota; the area of Montana, Wyoming, and Colorado east of the Continental Divide; the portion of Minnesota west of the Mississippi River; the northeastern section of New Mexico; northern portions of Texas; New Orleans and the portions of the present state of Louisiana west of the Mississippi River; and small portions of land within Alberta and Saskatchewan. At the time of the purchase, the territory of Louisiana's non-native population was around 60,000 inhabitants, of whom half were enslaved Africans. The western borders of the purchase were later settled by the 1819 Adams–Onís Treaty with Spain, while the northern borders of the purchase were adjusted by the Treaty of 1818 with Britain.


title: Louisiana Purchase

text: Throughout the second half of the 18th century, the French colony of Louisiana became a pawn for European political intrigue. The colony was the most substantial presence of France's overseas empire, with other possessions consisting of a few small settlements along the Mississippi and other main rivers. France ceded the territory to Spain in 1762 in the secret Treaty of Fontainebleau. Following French defeat in the Seven Years' War, Spain gained control of the territory west of the Mississippi, and the British received the territory to the east of the river.


title: Louisiana Purchase

text: Following the establishment of the United States, the Americans controlled the area east of the Mississippi and north of New Orleans. The main issue for the Americans was free transit of the Mississippi out to sea. As the lands were being gradually settled by American migrants, many Americans, including Jefferson, assumed that the territory would be acquired "piece by piece." The risk of another power taking it from a weakened Spain made a "profound reconsideration" of this policy necessary. New Orleans was already important for shipping agricultural goods to and from the areas of the United States west of the Appalachian Mountains. Pinckney's Treaty, signed with Spain on October 27, 1795, gave American merchants "right of deposit" in New Orleans, granting them use of the port to store goods for export. The treaty also recognized American rights to navigate the entire Mississippi, which had become vital to the growing trade of the western territories.


title: Louisiana Purchase

text: In 1798, Spain revoked the treaty allowing American use of New Orleans, greatly upsetting Americans. In 1801, Spanish Governor Don Juan Manuel de Salcedo took over from the Marquess of Casa Calvo, and restored the American right to deposit goods. However, in 1800 Spain had ceded the Louisiana territory back to France as part of Napoleon's secret Third Treaty of San Ildefonso. The territory nominally remained under Spanish control, until a transfer of power to France on November 30, 1803, just three weeks before the formal cession of the territory to the United States on December 20, 1803.


title: Louisiana Purchase

text: While the transfer of the territory by Spain back to France in 1800 went largely unnoticed, fear of an eventual French invasion spread across America when, in 1801, Napoleon sent a military force to secure New Orleans. Southerners feared that Napoleon would free all the slaves in Louisiana, which could trigger slave uprisings elsewhere. Though Jefferson urged moderation, Federalists sought to use this against Jefferson and called for hostilities against France. Undercutting them, Jefferson threatened an alliance with the United Kingdom, although relations were uneasy in that direction. In 1801, Jefferson supported France in its plan to take back Saint-Domingue (present-day Haiti), which was then under control of Toussaint Louverture after a slave rebellion. Jefferson sent Livingston to Paris in 1801 with the authorization to purchase New Orleans.


title: Louisiana Purchase

text: In January 1802, France sent General Charles Leclerc on an expedition to Saint-Domingue to reassert French control over a colony that had become essentially autonomous under Louverture. Louverture, as a French general, had fended off incursions from other European powers, but had also begun to consolidate power for himself on the island. Before the revolution, France had derived enormous wealth from St. Domingue at the cost of the lives and freedom of the slaves. Napoleon wanted its revenues and productivity for France restored. Alarmed over the French actions and its intention to re-establish an empire in North America, Jefferson declared neutrality in relation to the Caribbean, refusing credit and other assistance to the French, but allowing war contraband to get through to the rebels to prevent France from regaining a foothold.


title: Louisiana Purchase

text: In 1803, Pierre Samuel du Pont de Nemours, a French nobleman, began to help negotiate with France at the request of Jefferson. Du Pont was living in the United States at the time and had close ties to Jefferson as well as the prominent politicians in France. He engaged in back-channel diplomacy with Napoleon on Jefferson's behalf during a visit to France and originated the idea of the much larger Louisiana Purchase as a way to defuse potential conflict between the United States and Napoleon over North America.


title: Louisiana Purchase

text: Throughout this time, Jefferson had up-to-date intelligence on Napoleon's military activities and intentions in North America. Part of his evolving strategy involved giving du Pont some information that was withheld from Livingston. Desperate to avoid possible war with France, Jefferson sent James Monroe to Paris in 1803 to negotiate a settlement, with instructions to go to London to negotiate an alliance if the talks in Paris failed. Spain procrastinated until late 1802 in executing the treaty to transfer Louisiana to France, which allowed American hostility to build. Also, Spain's refusal to cede Florida to France meant that Louisiana would be indefensible. Monroe had been formally expelled from France on his last diplomatic mission, and the choice to send him again conveyed a sense of seriousness.


title: Louisiana Purchase

text: Napoleon needed peace with the United Kingdom to take possession of Louisiana. Otherwise, Louisiana would be an easy prey for a potential invasion from Britain or the U.S. But in early 1803, continuing war between France and the UK seemed unavoidable. On March 11, 1803, Napoleon began preparing to invade Great Britain.


title: Louisiana Purchase

text: In Saint-Domingue, Leclerc's forces took Louverture prisoner, but their expedition soon faltered in the face of fierce resistance and disease. By early 1803, Napoleon decided to abandon his plans to rebuild France's New World empire. Without sufficient revenues from sugar colonies in the Caribbean, Louisiana had little value to him. Spain had not yet completed the transfer of Louisiana to France, and war between France and the UK was imminent. Out of anger towards Spain and the unique opportunity to sell something that was useless and not truly his yet, Napoleon decided to sell the entire territory.


title: Louisiana Purchase

text: Although the foreign minister Talleyrand opposed the plan, on April 10, 1803, Napoleon told the Treasury Minister François Barbé-Marbois that he was considering selling the entire Louisiana Territory to the United States. On April 11, 1803, just days before Monroe's arrival, Barbé-Marbois offered Livingston all of Louisiana for $15 million, which averages to less than three cents per acre (7¢/ha). The total of $15 million is equivalent to about $ million in dollars, or ( / * 100) round 0 cents per acre. The American representatives were prepared to pay up to $10 million for New Orleans and its environs but were dumbfounded when the vastly larger territory was offered for $15 million. Jefferson had authorized Livingston only to purchase New Orleans. However, Livingston was certain that the United States would accept the offer.


title: Louisiana Purchase

text: The Americans thought that Napoleon might withdraw the offer at any time, preventing the United States from acquiring New Orleans, so they agreed and signed the Louisiana Purchase Treaty on April 30, 1803, (10 Floréal XI in the French Republican calendar) at the Hôtel Tubeuf in Paris. The signers were Robert Livingston, James Monroe, and François Barbé-Marbois. After the signing Livingston famously stated, "We have lived long, but this is the noblest work of our whole lives... From this day the United States take their place among the powers of the first rank." On July 4, 1803, the treaty was announced, but the documents did not arrive in Washington, D.C. until July 14. The Louisiana Territory was vast, stretching from the Gulf of Mexico in the south to Rupert's Land in the north, and from the Mississippi River in the east to the Rocky Mountains in the west. Acquiring the territory doubled the size of the United States.


title: Louisiana Purchase

text: In November 1803, France withdrew its 7,000 surviving troops from Saint-Domingue (more than two-thirds of its troops died there) and gave up its ambitions in the Western Hemisphere. In 1804 Haiti declared its independence; but fearing a slave revolt at home, Jefferson and the rest of Congress refused to recognize the new republic, the second in the Western Hemisphere, and imposed a trade embargo against it. This, together with the successful French demand for an indemnity of 150 million francs in 1825, severely hampered Haiti's ability to repair its economy after decades of war.


title: Louisiana Purchase

text: After Monroe and Livingston had returned from France with news of the purchase, an official announcement of the purchase was made on July 4, 1803. This gave Jefferson and his cabinet until October, when the treaty had to be ratified, to discuss the constitutionality of the purchase. Jefferson considered a constitutional amendment to justify the purchase; however, his cabinet convinced him otherwise. Jefferson justified the purchase by rationalizing, "it is the case of a guardian, investing the money of his ward in purchasing an important adjacent territory; & saying to him when of age, I did this for your good." Jefferson ultimately came to the conclusion before the ratification of the treaty that the purchase was to protect the citizens of the United States therefore making it constitutional.


title: Louisiana Purchase

text: Henry Adams and other historians have argued that Jefferson acted hypocritically with the Louisiana Purchase, because of his position as a strict constructionist regarding the Constitution since he stretched the intent of that document to justify his purchase. The American purchase of the Louisiana territory was not accomplished without domestic opposition. Jefferson's philosophical consistency was in question because of his strict interpretation of the Constitution. Many people believed that he and others, including James Madison, were doing something they surely would have argued against with Alexander Hamilton. The Federalists strongly opposed the purchase, favoring close relations with Britain over closer ties to Napoleon.


title: Louisiana Purchase

text: Both Federalists and Jeffersonians were concerned over the purchase's constitutionality. Many members of the House of Representatives opposed the purchase. Majority Leader John Randolph led the opposition. The House called for a vote to deny the request for the purchase, but it failed by two votes, 59–57. The Federalists even tried to prove the land belonged to Spain, not France, but available records proved otherwise. The Federalists also feared that the power of the Atlantic seaboard states would be threatened by the new citizens in the West, whose political and economic priorities were bound to conflict with those of the merchants and bankers of New England. There was also concern that an increase in the number of slave-holding states created out of the new territory would exacerbate divisions between North and South. A group of Northern Federalists led by Senator Timothy Pickering of Massachusetts went so far as to explore the idea of a separate northern confederacy.


title: Louisiana Purchase

text: Another concern was whether it was proper to grant citizenship to the French, Spanish, and free black people living in New Orleans, as the treaty would dictate. Critics in Congress worried whether these "foreigners", unacquainted with democracy, could or should become citizens.


title: Louisiana Purchase

text: Spain protested the transfer on two grounds: First, France had previously promised in a note not to alienate Louisiana to a third party and second, France had not fulfilled the Third Treaty of San Ildefonso by having the King of Etruria recognized by all European powers. The French government replied that these objections were baseless since the promise not to alienate Louisiana was not in the treaty of San Ildefonso itself and therefore had no legal force, and the Spanish government had ordered Louisiana to be transferred in October 1802 despite knowing for months that Britain had not recognized the King of Etruria in the Treaty of Amiens.


title: Louisiana Purchase

text: Henry Adams claimed "The sale of Louisiana to the United States was trebly invalid; if it were French property, Bonaparte could not constitutionally alienate it without the consent of the French Chambers; if it were Spanish property, he could not alienate it at all; if Spain had a right of reclamation, his sale was worthless." The sale of course was not "worthless"—the U.S. actually did take possession. Furthermore, the Spanish prime minister had authorized the U.S. to negotiate with the French government "the acquisition of territories which may suit their interests." Spain turned the territory over to France in a ceremony in New Orleans on November 30, a month before France turned it over to American officials.


title: Louisiana Purchase

text: Other historians counter the above arguments regarding Jefferson's alleged hypocrisy by asserting that countries change their borders in two ways: (1) conquest, or (2) an agreement between nations, otherwise known as a treaty. The Louisiana Purchase was the latter, a treaty. The Constitution specifically grants the president the power to negotiate treaties (Art. II, Sec. 2), which is just what Jefferson did.


title: Louisiana Purchase

text: Madison (the "Father of the Constitution") assured Jefferson that the Louisiana Purchase was well within even the strictest interpretation of the Constitution. Treasury Secretary Albert Gallatin added that since the power to negotiate treaties was specifically granted to the president, the only way extending the country's territory by treaty could "not" be a presidential power would be if it were specifically excluded by the Constitution (which it was not). Jefferson, as a strict constructionist, was right to be concerned about staying within the bounds of the Constitution, but felt the power of these arguments and was willing to "acquiesce with satisfaction" if the Congress approved the treaty. The Senate quickly ratified the treaty, and the House, with equal readiness, authorized the required funding, as the Constitution specifies. The fledgling United States did not have $15 million in its treasury; it borrowed the sum from Great Britain, at an annual interest rate of six percent. The United States Senate advised and consented to ratification of the treaty with a vote of twenty-four to seven on October 20. On the following day, October 21, 1803, the Senate authorized Jefferson to take possession of the territory and establish a temporary military government. In legislation enacted on October 31, Congress made temporary provisions for local civil government to continue as it had under French and Spanish rule and authorized the President to use military forces to maintain order. Plans were also set forth for several missions to explore and chart the territory, the most famous being the Lewis and Clark Expedition.


title: Louisiana Purchase

text: The opposition of New England Federalists to the Louisiana Purchase was primarily economic self-interest, not any legitimate concern over constitutionality or whether France indeed owned Louisiana or was required to sell it back to Spain should it desire to dispose of the territory. The Northerners were not enthusiastic about Western farmers gaining another outlet for their crops that did not require the use of New England ports. Also, many Federalists were speculators in lands in upstate New York and New England and were hoping to sell these lands to farmers, who might go west instead, if the Louisiana Purchase went through. They also feared that this would lead to Western states being formed, which would likely be Republican, and dilute the political power of New England Federalists.


title: Louisiana Purchase

text: When Spain later objected to the United States purchasing Louisiana from France, Madison responded that America had first approached Spain about purchasing the property but had been told by Spain itself that America would have to treat with France for the territory.


title: Louisiana Purchase

text: France turned over New Orleans, the historic colonial capital, on December 20, 1803, at the Cabildo, with a flag-raising ceremony in the Plaza de Armas, now Jackson Square. Just three weeks earlier, on November 30, 1803, Spanish officials had formally conveyed the colonial lands and their administration to France.


title: Louisiana Purchase

text: On March 9 and 10, 1804, another ceremony, commemorated as Three Flags Day, was conducted in St. Louis, to transfer ownership of Upper Louisiana from Spain to France, and then from France to the United States. From March 10 to September 30, 1804, Upper Louisiana was supervised as a military district, under its first civil commandant, Amos Stoddard, who was appointed by the War Department.


title: Louisiana Purchase

text: Effective October 1, 1804, the purchased territory was organized into the Territory of Orleans (most of which would become the state of Louisiana) and the District of Louisiana, which was temporarily under control of the governor and judicial system of the Indiana Territory. The following year, the District of Louisiana was renamed the Territory of Louisiana. New Orleans was the administrative capital of the Orleans Territory, and St. Louis was the capital of the Louisiana Territory.


title: Louisiana Purchase

text: To pay for the land, the American government used a mix of sovereign bonds and the assumption of French debts. Earlier in 1803, Francis Baring and Company of London had become the U.S. government's official banking agent in London following the failure of Bird, Savage & Bird. Because of this favored position, the U.S. asked Barings to handle the transaction. Barings had a close relationship with Hope and Company of Amsterdam, and the two banking houses worked together to facilitate and underwrite the purchase. Hopes brought to the transaction experience with issuing sovereign bonds and Barings brought its American connections.


title: Louisiana Purchase

text: Francis Baring son Alexander and Pierre Labouchère from Hopes arrived in Paris in April 1803 to assist with the negotiations. With the bankers' help, the French and American negotiators settled on a price of 80 million francs ($15 million), down from an initial price of 100 million francs, a sum the Americans could not afford and the financers could not provide. In the final agreement, the value of the U.S. currency was set at francs per U.S. dollar. In dollars, the $15 million purchase price is equivalent to $ million.


title: Louisiana Purchase

text: As part of the deal, the U.S. assumed responsibility for 20 million francs ($3.75 million) of French debts owed to U.S. citizens. The remaining 60 million francs ($11.25 million) were financed through U.S. government bonds carrying 6% interest, redeemable between 1819 and 1822. In October 1803, the U.S. Treasury had some $5.86 million in specie on hand, $2 million of which would be used to pay a portion of the debts assumed from France as part of the purchase.


title: Louisiana Purchase

text: Because Napoleon wanted to receive his money as quickly as possible, Barings and Hopes purchased the bonds for 52 million francs, agreeing to an initial 6 million franc payment upon issuance of the bonds followed by 23 monthly payments of 2 million francs each. The first group of bonds were issued on January 16, 1804, but the banks had already provided a 10 million franc advance to France in July 1803. In need of funds, Napoleon pressed the banks to complete their purchase of the bonds as quickly as possible, and by April 1804 the banks transferred an additional 40.35 million francs to fully discharge their obligations to France. In the end, Barings and Hopes acquired the $11.25 million in bonds for just $9.44 million.


title: Louisiana Purchase

text: Although the War of the Third Coalition, which brought France into a war with the United Kingdom, began before the purchase was completed, the British government initially allowed the deal to proceed as it was better for the neutral Americans to own the territory than the hostile French. However by December 1803, the British directed Barings to halt future payments to France. Barings relayed to order to Hopes, which declined to comply, allowing the final payments to be made to France in April 1804.


title: Louisiana Purchase

text: A dispute soon arose between Spain and the United States regarding the extent of Louisiana. The territory's boundaries had not been defined in the 1762 Treaty of Fontainebleau that ceded it from France to Spain, nor in the 1801 Third Treaty of San Ildefonso ceding it back to France, nor the 1803 Louisiana Purchase agreement ceding it to the United States.


title: Louisiana Purchase

text: The U.S. claimed that Louisiana included the entire western portion of the Mississippi River drainage basin to the crest of the Rocky Mountains and land extending to the Rio Grande and West Florida. Spain insisted that Louisiana comprised no more than the western bank of the Mississippi River and the cities of New Orleans and St. Louis. The dispute was ultimately resolved by the Adams–Onís Treaty of 1819, with the United States gaining most of what it had claimed in the west.


title: Louisiana Purchase

text: The relatively narrow Louisiana of New Spain had been a special province under the jurisdiction of the Captaincy General of Cuba, while the vast region to the west was in 1803 still considered part of the Commandancy General of the Provincias Internas. Louisiana had never been considered one of New Spain's internal provinces. If the territory included all the tributaries of the Mississippi on its western bank, the northern reaches of the purchase extended into the equally ill-defined British possession—Rupert's Land of British North America, now part of Canada. The purchase originally extended just beyond the 50th parallel. However, the territory north of the 49th parallel (including the Milk River and Poplar River watersheds) was ceded to the UK in exchange for parts of the Red River Basin south of 49th parallel in the Anglo-American Convention of 1818.


title: Louisiana Purchase

text: The eastern boundary of the Louisiana purchase was the Mississippi River, from its source to the 31st parallel, though the source of the Mississippi was, at the time, unknown. The eastern boundary below the 31st parallel was unclear. The U.S. claimed the land as far as the Perdido River, and Spain claimed that the border of its Florida Colony remained the Mississippi River. The Adams–Onís Treaty with Spain resolved the issue upon ratification in 1821. Today, the 31st parallel is the northern boundary of the western half of the Florida Panhandle, and the Perdido is the western boundary of Florida.


title: Louisiana Purchase

text: Because the western boundary was contested at the time of the purchase, President Jefferson immediately began to organize four missions to explore and map the new territory. All four started from the Mississippi River. The Lewis and Clark Expedition (1804) traveled up the Missouri River; the Red River Expedition (1806) explored the Red River basin; the Pike Expedition (1806) also started up the Missouri but turned south to explore the Arkansas River watershed. In addition, the Dunbar–Hunter Expedition (1804–1805) explored the Ouachita River watershed. The maps and journals of the explorers helped to define the boundaries during the negotiations leading to the Adams–Onís Treaty, which set the western boundary as follows: north up the Sabine River from the Gulf of Mexico to its intersection with the 32nd parallel, due north to the Red River, up the Red River to the 100th meridian, north to the Arkansas River, up the Arkansas River to its headwaters, due north to the 42nd parallel and due west to its previous boundary.


title: Louisiana Purchase

text: Governing the Louisiana Territory was more difficult than acquiring it. Its European peoples, of ethnic French, Spanish and Mexican descent, were largely Catholic; in addition, there was a large population of enslaved Africans made up of a high proportion of recent arrivals, as Spain had continued the transatlantic slave trade. This was particularly true in the area of the present-day state of Louisiana, which also contained a large number of free people of color. Both present-day Arkansas and Missouri already had some slaveholders in the 18th and early 19th century.


title: Louisiana Purchase

text: During this period, south Louisiana received an influx of French-speaking refugee planters, who were permitted to bring their slaves with them, and other refugees fleeing the large slave revolt in Saint-Domingue. Many Southern slaveholders feared that acquisition of the new territory might inspire American-held slaves to follow the example of those in Saint-Domingue and revolt. They wanted the U.S. government to establish laws allowing slavery in the newly acquired territory so they could be supported in taking their slaves there to undertake new agricultural enterprises, as well as to reduce the threat of future slave rebellions.


title: Louisiana Purchase

text: The Louisiana Territory was broken into smaller portions for administration, and the territories passed slavery laws similar to those in the southern states but incorporating provisions from the preceding French and Spanish rule (for instance, Spain had prohibited slavery of Native Americans in 1769, but some slaves of mixed African-Native American descent were still being held in St. Louis in Upper Louisiana when the U.S. took over). In a freedom suit that went from Missouri to the U.S. Supreme Court, slavery of Native Americans was finally ended in 1836. The institutionalization of slavery under U.S. law in the Louisiana Territory contributed to the American Civil War a half century later. As states organized within the territory, the status of slavery in each state became a matter of contention in Congress, as southern states wanted slavery extended to the west, and northern states just as strongly opposed new states being admitted as "slave states." The Missouri Compromise of 1820 was a temporary solution.


title: Louisiana Purchase

text: After the early explorations, the U.S. government sought to establish control of the region, since trade along the Mississippi and Missouri rivers was still dominated by British and French traders from Canada and allied Indians, especially the Sauk and Fox. The U.S. adapted the former Spanish facility at Fort Bellefontaine as a fur trading post near St. Louis in 1804 for business with the Sauk and Fox. In 1808 two military forts with trading factories were built, Fort Osage along the Missouri River in western present-day Missouri and Fort Madison along the Upper Mississippi River in eastern present-day Iowa. With tensions increasing with Great Britain, in 1809 Fort Bellefontaine was converted to a U.S. military fort and was used for that purpose until 1826.


title: Louisiana Purchase

text: During the War of 1812, Great Britain hoped to annex all or at least portions of the Louisiana Purchase should they successfully defeat the U.S. Aided by their Indian allies, the British defeated U.S. forces in the Upper Mississippi; the U.S. abandoned Forts Osage and Madison, as well as several other U.S. forts built during the war, including Fort Johnson and Fort Shelby. U.S. ownership of the whole Louisiana Purchase region was confirmed in the Treaty of Ghent (ratified in February 1815) and guaranteed on the battlefield at the decisive Battle of New Orleans when the British sent over 10,000 of the best British Army soldiers to try to take New Orleans in a 5 month long campaign starting from September 1814 (First Battle of Fort Bowyer) to February 1815 (Second Battle of Fort Bowyer). Nobody really knows what post-victory plans for New Orleans and Upper Louisiana were given by the British government to Major General Sir Edward Pakenham and his second-in-command Major General Samuel Gibbs because both generals were killed in action at the Battle of New Orleans. Pakenham was ordered to conduct the New Orleans/Mobile campaign even in the middle of the peace negotiations in late 1814. The British would have likely garrisoned New Orleans and would have occupied it for a very long time because they and their ally Spain did not recognize any treaties and land deals conducted by Napoleon since 1800, especially the Louisiana Purchase. The U.S. later built or expanded forts along the Mississippi and Missouri rivers, including adding to Fort Bellefontaine, and constructing Fort Armstrong (1816) and Fort Edwards (1816) in Illinois, Fort Crawford (1816) in Wisconsin, Fort Snelling (1819) in Minnesota, and Fort Atkinson (1819) in Nebraska.


title: Louisiana Purchase

text: The Louisiana Purchase was negotiated between France and the United States, without consulting the various Indian tribes who lived on the land and who had not ceded the land to any colonial power. The four decades following the Louisiana Purchase was an era of court decisions removing many tribes from their lands east of the Mississippi for resettlement in the new territory, culminating in the Trail of Tears.


title: Louisiana Purchase

text: The purchase of the Louisiana Territory led to debates over the idea of indigenous land rights that persisted into the mid 20th century. The many court cases and tribal suits in the 1930s for historical damages flowing from the Louisiana Purchase led to the Indian Claims Commission Act (ICCA) in 1946. Felix S. Cohen, Interior Department Lawyer who helped pass ICCA, is often quoted as saying, "practically all of the real estate acquired by the United States since 1776 was purchased not from Napoleon or any other emperor or czar but from its original Indian owners", roughly estimating that Indians had received twenty times as much as France had for the territory bought by the United States, "somewhat in excess of 800 million dollars". More recently, the total cost to the U.S. government of all subsequent treaties and financial settlements over the land has been estimated to be around 2.6 billion dollars.


title: Ian McShane

text: Ian David McShane (born 29 September 1942) is an English actor, producer and director. He is known for his television performances, particularly as the title role in the BBC series "Lovejoy" (1986–1994), Al Swearengen in "Deadwood" (2004–2006) and its , as well as Mr. Wednesday in "American Gods" (2017–2021). For the original series of "Deadwood", McShane won the Golden Globe Award for Best Actor – Television Series Drama and received a nomination for the Primetime Emmy Award for Outstanding Lead Actor in a Drama Series; for the film, he (as producer) was nominated for the Primetime Emmy Award for Outstanding Television Movie.


title: Ian McShane

text: His film roles include Harry Brown in "The Wild and the Willing" (1962), Charlie Cartwright in "If It's Tuesday, This Must Be Belgium" (1969), Wolfe Lissner in "Villain" (1971), Teddy Bass in "Sexy Beast" (2000), Frank Powell in "Hot Rod" (2007), Captain Hook in "Shrek the Third" (2007), Tai Lung in "Kung Fu Panda" (2008), Blackbeard in "" (2011) and Winston Scott in the "John Wick" film series (2014–present).


title: Ian McShane

text: McShane was born Ian David McShane in Blackburn, Lancashire, on 29 September 1942, the only child of Irene ("née" Cowley; 1921–2021) and professional footballer Harry McShane (1920–2012). His father was Scottish, from Holytown, Lanarkshire, and his mother, who was born in England, was of Irish and English descent. McShane grew up in Davyhulme, Lancashire, and attended Stretford Grammar School. After being a member of the National Youth Theatre, he studied at the Royal Academy of Dramatic Art (RADA), alongside Anthony Hopkins and John Hurt. McShane shared a flat with Hurt, whom he called his "oldest friend in the business", and was still a student at RADA when he appeared (along with Hurt) in his first film "The Wild and the Willing" (1962). He went on to play Satan in the York Mystery Plays in 1963.


title: Ian McShane

text: In the United Kingdom, McShane's best known role is antiques dealer Lovejoy in the eponymous series. Long before "Lovejoy", McShane was a pin-up as a result of appearances in television series, such as "Wuthering Heights" (1967, as Heathcliff), "Jesus of Nazareth" (1977, as Judas Iscariot), and "Disraeli" (1978)—as well as films like "Sky West and Crooked" (1965) and "Battle of Britain" (1969). The actor also enjoyed success in the United States as British film director Don Lockwood in "Dallas".


title: Ian McShane

text: In the United States, he is known for the role of historical figure Al Swearengen in the HBO series "Deadwood", for which he won the 2005 Golden Globe Award for Best Actor in a Television Drama. He was also nominated at the 2005 Emmy Award and Screen Actors Guild Awards.


title: Ian McShane

text: Among science fiction fans, McShane is known for playing the character Robert Bryson in "". In a 2004 interview with "The Independent", McShane stated that he wished that he had turned down the role of Bryson as he had struggled with the technical dialogue and found looking at Martin Sheen, who was wearing an eye in the middle of his forehead, to be the most embarrassing experience that he had ever had while acting.


title: Ian McShane

text: In 1985, he appeared as an MC on Grace Jones' "Slave to the Rhythm", a concept album which featured his narration interspersed throughout and which sold over a million copies worldwide.


title: Ian McShane

text: His other roles include that of armed robber and gangland boss Jack Last in the "Minder" episode "The Last Video Show." As Captain Hook in "Shrek the Third", Ragnar Sturlusson in "The Golden Compass", Tai Lung in "Kung Fu Panda" (for which he received an Annie Award nomination), and Mr. Bobinsky in "Coraline". In live-action, he has performed in "Hot Rod", the action/thriller "Death Race", and "The Seeker". He has appeared in "The West Wing" as a Russian diplomat. During 2007–08, he starred as Max in the 40th anniversary Broadway revival of Harold Pinter's "The Homecoming", co-starring Eve Best, Raúl Esparza, and Michael McKean, and directed by Daniel Sullivan, at the Cort Theatre (16 December 2007 – 13 April 2008).


title: Ian McShane

text: In 2009, he appeared in "Kings", which was based on the biblical story of David. His portrayal of King Silas Benjamin, an analogue of King Saul, was highly praised with one critic saying: "Whenever "Kings" seems to falter, McShane appears to put bite marks all over the scenery."


title: Ian McShane

text: In 2010, McShane starred in "The Pillars of the Earth" as Bishop Waleran Bigod. The series was a historical drama set in 12th-century England and adapted from Ken Follett's novel of the same name. That same year, the Walt Disney Company confirmed that McShane would portray Blackbeard in "".


title: Ian McShane

text: Since 2010, McShane has narrated the opening teases for each round of ESPN's coverage of The Open Championship. In 2012, McShane had a guest role for two episodes as Murder Santa, a sadistic serial killer in the 1960s in the of "American Horror Story". In 2016, he joined the cast of "Game of Thrones" in Season 6 as Ray.


title: Ian McShane

text: McShane announced on 20 April 2017 that a script for a two-hour "Deadwood" movie had been submitted by creator David Milch to HBO and that a film was as close as ever to happening. "[A] two-hour movie script has been delivered to HBO. If they don't deliver [a finished product], blame them," McShane said. began production in October 2018. "" was released on 31 May 2019, concluding the story of the series.


title: Ian McShane

text: McShane married and divorced Suzan Farmer in the 1960s. Then he married model Ruth Post with whom he had two children, Kate and Morgan. In 1977, he began a relationship with Sylvia Kristel after meeting her on the set of "The Fifth Musketeer". On 30 August 1980, McShane married Gwen Humble. They live in Venice, California. Through his daughter Kate, McShane has three grandchildren.


title: Indian Armed Forces

text: The Indian Armed Forces are the military forces of the Republic of India. It consists of three professional uniformed services: the Indian Army, Indian Navy, and Indian Air Force. Additionally, the Indian Armed Forces are supported by the Central Armed Police Forces, Assam Rifles, Indian Coast Guard and Special Frontier Force and various inter-service commands and institutions such as the Strategic Forces Command, the Andaman and Nicobar Command and the Integrated Defence Staff. The President of India is the Supreme Commander of the Indian Armed Forces but the executive authority and responsibility for national security is vested in the Prime Minister of India and their chosen Cabinet Ministers. The Indian Armed Forces are under the management of the Ministry of Defence of the Government of India. With strength of over 1.4 million active personnel, it is the world's second-largest military force and has the world's largest volunteer army. It also has the third-largest defence budget in the world. The Global Firepower Index report lists it as the fourth most-powerful military.


title: Indian Armed Forces

text: The Indian Armed Forces have been engaged in a number of major military operations, including: the Indo-Pakistani wars of 1947, 1965 and 1971, the Portuguese-Indian War, the Sino-Indian War, the 1967 Cho La incident, the 1987 Sino-Indian skirmish, the Kargil War, and the Siachen conflict among others. India honours its armed forces and military personnel annually on Armed Forces Flag Day, 7 December. Armed with the nuclear triad, the Indian armed forces are steadily undergoing modernisation, with investments in areas such as futuristic soldier systems and missile defence systems.


title: Indian Armed Forces

text: The Department of Defence Production of the Ministry of Defence is responsible for the indigenous production of equipment used by the Indian Armed Forces. It comprises 16 Defence PSUs namely: HAL, BEL, BEML, BDL, MDL, GSL, GRSE, Midhani, AWEIL, GIL, TCL, AVNL, MIL, YIL and IOL. India remains one of the largest importer of defence equipment with Russia, Israel, France and the United States being the top foreign suppliers of military equipment. The Government of India, as part of the Make in India initiative, seeks to indigenise manufacturing and reduce dependence on imports for defence.


title: Indian Armed Forces

text: India has one of the longest military histories, dating back several millennia. The first reference to armies is found in the Vedas as well as the epics "Ramayana" and "Mahabaratha". Classical Indian texts on archery in particular, and martial arts in general are known as Dhanurveda.


title: Indian Armed Forces

text: Indian maritime history dates back 5,000 years. The first tidal dock is believed to have been built at Lothal around 2300 BC during the Indus Valley civilisation period, near the present day port of Mangrol on the Gujarat coast. The Rig Veda written around 1500 BC, credits Varuna with knowledge of the ocean routes and describes naval expeditions. There is reference to the side wings of a vessel called "Plava", which gives the ship stability in storm conditions. A compass, "Matsya yantra" was used for navigation in the fourth and fifth century AD. The earliest known reference to an organisation devoted to ships in ancient India is in the Mauryan Empire from the 4th century BC. Powerful militaries included those of the: Maurya, Satavahana, Chola, Vijayanagara, Mughal and Maratha empires. Emperor Chandragupta Maurya's mentor and advisor Chanakya's "Arthashastra" devotes a full chapter on the state department of waterways under "navadhyaksha" (Sanskrit for Superintendent of ships) . The term, "nava dvipantaragamanam" (Sanskrit for "sailing to other lands by ships," i.e. exploration) appears in this book in addition to appearing in the Vedic text, "Baudhayana Dharmashastra" as the interpretation of the term, "Samudrasamyanam".


title: Indian Armed Forces

text: Sea lanes between India and neighbouring lands were used for trade for many centuries, and are responsible for the widespread influence of Indian Culture on other societies. The Cholas excelled in foreign trade and maritime activity, extending their influence overseas to China and Southeast Asia. During the 17th and 18th centuries, the Maratha and Kerala fleets were expanded, and became the most powerful Naval Forces in the subcontinent, defeating European navies at various times ("See the Battle of Colachel"). The fleet review of the Maratha navy, at which the ships "Pal" and "Qalbat" participated, took place at the Ratnagiri fort. The Maratha Kanhoji Angre, and Kunjali Marakkar, the Naval chief of Saamoothiri were two notable naval chiefs of the period.


title: Indian Armed Forces

text: The Royal Indian Navy was first established by the British while much of India was under the control of the East India Company. In 1892, it became a maritime component as the Royal Indian Marine (RIM).


title: Indian Armed Forces

text: During World War I the Indian Army contributed a number of divisions and independent brigades to the European, Mediterranean and Middle Eastern theatres of war. One million Indian troops served overseas; 62,000 died and another 67,000 were wounded. In total, 74,187 Indian soldiers died during the war. It fought against the German Empire in German East Africa and on the Western Front. Indian divisions were also sent to Egypt, Gallipoli and nearly 700,000 served in Mesopotamia against the Ottoman Empire.


title: Indian Armed Forces

text: Following WWI, the Indian Armed Forces underwent significant transformation. In 1928, Engineer Sub-lieutenant D. N. Mukherji became the first Indian to receive a commission in the Royal Indian Marine. In 1932, the Indian Air Force was established as an auxiliary air force within RAF India; two years later, the RIM was upgraded to the status of a naval service as the Royal Indian Navy (RIN).


title: Indian Armed Forces

text: Though the gradual "Indianisation" of the officer corps began after WWI, at the outbreak of war in 1939, there were no Indian flag, general or air officers in the armed services. The highest-ranking Indian officers were those serving in the non-combatant Indian Medical Service, who held no rank higher than colonel; in the regular Indian Army, there were no Indian officers above the rank of major. The Royal Indian Navy had no Indian senior line officers and only a single Indian senior engineer officer, while the Indian Air Force had no Indian senior officers in 1939, with the highest-ranking Indian air force officer a flight lieutenant.


title: Indian Armed Forces

text: In World War II, the Indian Army began the war in 1939 with just under 200,000 men. By the end of the war it had become the largest volunteer army in history, rising to over 2.5 million men by August 1945. Serving in divisions of infantry, armour and a fledgling airborne forces, they fought on three continents in Africa, Europe and Asia. The Indian Army fought in Ethiopia against the Italian Army, in Egypt, Libya and Tunisia against both the Italian and German Army, and, after the Italian surrender, against the German Army in Italy. However, the bulk of the Indian Army was committed to fighting the Japanese Army, first during the British defeats in Malaya and the retreat from Burma to the Indian border; later, after resting and refitting for the victorious advance back into Burma, as part of the largest British Empire army ever formed. These campaigns cost the lives of over 36,000 Indian servicemen, while another 34,354 were wounded; 67,340 became prisoners of war. Their valour was recognised with the award of some 4,000 decorations, and 38 members of the Indian Army were awarded the Victoria Cross or the George Cross.


title: Indian Armed Forces

text: The demands of war and increasing recognition that the era of British dominance in the subcontinent was ending increased the pace of "Indianisation." In 1940, Subroto Mukherjee (later the first Indian C-in-C and Chief of the Air Staff) became the first Indian to command an air force squadron and attain the (albeit acting) rank of squadron leader. In July 1941, Indian Medical Service officer Hiraji Cursetji became one of the first Indian officers to be promoted to substantive general officer rank. During the war, several Indian Army officers, notably Kodandera M. Cariappa, S. M. Shrinagesh and Kodandera Subayya Thimayya, all of whom would subsequently command the Indian Army, achieved distinction as the first Indian battalion and brigade commanders. On 1 May 1945, Cariappa became the first Indian officer to be promoted to brigadier.


title: Indian Armed Forces

text: At the end of hostilities in 1945, the Indian Army's officer corps included Indian Medical Service officer Hiraji Cursetji as its sole Indian major-general, one IMS brigadier, three Indian brigadiers in combatant arms and 220 other Indian officers in the temporary or acting ranks of colonel and lieutenant-colonel. From October 1945, the granting of regular commissions in the Indian Armed Forces was restricted to Indians, though provisions were made for the continued secondment of British officers for as long as was deemed necessary. In 1946, sailors of the Royal Indian Navy mutinied on board ships and in shore establishments. A total of 78 ships, 20 shore establishments and 20,000 sailors were involved in the rebellion, which had an impact across India. Indianization of the armed forces nevertheless continued to progress. On 15 May 1947, Subroto Mukherjee became the first Indian air officer with the acting rank of air commodore, in the appointment of Deputy Assistant to the Air Officer Commanding (Administration). On 21 July, H.M.S. Choudhry and Bhaskar Sadashiv Soman, both of whom would eventually command the Pakistani and Indian Navies, respectively, became the first Indian Royal Indian Navy officers to be promoted to acting captain. On 30 July, Brigadiers K.M. Cariappa, Muhammad Akbar Khan and Maharaj Shri Rajendrasinhji Jadeja were promoted major-generals, the first Indian general officers in a combat arm of the Indian Army.


title: Indian Armed Forces

text: The period immediately following Indian independence was a traumatic time for India and her armed services. Along with the newly independent India, the Indian Armed Forces were forcibly divided between India and Pakistan, with ships, divisions and aircraft allocated to the respective Dominions. Following partition, on 15 August 1947, the Indian Armed Forces comprised:


title: Indian Armed Forces

text: By the end of 1947, there were a total of 13 Indian major-generals and 30 Indian brigadiers, with all three army commands being led by Indian officers by October 1948, at which time only 260 British officers remained in the new Indian Army as advisers or in posts requiring certain technical abilities. With effect from April 1948, the former Viceroy's Commissioned Officers (VCO) were re-designated Junior Commissioned Officers (JCO), the distinction between King's Commissioned Indian Officers (KCIO) and Indian Commissioned Officers (ICO) was abolished and Indian Other Ranks were re-designated as "other ranks."


title: Indian Armed Forces

text: During this period, the armed forces of India were involved in a number of significant military operations, notably the Indo-Pakistani War of 1947 and Operation Polo, the code name of a military operation in September 1948 where the Indian Armed Forces invaded the State of Hyderabad and overthrew its Nizam, annexing the state into the Indian Union. On 15 January 1949, General K. M. Cariappa was appointed the first Indian Commander-in-Chief of the Indian army. In February 1949, the Indian government repealed colonial-era legislation which mandated limits on the recruitment of certain ethnic groups into the armed forces.


title: Indian Armed Forces

text: Upon India becoming a sovereign republic on 26 January 1950, some of the last vestiges of British rule – such as rank badges, imperial crowns, British ensigns and "Royal" monikers – were dropped and replaced with the Indian tricolour and the Lion Capital of Asoka. On 1 April 1951, the remaining units of Imperial Service Troops of the former princely states were integrated with the regular Indian Army, though only a percentage of the former princely states forces were found capable enough to be retained in active service. While India had become a republic, British officers seconded from the British Armed Forces continued to hold senior positions in the Indian Armed Forces into the early 1960s. On 1 April 1954, Air Marshal Subroto Mukherjee became the first Indian Commander-in-Chief of the Indian Air Force. Effective from 1 April 1955, a Parliamentary Act, the "Commanders-In-Chiefs (Change in Designation) Act", re-designated the office of Commander-in-Chief as the Chief of Staff of each branch. Not until 1958 would the last British chief of staff that of the Indian Navy, be succeeded by an Indian. On 22 April of that year, Vice Admiral Ram Dass Katari became the first Indian Chief of Naval Staff. The Chiefs of Staff of the Indian Air Force and the Indian Navy were upgraded to four-star rank on par with the Chief of Army Staff in 1966 and 1968, respectively.


title: Indian Armed Forces

text: In 1961 tensions rose between India and Portugal over the Portuguese-occupied territory of Goa, which India claimed for itself. After Portuguese police cracked down violently on a peaceful, unarmed demonstration for union with India, the Indian government decided to invade and initiated Operation Vijay. A lopsided air, sea, and ground campaign resulted in the speedy surrender of Portuguese forces. Within 36 hours, 451 years of Portuguese colonial rule ended, and Goa was annexed by India.


title: Indian Armed Forces

text: India fought four major wars with its neighbour Pakistan in 1947, 1965, 1971 and 1999, and with China in 1962 and 1967. Indian victory over Pakistan in the 1971 war, helped create the free country of Bangladesh. In the late 1970s and early 1980s, Pakistan began organising tourist expeditions to the Siachen Glacier, disputed territory with India. Irked by this development, in April 1984 India initiated the successful Operation Meghdoot during which it gained control over all of the 70-kilometre (41-mile)-long Siachen Glacier, and all of its tributary glaciers, as well as the three main passes of the Saltoro Ridge immediately west of the glacier—Sia La, Bilafond La, and Gyong La. According to "TIME" magazine, India gained more than of territory as a result of its military operations in Siachen. In 1987 and in 1989 Pakistan attempted to re-take the glacier but was unsuccessful. The conflict ended with Indian Victory. There has been a ceasefire since 2003.


title: Indian Armed Forces

text: The Indian Peace Keeping Force (IPKF) carried out a mission in northern and eastern Sri Lanka in 1987–1990 to disarm the Tamil Tigers under the terms of the Indo-Sri Lanka Accord. It was a difficult battle for the Indian Army, which was not trained for an unconventional war. After losing approximately 1,200 personnel and several T-72 tanks, India ultimately abandoned the mission in consultation with the Sri Lankan government. In what was labelled as Operation Pawan, the Indian Air Force flew about 70,000 sorties to and within Sri Lanka.


title: Indian Armed Forces

text: The beginning of the 21st century saw a reorientation for India on the global stage from a regional role in the subcontinent to a major role in the Indian Ocean region stretching from the Gulf of Aden to the Malacca Strait. India's sphere of influence needs to encompass not just the South Asian Sub-continent, but also the northern Indian Ocean area, from the eastern seaboard of Africa in the west, to the Malacca Straits in the east, and must include Iran, Afghanistan, the Central Asian Republics (CARs), China and Myanmar. India's credibility, as a regional power will be contingent on institutional stability, economic development and military strength, including nuclear deterrence. The long stretches of disputed borders with China and Pakistan, and sizeable areas under their occupation, continue to be major irritants, in spite of the peace processes under-way with both countries.


title: Indian Armed Forces

text: The headquarters of the Indian Armed Forces is in New Delhi, the capital city of India. The President of India serves as the formal Supreme Commander of the Indian Armed Forces, while actual control lies with the executive headed by the Prime Minister of India. The Ministry of Defence (MoD) is the ministry charged with the responsibilities of countering insurgency and ensuring external security of India. General Manoj Mukund Naravane is the Chief of the Army Staff (COAS), Admiral R.Hari Kumar is the Chief of the Naval Staff (CNS) and Air Chief Marshal Vivek Ram Choudhari is the Chief of the Air Staff (CAS).


title: Indian Armed Forces

text: The Indian armed force are split into different groups based on their region of operation. The Indian Army is divided administratively into seven tactical commands, each under the control of different Lieutenant Generals. The Indian Air Force is divided into five operational and two functional commands. Each command is headed by an air officer commanding-in-chief with the rank of air marshal. The Indian Navy operates three commands. Each command is headed by a flag officer commanding-in-chief with the rank of vice admiral. There are two joint commands whose head can belong to any of the three services. These are the Strategic Forces Command and the Andaman and Nicobar Command. The lack of an overall military commander has helped keep the Indian Armed Forces under civilian control, and has prevented the rise of military dictatorships unlike in neighbouring Pakistan.


title: Indian Armed Forces

text: The code of conduct of the Indian military is detailed in a semi-official book called "Customs and Etiquette in the Services", written by retired Major General Ravi Arora, which details how Indian personnel are expected to conduct themselves generally. Arora is an executive editor of the "Indian Military Review".


title: Indian Armed Forces

text: The major deployments of the Indian army constitute the border regions of India, particularly Jammu and Kashmir, Ladakh, and Northeast India, to engage in counter-insurgency and anti-terrorist operations. The major commitments of the Indian Navy constitute patrol missions, anti-piracy operations off the coast of Somalia, the 'Singapore Indian Maritime Bilateral Exercise' with the Republic of Singapore Navy in the Straits of Malacca, maintaining a military presence in Southeast Asias waters, and joint exercises with other countries, such as: Brasil, South Africa, the United States and Japan, France (Varuna naval exercises), the People's Republic of China, the Russian Navy (INDRA naval exercises), and others.