The study generally noted poor financial capacity and low activity tolerance among the participants. Significant changes were noted in all the domains of HRQOL compared between the treatment-naïve patients and the 12 months treatment cohort. In the same manner, the median CD4 cell count and viral load differed significantly between both groups. The treatment-naïve and the 12 months treatment cohorts consistently reported much lower quality of life scores in the level of dependence domain which includes the measures of mobility, activity of daily living, dependence on medication and work capacity. There were little or no associations between the biomedical markers  and HRQOL indicators. However, the quality of life tended to increase with increase in the CD4 cell count. The poor to no association between the biomedical markers and HRQOL indicators show that these cannot be direct proxies of each other and that the CD4 cell count and viral load alone may be inadequate eligibility criteria for social support.This study compared the level of CD4 count, viral load and health-related quality of life (HRQOL) between treatment-naïve AIDS patients and a cohort of people living with HIV who have been on treatment for 12 months. This study is based on a secondary data analysis of the records of 642 people with HIV consisting of 311 treatment-naïve AIDS patients and 331 people with HIV who have been on treatment for 12 months. The study findings are mostly presented in tables and analysed using the  Surrogate measures such as the CD4 count and viral burden have remained the major markers of disease progression and well-being of people living with HIV (PLWH). Such clinical indicators have also been deemed to provide an incomplete view of disease impact . To bridHRQOL studies in HIV have mostly been cross-sectional in nature and focused mainly on issues such as functioning, adherence to treatment and perceptions about HRQOL . The useFew studies have tried to link biomedical markers of the HIV and AIDS disease progression and HRQOL in developing counties in comparison to the number of such studies conducted in developed countries where the health and social support systems are well established. Given that the biomedical and HRQOL markers of HIV infected people also vary over time, there is also a limited record of studies that have examined how both measures change or interact over time. The WHOQOL-HIV instrument has never been tested over time among PLWH to assess its stability and applicability through the bio-psychosocial trajectory of HIV/AIDS. Against this background, this study sought to establish the relationship between the CD4 count, viral burden and HRQOL and their differences among treatment-naïve people with AIDS and people with HIV who have been on treatment for 12 months. The need for this study is heightened by the current dependence on the CD4 cell count and duration on treatment as the eligibility criteria for disability grants in South Africa.This study is based on a secondary data analysis. The database consists of two cohorts made up of 311 treatment-naïve HIV positive people with AIDS defining characteristics and 331 HIV positive individuals who have been on treatment for 12 months. This resulted in a total of 642 records analysed in this study. This study is part of an original study that recruited participants from antiretroviral treatment clinics based in public hospitals. Convenient sampling of participants was used. The adoption of convenient sampling method is due to the absence of a sampling frame to be used for probability sampling methods. The clinics do not have a waiting list for treatment initiation as patients are placed on treatment as soon as they meet the requirement for antiretroviral therapy (ART) treatment initiation. As such, patients who were ready to commence treatment based on the treatment initiation criteria and who may have gone through the treatment readiness assessment and training processes were co-opted into the study.Persons aged 18 years and above living with HIV and AIDS and accessing care in public health facilities were targeted. The treatment-naïve cohort was limited to persons presenting symptoms attributable to or due to complications from HIV infection and being initiated to treatment for the first time and people who have been on treatment for 12 months.HRQOL was measured using the WHOQOL-HIV instrument. The WHOQOL-HIV is made up of 120 questions divided into 6 domains, namely: the physical; psychological; level of dependence; social relationships; environment and spirituality. The health and demographic data, participants’ CD4 counts and viral load were also part of the instrument. The CD4 count and viral loads were collected from patients’ medical records from routinely conducted tests. The instruments were administered in the respective local language of each participant.t-tests and analysis of variance were used to compare the average HRQOL subscale and domain scores between times, key demographic characteristics and the biological markers. To maximize the data of the two cohorts in the study, combined/aggregate analysis of all the cases was also performed. The combined analysis was to augment the results of the changes observed between the two cohorts. Ethical approval for the study was granted by the University of the Witwatersrand Human Research Ethics Committee. The data used for the secondary analysis did not have any personal detail of the study participants and the analyses and the use of data in this study remained cognizant of issues of confidentiality and anonymity.The study data were managed using the Statistical Package for Social Sciences for windows version 18. Basic descriptive analysis of the participants' socio-demographic and quality of life measures was done and compared between the two cohort groups. This was followed by internal consistency assessment using Cronbach's alpha to assess the reliability of the instruments. Student There were 642 cases in the study consisting of 311 treatment-naïve AIDS patients and 331 people with HIV who have been on treatment for a period of 12 months. The majority of the participants, in both groups, were women and people over 36 years of age, married, with children, unemployed and with only primary education. The proportion of the participants who belongs to support group was more than twofold higher among the 12 months treatment cohort when compared to the proportion in a support group among the treatment-naïve AIDS patients. The average age of the treatment-naïve participants was 39.3 years (standard deviation = 9.8), while the average age of participants in 12 months treatment cohort was 40.8 years (standard deviation = 9.7). The average monthly household income of the treatment-naïve was ZAR565.98 (standard deviation = 375.84) and the average monthly household income for the 12 months treatment cohort is R1490.37 (standard deviation = 984.77). Further description of these variables can be found in χ2 = 326.94; p = .000; n = 623). Similarly, the proportion of people with suppressed viral load below 400 copies/ml was more among the 12 months treatment cohort (78.3%) when compared to the 16.3% viral load suppression below 400 copies/ml noted among the treatment-naïve group .The study noted higher CD4 cell count among the 12 months cohort and this is in comparison to the CD4 cell count among the treatment-naïve group. All the treatment-naïve participants had CD4 cell counts below 500 cells/μl, while 15% of the participant in the 12 months treatment cohort had greater than 500 cells/μl. While almost half of the 12 months treatment cohort had CD4 cell count of greater than 350 cells/μl, less than 1% of the treatment-naïve cohort had similar CD4 cell counts  domain.For a better clinical and statistical judgment, the viral load and CD4 cell count were grouped into categories. The viral load was classed as suppressed and unsuppressed using 400 copies/ml as a cut-off point . The CD4The correlation of these categories of biological markers with WHOQOL-HIV domains showed only two notably low associations between the viral load and level of dependence and environmental domains, respectively, among the treatment-naïve group. All the other correlations showed no association.r = .38, p = .000), SRPB  and psychological domains . Despite this, all the correlations were too low to suggest any association  and physical (10.95) domains. On the other hand, the highest mean scores were noted under CD4 cell count of >500 cell/µl under the psychology (14.63) and SRPB domains (14.86).A post hoc test of the aggregate analysis showed the differences in the mean scores within the respective domains of the CD4 cell counts categories. The quality of life score tended to increase with increases in the CD4 cell count category. The differences between consecutive categories were mostly significant.The objective of this study was to establish the relationship between the CD4 count, viral burden and HRQOL and their difference among treatment-naïve people with AIDS and people with HIV who have been on treatment for 12 months. With this, the study showed few weak correlations between CD4 counts and the quality of life measures. Similarly, the viral load suppression status had very low correlation coefficients with the overall quality of life. Another study conducted in South Africa reported similar correlations between quality of life domains and CD4 cell count .In line with this study's findings, Factors similar to the above are known to also affect an individual's rate of progression from HIV to AIDS . The stuThis study also noted marked differences in quality of life between both cohort groups. This finding agrees with studies that have shown such improvements in the perceived quality of life over time (The generally improved HRQOL over time noted by this study regardless of changes in the biomedical measure of disease progression may also be attributed to the natural psychosocial trajectory of HIV/AIDS prompted by treatment initiation and better psychosocial support. This assertion is premised on the model of achieving balance in the event of HIV infection and moves the individual across four stages – of disintegration, renormalizing, coming-to-terms and creating meaning – . Over tiIn conclusion, this study has described the HRQOL of PLWH based on their position in their treatment history and noted the weak to no association between HRQOL indicators and the biomedical markers of HIV/AIDS such as the CD4 cell count and viral load. The study mostly underscores the multiple factors that affect the natural history of HIV/AIDS. Some of such factors are time, treatment and the socio-demographic characteristics of the individual. This proposition is also predicated on the observation that an individual's perceived quality of life and well-being is also defined by similar factors. With all the variations observed in this study, including the differences in the findings of the time specific and combined analyses, one can say that PLWH are highly heterogeneous in terms of clinical manifestations and support requirements and as such should only be grouped together with caution in research studies and intervention programmes. Furthermore, the general prominence of the psychological, environmental and level of dependence domains noted in this and related studies may require a further research to explore their link with the CD4 cell count and viral load.A possible limitation of this study is that it is not a direct follow-up of the treatment-naïve AIDS patients to measure change over time, but it may serve as a good alternative in HIV and AIDS studies. This assertion is based on the expected bio-psychosocial trajectory of HIV and AIDS and the related differentials over time and along the natural history of the disease .


Immune Reconstitution Inflammatory Syndromes (IRIS) are exaggerated pathological inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) due to exuberant immune responses to occult or apparent opportunistic infections or cancers. In view of paucity of studies from Nigeria, we report 3 cases of IRIS presenting as disseminated infections in HIV-1 infected patients initiating HAART. The first case was a previously healthy female who developed disseminated tuberculosis after 4 weeks of regular HAART. Her HAART regimen was continued and she improved after commencement of anti-tuberculosis drugs, with evidence of progressive increase in CD4 cell count. The second case was a HAART-experienced female who stopped her drugs for 4months. Two months after recommencement of her previous HAART regimen, she developed features of disseminated herpes zoster infection, despite evidence of decrease in viral load by 95%. HAART was continued and she recovered completely after receiving valaciclovir tablets and antibiotics. The third patient was a female student who was commenced HAART on account of chronic cough and weight loss. Three months after regular HAART, she developed features of disseminated Kaposi's sarcoma involving the skin, oropharynx and lungs, despite evidence of 42% increase in CD4 cell count. Unfortunately, she rapidly deteriorated and died during the course of management. Clinicians should be alert to the possibility of IRIS in HIV-infected patients initiated or re-initiated on HAART. There is need for future prospective studies determining risk factors for IRIS in HIV-infected patients from Nigeria. Highly active antiretroviral therapy (HAART) suppresses HIV-replication and restores immune function ultimately improving the quality of life and prolonging survival of HIV-infected patients. Unfortunately, during HAART-induced restoration of immune function, some patients may experience an exaggerated pathological inflammatory response termed immune reconstitution inflammatory syndrome (IRIS). IRIS haIn view of prevailing high HIV prevalence and high rate of new infections, as well as increasing access to HAART, many HIV-infected individuals in sub-Saharan Africa are at a risk of developing IRIS on initiating HAART. However, there is still paucity of studies on IRIS from countries such as Nigeria where an estimated 4500 new HIV infections occur yearly and more than 500 000 HIV-infected patients are expected to initiate HAART [3/l, with predominant neutrophils (52%) and lymphocytes (40%). Renal and liver function tests were normal. Standard combination anti-TB drugs by DOTS were commenced along with tablets prednisolone 40mg daily (tapered). Her HAART regimen was continued but Nevirapine was switched for Efavirenz to avoid drug interactions. All symptoms gradually resolved and by the 3rd month on HAART, her CD4 cell count had increased from 15cells/ul to 163cells/ul.A 37-year old housewife was commenced HAART-(Emtricitabine/Tenofovir/Nevirapine) after 1year progressive weight loss and recurrent diarrhoea, without fever or cough or radiological features of pulmonary tuberculosis. Four weeks after regular HAART, she presented with non-productive cough, breathlessness, fever and progressive painful bilateral inflammatory cervical adenopathies. Chest examination was normal. A repeat chest X-ray however, revealed features suggestive of perihilar adenopathies. Histology of biopsied cervical node confirmed tuberculosis-(TB) granuloma. A diagnosis of disseminated TB-(lungs and nodes) secondary to IRIS was made. A full blood count revealed a packed cell volume of 28% and total white cell count of 2.9 X 103/L, with predominant neutrophils (58%) and lymphocytes (35%). Renal function tests were normal. Chest-X-ray revealed bilateral interstitial opacities. Sputum analysis for bacteria including mycobacteria was negative A clinical diagnosis of disseminated herpes zoster infection (skin and lungs) secondary to IRIS was made. Her previous HAART regimen was continued and tablets valaciclovir 1g bd, intravenous ceftriazone 1g daily and analgesics-Diclofenac potassium 50mg bd were commenced, along with dressing of ulcers. She recovered and continues to do well on follow up.A 47-years old previously healthy HIV-1 infected female was recommenced HAART-(Emtricitabine/Tenofovir/Nevirapine) after four months of non-compliance. Two months after re-initiation of regular HAART, she developed high grade fever, cough and painful vesicobullous eruptions extending from the abdomen to the buttocks within the T11- L2 dermatomes . Cough w3/L, with predominant neutrophils (63%) and lymphocytes (26.4%). Sputum microscopy and cytology were negative for AFB and malignant cells respectively. Chest X-ray showed diffuse bilateral alveolar opacities with obliteration of cardiac borders. Skin biopsy confirmed Kaposi's sarcoma but histology of nodal fine needle aspirates revealed non-specific chronic inflammation. A diagnosis of disseminated Kaposi's sarcoma  secondary to IRIS was made. Her previous HAART regimen was continued and anti-tuberculosis drugs were stopped since symptoms did not improve after 2 months of therapy. While being worked up for systemic chemotherapy, she was received tablets prednisolone 60mg daily (tapered), and tablets levofloxacin 500mg daily for empirical coverage of bacterial pneumonia. After an initial improvement, her condition rapidly deteriorated and she died shortly thereafter. Unfortunately, permission for post-mortem was denied on cultural grounds.A 19-years old HIV-1 infected female student was commenced HAART-(Tenofovir/Emtricitabine/Efavirenz) and empirical anti-TB drugs on account of eight months history of recurrent fever and weight loss, and one month history of cough with haemopytsis. After three months on regular HAART and three weeks on anti-TB drugs, she developed papulonodular discoloured skin lesions associated with oedema , painfulThe clinical presentations of our patients are consistent with established case definitions for IRIS , 7. IRISProfound immunosuppression as reflected in low baseline CD4 cell count was a risk factor for IRIS  identifiTo diminish the exuberant inflammatory response and improve recovery, anti-inflammatory drugs such as steroids remain the cornerstone in the management of moderate to severe IRIS . AlthougWe have described three cases of disseminated infections following HAART-induced immune reconstitution in HIV-1 infected adult Nigerians. It is desirable for future studies to investigate the clinical spectrum and risk factors of IRIS in adult Nigerians.


Study 903 was a Phase III randomized double-blind (DB) 3 year study comparing TDF to stavudine (d4T) each in combination with lamivudine (3TC) and efavirenz (EFV) in HIV-1 infected antiretroviral naïve patients. TDF was associated with durable efficacy and safety . A subset of these patients now provides 10 years of longitudinal efficacy and safety data of TDF-containing once-daily HAART.10 c/mL, and mean CD4 count=299 cells/mm3). At OL baseline, 85 subjects  switched from d4T to TDF. The results reflect only the period of TDF exposure.Subjects in Argentina, Brazil, and the Dominican Republic who completed the 3 year DB period of study were eligible to roll-over into an open-label (OL) study (Study 903E) of the once-daily HAART regimen, TDF+3TC+EFV. At DB baseline 86 subjects were randomized to TDF (62% male, 70% white, mean age 33 yrs, mean HIV RNA=4.9 logSee Table 1Antiretroviral-naïve subjects who received TDF-containing once-daily HAART for up to 10 years demonstrated sustained virologic and immunologic benefit, improved limb fat, stable renal function, and their BMD remained stable after a clinically insignificant decrease that occurred during the first year of TDF therapy.


Drug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center  and Johns Hopkins University HIV Clinic  between 1999 and 2005.Participants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care.1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall  and less time on HAART at JHU , but not statistically associated with time on HAART at CCC . NIDU was independently associated with decreased HAART receipt  and less time on HAART  at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period.Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization. The dual global pandemics of substance abuse and HIV threaten not only individual but also public health. Injection drug use (IDU) was the HIV transmission risk factor for 35% of females and 20% of males with AIDS reported through 2007 in the United States (US) The use of highly active antiretroviral therapy (HAART) has led to sustained decreases in HIV-related morbidity and mortality in vitro, and in animals and humans have suggested that cocaine and opiates have direct effects on HIV replication and T cell immunology Behaviors related to drug use and illicit drugs themselves may lead to poorer treatment outcomes and high risk of HIV transmission. Potential effects of drug use include neurocognitive impairment, psychosocial dysfunction, or exacerbation of psychiatric illness. Altered judgment and decision-making may lead to high-risk sexual behavior and attendant risk of acquiring other sexually-transmitted infections, which in turn may facilitate HIV transmission A history of IDU has been associated with delayed initiation of HAART The study was approved by the Vanderbilt University and Johns Hopkins Institutional Review Boards. Exemption from informed consent was approved by the Vanderbilt University Institutional Review Board. Written informed consent was obtained for all participants from Johns Hopkins. To maintain patient confidentiality, non-identifiable patient data were used in the analyses.The overall cohort included persons who had their first outpatient visit at the Vanderbilt-affiliated Comprehensive Care Center (CCC) in Nashville or the Moore Clinic for HIV Care at Johns Hopkins University (JHU) in Baltimore between January 1, 1999 and December 31, 2004. Subjects must have had at least two outpatient visits during the study period. Study follow-up for each patient was censored at the date of death, date of last clinic encounter if the patient met lost-to-follow-up criteria (defined as ≥18 months between clinic encounters without laboratory data during the intervening time), or December 31, 2005 if the last clinic encounter or death date was after that date.The CCC is the largest HIV outpatient care center in Tennessee and includes three satellite clinics in rural Middle Tennessee. In addition to providing specialized HIV medical care, the CCC provides case management and coordination of mental health services including substance abuse treatment programs. Clinical data have been entered directly into an electronic medical record (EMR) since 1997, either by medical providers at the time of the patient encounter, by automated laboratory data upload, or by retrospective entry by clinic personnel . Risk factors for HIV acquisition, including history of IDU, are identified by clinicians at patient enrollment at CCC. Medical charts were reviewed by trained abstractors to ascertain additional history of IDU, NIDU and heavy use or abuse of alcohol (defined below).JHU provides integrated primary and subspecialty care for a large proportion of HIV-infected patients in the Baltimore metropolitan area. An observational, longitudinal, clinical cohort of adult patients receiving HIV care at JHU has been maintained since 1990 Persons from the CCC cohort were categorized into three mutually exclusive groups for analysis: persons with an IDU history, persons with NIDU history, and persons with neither IDU nor NIDU history. The overall cohort (including JHU) was categorized into two groups for analysis: persons with an IDU history and those with no history of IDU. For the CCC cohort, persons were considered to have a history of IDU if there was any record of IDU as self-reported probable route of HIV infection, or any corresponding ICD-9 diagnoses or free text entered into the EMR by providers. For the JHU cohort, IDU as either provider-entered diagnosis or self-reported HIV risk is captured as part of structured data abstraction procedures NIDU at CCC was defined as any record of substance abuse/use, dependence, or addiction, or self-reported heavy alcohol use, or recreational drug use, of any kind or amount, excluding anyone whose HIV risk factor was IDU. After an electronic query of ICD-9 diagnosis codes for abuse and/or dependence identified persons with IDU as HIV risk factor and those with a history of NIDU, chart validation was performed on the remaining persons to assess substance use through notation by the provider of concern about drug or alcohol use, notation of a patient entering a drug or alcohol rehabilitation program, notation of non-injection prescription drug abuse, or indication of medical, legal, or social problems resulting from drug or alcohol use. Drugs used in the diagnosis of NIDU included cocaine, crack cocaine, methamphetamine, heroin, opiates, marijuana, and “party drugs” such as methylenedioxymethamphetamine and nitrous oxide. Alcohol use was categorized as NIDU if there was a provider notation in the chart of heavy alcohol use, or an alcohol-related clinical diagnosis . To account for potential weakness in the pertinence of a history of drug use to the receipt of HAART, additional reviews of charts of persons categorized as having historical IDU and NIDU were conducted at CCC to assess for active drug use during the study period.+ T cell count and plasma HIV-1 RNA level were defined as the first values obtained ≤60 days prior to or any time after the first clinic visit between January 1, 1999 and December 31, 2004.Baseline (enrollment) demographics and laboratory values were obtained from the medical record. Baseline CD4The primary outcomes of interest were ever receiving HAART and cumulative time on HAART during the study period. HAART was defined as (1) at least 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in combination with at least 1 protease inhibitor (PI) and/or non-NRTI (NNRTI); (2) one NRTI and any PI and any NNRTI; or (3) at least 3 NRTIs. Persons who received HAART for ≥ 7 days were classified as having ever received HAART. Time on HAART included cumulative HAART between January 1, 1999 and December 31, 2005, including HAART that began prior to January 1, 1999. HAART start was set at January 1, 1999 if HAART start occurred prior to that date and HAART end date was set as December 31, 2005 if HAART stop occurred after that date. Proportional time on HAART was calculated as cumulative weeks on HAART for each individual who ever received HAART divided by the follow-up time in weeks for that individual. For analyses, this outcome was dichotomized as ≥ or <95% of available follow-up time on HAART 2 or Fisher's exact tests. Continuous variables are shown as medians and were compared with the Wilcoxon rank-sum (Mann-Whitney U) or Kruskal-Wallis tests. Logistic regression models were constructed to analyze receipt of HAART and proportional time on HAART according to drug use category and site of care. Other covariates adjusted for in multivariate analyses included baseline demographics, cumulative follow-up time, CD4+ T cell count categorized as < or ≥200 cells/mm3, and HIV-1 RNA level categorized as ≤ or >5 log10  copies/mL. Separate multivariate logistic regression models were constructed a priori for the CCC and JHU cohort databases. These included identical models without NIDU history (Model 1). A corresponding model to assess the effect of NIDU in the CCC cohort included the same demographic and laboratory variables as the other models as well as IDU and NIDU history (Model 2). Secondary models including active drug use during the study period, instead of historical drug use, were used to assess the association of activity of drug use with receipt of HAART and proportional time on HAART in the CCC cohort. All analyses were performed using Stata SE .Categorical variables were compared with the χ+ T cell count or plasma HIV-1 RNA level at baseline between the substance use categories. The median year of cohort entry was 2002. Earlier year of cohort entry at CCC was associated with greater likelihood of ever receiving HAART, but lower likelihood of having ≥95% of follow-up time on HAART (P<0.01 for both).The total CCC study cohort was predominantly white and male and median age was 37 years. Of the 1745 persons included, 796 (46%) persons met criteria for history of NIDU, 268 (15%) persons met criteria for history of IDU, and 681 (39%) persons had no drug use history. Comparisons between the three drug use categories demonstrated statistically significant differences in age, race, sex, and follow-up time during the study period. There were differences in likelihood of ever receiving HAART, with persons with no drug use history having the greatest likelihood and persons with a history of IDU having the lowest. The proportion of follow-up time on HAART was also greatest among those with no drug use compared with those having a history of either NIDU or IDU. There was no significant difference in median CD4There were 76 participants with active IDU and 776 with active NIDU recorded during the study period. Active NIDU was present for 644 persons (81%) who were categorized as history of NIDU and for 132 persons (49%) categorized as history of IDU. Among individuals with history of IDU, 69 (26%) had active IDU during the study period.+ T cell count and HIV-1 RNA level at baseline between the drug use categories. The median year of cohort entry was 2001. Earlier year of cohort entry at JHU was associated with greater likelihood of ever receiving HAART (P = 0.04) but not associated with having ≥95% of follow-up time on HAART (P = 0.5).The total JHU study cohort was predominantly black and male and median age was 39 years. Of the 1977 persons included, 731 (37%) persons met criteria for history of IDU. Comparisons between IDU and non-IDU categories demonstrated that individuals with a history of IDU were significantly older, more likely to be black, and less likely to ever receive HAART, and had less follow-up time on HAART during the study period. There was no significant difference in sex, follow-up time during the study period and median CD4+ T cell count <200 cells/mm3 and HIV-1 RNA level >5 log10 copies/mL and longer follow-up time on study were significantly more likely to receive HAART, whereas black race, IDU history and NIDU history each were associated with a lower likelihood of HAART receipt. Among persons exposed to HAART, baseline HIV-1 RNA level >5 log10 copies/mL, black race, and NIDU history were inversely associated with receipt of HAART ≥95% of follow-up time. In Model 2 adjusted for both NIDU and IDU, history of IDU was significantly associated with a decreased likelihood of receipt of HAART ≥95% of follow-up time. Although female sex had a positive association with HAART use ever, women were significantly less likely to receive HAART ≥95% of follow-up time in the CCC cohort.Two logistic regression models were used to assess the effects of age, baseline laboratory values, sex, race, follow-up time, and drug use history on the receipt of HAART in the CCC study cohort. Model 1included only IDU history to be consistent with results of the corresponding model of JHU data shown in . Model 2+ T cell count <200 cells/mm3 and HIV-1 RNA level >5 log10 copies/mL and longer follow-up time on study were significantly more likely to receive HAART, whereas female sex, black race, and IDU history each were associated with a lower likelihood of HAART receipt. Among persons receiving HAART, baseline CD4+ T cell count <200 cells/mm3 and longer follow-up time on study were associated with receipt of HAART ≥95% of total follow-up time. Baseline HIV-1 RNA level >5 log10 copies/mL, black race, and IDU history were inversely associated with receipt of HAART ≥95% of total follow-up time.Receipt of HAART in the JHU study cohort was assessed using logistic regression models that included the effects of age, baseline laboratory values, sex, race, follow-up time, and IDU history. JHU participants with baseline CD4Models including active drug use during the study period, instead of historical drug use, were used to assess the association of activity of drug use with receipt of HAART and proportional time on HAART in the CCC cohort. These analyses showed patterns of associations between active drug use and receipt of HAART that were similar to those observed using historical drug use. In models adjusted for both active NIDU and IDU, IDU during the study period was associated with decreased likelihood of receipt of HAART ever  and ≥95% of total follow-up time , as was NIDU .This study was based on data compiled from the CCC, which serves urban and rural Tennessee, and the urban JHU cohort in Baltimore, Maryland, permitting analysis of IDU and its effects on HAART utilization in two different HIV outpatient populations with up to five years of follow-up. The large sample size provides an opportunity to add to the current literature that reports inconsistent effects of IDU on various HIV outcomes, including HAART use The current study showed that a history of IDU was associated with a decreased likelihood of ever receiving HAART after presentation for care. The lower likelihood of those with IDU history remaining on HAART at JHU may reflect a higher prevalence of active IDU in Baltimore compared to Nashville + T cell count. To our knowledge, this is the first analysis to assess NIDU and HAART utilization in an HIV-infected population. The mechanisms by which NIDU influences HAART utilization and exposure are presumably similar to those for IDU For this analysis, NIDU history was assessed only in the CCC cohort and was also associated with a lower likelihood of ever receiving HAART as well as a decreased likelihood of remaining on HAART ≥95% of the total follow-up time. NIDU affected HAART utilization after adjusting for race, sex, follow-up time, and baseline HIV-1 RNA and CD4An unexpected finding was that sex was associated with ever receiving HAART as well as the probability of remaining on HAART during the study period, but the direction of association differed according to site of care. Females were more likely to receive HAART at CCC, but were less likely to remain on HAART when compared with men. At JHU, women were less likely to receive any HAART, but once on therapy, sex was not associated with likelihood of remaining on HAART. In a Canadian cohort, women were significantly less likely to begin HAART compared with men despite equal access to care One of the strengths of this study, the ability to compare across two geographically distinct urban cohorts, is also a potential weakness. Differences in the clinic populations are evidenced by IDU risk factor rates, baseline demographics such as age, race, and sex, and time in follow-up. Among persons with an IDU risk history, those in the JHU cohort were more likely to be female and of black race than those in the CCC cohort, but the cohorts did not differ significantly with respect to baseline HIV-1 RNA or overall rates of HAART receipt. There also were differences in ascertainment of drug use at CCC compared with JHU. Persons classified solely on the basis of IDU history in both cohorts may have injected heroin or stimulants, such as cocaine and methamphetamine, and may also have used drugs through other routes. Non-injection drug use was characterized only for the CCC, and in this cohort half of those persons categorized with historical IDU had active NIDU during the study period. However, specific categories of NIDU were not distinguished in the CCC analysis. Stimulant users are reported to have the greatest risk of poor adherence compared with both non-drug-users and non-stimulant drug users Methodological differences in data collection and different ascertainment of behavioral information between CCC and JHU may also have affected our findings. Medical chart review and data abstraction were performed for CCC patients, whereas history of IDU was determined for JHU patients on the basis of reported risk factor for HIV acquisition. Documentation of substance use during routine patient care could be affected by provider reliability or individual presumptions. Also, substance-using individuals may minimize the frequency and quantity of drug use depending on the circumstances of self-report , which were not standardized for either cohort.+ T cell count was ≤200 were performed in the CCC cohort to minimize these biases, as all such persons would meet eligibility for HAART initiation. IDU history remained strongly associated with decreased likelihood of receipt of HAART in this model. Adherence to HAART was not assessed for either cohort in this retrospective analysis. Although we determined cumulative HAART exposure, we could not account for unrecorded drug “holidays” or unreported treatment interruptions that were relatively common in practice at times during the study period Bias is inherent in observational data of this nature, and baseline status may have differed among subjects. For example, not all patients were HAART-naïve, some were on HAART, and others may have initiated therapy later in the study period. Analyses limited to persons whose baseline CD4Substance abuse is by nature a dynamic and chronic process, and this variability may explain discordant findings in other studies The present study demonstrated that for the CCC cohort, associations between drug use, receipt of HAART, and proportional time on HAART were not altered significantly whether patients were categorized according to historical drug use or drug use during the study period, which may have occurred before, during or after HAART use. This contrasts with findings from previous studies. For example, a prospective observational study found that historic IDU or any illicit drug history were not associated with decreased patient adherence to HAART, whereas recent drug activity was associated with poorer adherence HIV infection and substance abuse are highly interrelated chronic diseases with consequences that are expanding worldwide. This study demonstrates important negative associations between IDU, NIDU and HAART utilization. Future studies should better characterize patient-level, provider-level, and structural factors that may contribute to utilization of HAART in drug users, and further clarify the effects of different types of drug use on HAART utilization and HIV disease progression.


Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir.Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status.50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir  although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 , week 24 , and week 48  in patients on tenofovir, but differences between groups were not statistically significant.Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs. Current or recent use of abacavir has been associated with an increased risk of developing acute myocardial infarction (MI) in the D:A:D cohort study  and in oIn the SMART study, two inflammatory biomarkers, high sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, were found to be higher among patients who were receiving abacavir than in those using other nucleoside reverse transcriptase inhibitors (NRTIs), suggesting a pro-inflammatory mechanism of the drug . HoweverTo investigate the influence of abacavir on CVD risk, we evaluated longitudinal changes in a number of inflammation , coagulation (plasminogen activator inhibitor-1 [PAI-1]) and endothelial function (intercellular adhesion molecule-1 [sICAM-1] and vascular cell adhesion molecule-1 [sVCAM-1]) biomarkers in viremic patients initiating a regimen including abacavir/lamivudine or tenofovir/emtricitabine, with special attention to the early phases of drug exposure.Eligible patients were all HIV-infected adults  cared for in the outpatient HIV clinic of a university hospital  from December 2006 through March 2008, initiating a regimen including either abacavir/lamivudine or tenofovir/emtricitabine. Candidates for inclusion were ART naïve patients, and patients previously exposed to ART who had discontinued treatment for at least 6 months. Patients who had ever received either abacavir or tenofovir were excluded. For the purpose of this study, only patients who remained on the same ART regimen during follow-up were included in the analyses. HLA-B*5701 screening was not performed, and those patients in whom hypersensitivity reaction to abacavir had been suspected were not included in the study. The study was approved by the Hospital General Universitario de Elche Ethics Committee (CEIC), and an informed consent was obtained from all the patients.Patients were evaluated at baseline and at weeks 4, 12, 24 and 48. At each visit, blood samples were obtained and plasma aliquots stored at -80°C. In January 2009 all frozen samples were defrosted and simultaneously plasma levels of several biomarkers potentially relevant to CVD were measured. More precisely, we determined levels of hsCRP and IL-6 as inflammatory biomarkers; sICAM-1 and sVCAM-1 as endothelial function markers; and PAI-1 as procoagulative marker.Plasma concentrations of IL-6, sVCAM-1, sICAM-1 and PAI-1 were measured using commercially available ELISA kits , and hsCRP with the IMMULITE 2000 Analyzer  as previously described . Intra- 2 and Mann-Whitney tests for categorical and continuous variables, respectively. To assess whether changes in biomarkers levels at weeks 4, 12, 24 and 48 were significantly different from baseline in each treatment group, and whether those changes were significantly different between the two treatment groups, we used linear mixed models including the interaction between treatment group and week of therapy as categorical. Linear mixed models allowed us to accommodate multiple measures per person.Differences in baseline characteristics between the two treatment groups were assessed through the e) as the distribution of the biomarkers was highly skewed. Univariate and multivariate analyses were performed, with adjustment for age, sex, ART status at inclusion (naïve or treatment interruption), viral load, lipodystrophy, Framingham score and hepatitis C virus infection. Considering a 0.05 two-sided significance level, a power of 80% and the sample size of the study, a difference of means ≥ 40% could be detected between groups. All statistical analyses were performed by using Stata software .Changes in biomarker levels were assessed on the natural log scale  initiated abacavir/lamivudine, and 22 (44%) tenofovir/emtricitabine. The third component of the regimen was a non nucleoside reverse transcriptase inhibitor in 68% and 73%, and a protease inhibitor in 32% and 27% patients treated with abacavir/lamivudine and tenofovir/emtricitabine respectively (p = 0.77 for both cases). Of the 50 patients initially selected, 47, 41, 31 and 21 of them remained on the same ART regimen at weeks 4, 12, 24 and 48 of follow-up, respectively, and had plasma samples available for analysis. One patient was of black race (included in the abacavir group) and all the other were caucasians.Thirty two (64%) were ART-naïve patients , and 18 (36%) were patients reinitiating ART after treatment interruption for at least 6 months . Patients initiating tenofovir/emtricitabine were older , and tended to be more frequently male . Other demographic-, HIV- or cardiovascular risk-related baseline characteristics were not different between patients on abacavir/lamivudine or tenofovir/emtricitabine-based regimens, including previous time of exposure to ART, hepatitis C virus coinfection, Framingham risk score, prevalence of classical cardiovascular risk factors, and baseline creatinine clearance by Cockroft-Gault. At week 12, 60.0% and 50.6% patients in abacavir and tenofovir group respectively had a viral load < 50 c/ml, p = 0.77; week 24, 85.0% and 66.7%, p = 0.25; and week 48, 94.7% and 89.9%, p = 0.55. Baseline levels of IL-6 tended to be lower in patients initiating abacavir/lamivudine , week 12 (p < 0.001), week 24 (p < 0.001), and week 48 (p < 0.001), and in the abacavir group at week 24 (p < 0.001) and week 48 (p < 0.001). Decrease was significantly higher with tenofovir at week 12 (p = 0.032). No significant changes both within and between groups were observed in the levels of sICAM-1.The following significant positive correlations were observed between HIV-1 RNA plasma levels and biomarkers at different weeks: IL-6 levels at week 12  and VCAM-1 at week 24 .Our study evaluates exhaustively changes in biomarkers of CVD during the initial weeks of therapy with abacavir/lamivudine or tenofovir/emtricitabine. According to our results, changes in inflammatory, coagulation and endothelial function biomarkers are not different in patients starting an antiretroviral regimen containing abacavir or tenofovir. However, we found a dissimilar effect of ART initiation in the plasmatic CVD risk indicators. While both regimens decreased the endothelial function marker sVCAM-1, the same trend was not observed with the inflammatory biomarkers hsCRP and IL-6, which remained unchanged or tended to increase during the study period. Likewise, the procoagulation biomarker PAI-1 increased soon after starting ART, with significant increases from baseline in patients starting tenofovir/emtricitabine.Our results support an acute effect of the drugs on the inflammatory, coagulation and endothelial function, with significant changes from baseline occurring at an early stage after initiating the drug. Another finding of the study is that initiation of ART does not affect equally to all mechanisms contributing to the atherosclerotic process. The reduction of the biomarkers sVCAM-1 following the administration of both regimens was interpreted as an endothelium targeted effect with anti-atherogenic activity, in agreement with previous observations in naive patients starting ART ,8. ConveStudy limitations are the non-randomized assignment of therapy groups and the small sample size, which might have precluded us from finding significant differences between groups. We do not have an explanation for the trend to different baseline IL-6 levels between arms, which was independent of age and sex. The high proportion of patients with chronic liver disease associated with hepatitis C virus coinfection might have contributed to lessen the differences between treatment groups. However, the investigation benefits from the comprehensive panel of biomarkers measured, and from longitudinal sampling before and at different time points after abacavir initiation, with measurements at the early phases of exposure, and with congruent changes of the markers over time in each treatment group.Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment, in particular during the first weeks after initiating drug exposure, and include anti- and pro-atherosclerotic effects with both drugs. Our results reflect the complexity of phenomena accompanying ART commencement in viremic patients, which might suggest a closer monitoring to high CVD-risk patients during the initial phases of ART.Dr. Sergio Padilla, Dr. Mar Masiá and Dr. Félix Gutiérrez have served as scientific advisors to, or have spoken at events sponsored by GlaxoSmithKline and Gilead Laboratories.SP, MM and FG had primary responsibility for protocol development, data analysis and writing of the manuscript. NG carried out the assays. IJ guided the statistical analysis. CT supervised the laboratory activities. All authors discussed the results and commented on the manuscript and all read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/11/40/prepub


Liver disease is the second cause of death among HIV patients receiving highly active antiretroviral therapy (HAART) in Europe. HIV patients have a high prevalence of chronic HBV (6–10%) and HCV (33%) co-infection, and accelerated progression of viral hepatitis. Furthermore, the long duration of both HIV and HCV diseases in the HAART era increases the risk of hepatocellular carcinoma.trough was found under the minimum level recommended by international guidelines. No grade 3 or 4 toxicities were observed. At month 20 of treatment, new liver lesions with portal vein thrombosis were diagnosed. After 28 months of sorafenib therapy, the patient deceased for severe liver insufficiency.We report the case of a 49 year -old HIV/HCV co-infected male patient who developed hepatocellular carcinoma. The patient underwent a partial hepatectomy, and a few months later was treated with transcatheter arterial chemoembolisation due to hepatocarcinoma recurrence. Two months later, advanced hepatocellular carcinoma was diagnosed and sorafenib therapy was initiated. The patient achieved partial response of the main lesions, complete regression of the smallest lesions and did not experience clinical progression during the 20-month follow-up period. During therapy with sorafenib, the patient was treated with HAART with good viral and immunological responses. We used the therapeutic drug monitoring to assess antiretroviral concentrations during co-administration of sorafenib. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines, suggesting a possible interaction.Sorafenib monotherapy demonstrated a marked delay in HCC disease progression in an HIV/HCV co-infected patient. Fosamprenavir C People infected with HIV have a greater prevalence of chronic HBV 6–10%) and HCV 33%) and accelerated progression of viral hepatitis than the general population 0% and HC. Accordi3% and actrough determination of FPV was 1176 ng/mL, far above the Ctrough levels suggested by international guidelines (>400 ng/mL) [trough was found under the minimum level recommended by international guidelines . Nevertheless, HIV-RNA was still undetectable. At month 20 of treatment, we found an increment of α-fetoprotein up to 200 IU/ml, associated with new hepatic lesions and occurrence of a complete portal vein thrombosis. Sorafenib administration continued after the documented disease progression. In April 2011, after 28 months of sorafenib therapy, the patient deceased for severe liver insufficiency. A summary of CD4 cell count and HIV-RNA values is showed in Table A 49 year-old Italian male with HIV infection (known since 1988), and CDC stage C3 for pulmonary tuberculosis, presented an HCV infection (genotype 4) since 1992. His HBV-DNA and hepatitis B surface antigens were negative. He was on antiretroviral therapy since 1991 with good immune-virological control. In December 2005, a liver biopsy showed a moderate grade of necroinflammatory activity and a moderate intensity of fibrosis . HAART was interrupted in March 2006, and in May 2006, he started antiviral treatment with Peg-interferon 180 mcg/week and ribavirin 1000 mg/day. Sixteen weeks later, antiviral therapy was discontinued for virological failure (> 300.000 HCV-RNA UI/mL). In June 2007, 15 months after HAART interruption, the patient started another antiretroviral therapy with emtricitabine (FTC), tenofovir (TDF), fosemprenavir (FPV) and ritonavir (RTV) (100 mg daily): the CHCC is the fifth most common cancer in the world and the third most common cause of cancer death. The main risk factors for developing HCC are the presence of cirrhosis and co-infection with HBV and HCV .HIV co-infection worsens the course of viral hepatitis causing faster progression of fibrosis and earlier development of cirrhosis. On the other hand, the introduction of HAART has increased longevity. Consequently, the manifestations of end-stage liver disease, particularly HCC, are more frequently reported .in vitro. Two randomized, double-blind, placebo-controlled, multicentre, phase III trials  have proved that monotherapy with oral sorafenib prolonged median overall survival and delayed the median time to progression in patients with advanced HCC [According to current guidelines, treatment of HCC is the same for both patients with and without HIV infection, although the outcome is worse for HIV-positive patients than their HIV-negative counterparts . Until 2nced HCC .Three cases of HIV-positive patients treated with sorafenib have been described in literature: two patients co-infected with HBV ,8 and onIn conclusion, sorafenib may represent a good therapeutic option also for the treatment of HIV-HCV co-infected patients with advanced HCC who are not candidates for surgery or palliative care. However, longitudinal clinical trials are required in order to confirm both efficacy and safety of sorafenib in co-administration with antiretroviral drugs.None; no financial support was received.All authors contributed to the manuscript. PDN was involved in drafting the manuscript and reviewing the literature. AC, MV and RB were responsible for the primary management of the patient. CT and EG helped to draft the manuscript. GV and GME provided the figures and helped to draft the manuscript. EN revised the final manuscript and has given the final approval of the version to be published. All authors have read and approved the final manuscript.


Contemporary data on the immunologic, haematologic and virologic responses and predictors of virologic failure after initiation of free antiretroviral treatment in Cameroon are needed to evaluate the current treatment-monitoring algorithm and to complement efforts to scale-up and improve on the management of HIV infections.Time HIV-1 m2000™ system. Data was analysed using SPSS version 17. The statistical significance level was P < 0.05.This was a cross-sectional study conducted between October 2010 and June 2012. A total of 951 participants aged 18–74 years were recruited from selected approved HIV treatment centres of the Northwest and Southwest regions. This comprised 247 males and 704 females. Demographic, self-reported risk behaviours and socioeconomic data were obtained using a structured questionnaire. Full blood and CD4 + T-cell counts were done using standard automated techniques. Determination of viral load (VL) was done using Abbott RealThe median duration of antiretroviral therapy (ART) was 24 months. The population mean CD4 + T-cell count was 255.3 cells/μL . Overall, 45.9%, 43.8% and 10.2% of the participants had CD4 + T-cell counts of < 200 cells/μL, 200–499 cells/μL and > 500 cells/μL respectively. Anaemia was present in 26.2% of the participants with 62.3%, 25.7% and 12% described as mild, moderate and severe anaemia respectively. Virologic failure occurred in 23.2% of the participants with 12.3% having VL > 10,000 RNA copies/mL. Meanwhile 76.8% of patients attained adequate viral suppression with 40.8% having undetectable viral load. The age group 18–29 years (p = 0.024), co-infection with tuberculosis (p = 0.014), anaemia (p = 0.028) and distance from the treatment centre (p = 0.011) independently predicted virologic failure.The majority of the participants achieved adequate viral suppression after ≥ 6 months of ART. Despite these favourable immuno-haematologic and virologic outcomes, the National AIDS Control Program should step-up efforts to improve on antiretroviral drug distribution, as well as proper assessment and management of anaemia, foster early diagnosis and treatment of tuberculosis and enhance treatment adherence counselling especially in younger patients. Please see Additional file The introduction of free antiretroviral therapy (ART) has substantially improved on the health status of HIV infected patients. Although high levels of adherence have been reported in small-scale HIV programs in Sub-Saharan Africa , more chGenerally, clinical response to ART in resource-limited settings is monitored with CD4 + T cell counts and some hematologic indices ,5. For sHIV prevalence among adults between the ages of 15 and 49 years in Cameroon is 4.3%  shoulderThis was a cross-sectional, hospital-based study involving HIV-infected patients enrolled on high active antiretroviral therapy (HAART), treated between October 2010 and June 2012. Participants were consecutively recruited from the approved HIV treatment Centres of Buea and Limbe Regional hospitals, the management units of the Tiko Central Clinic and Kumba District hospital of the Southwest region; the HIV treatment centre of the Bamenda Regional hospital and the management unit of St. Theresa Catholic Medical Centre of the Northwest region. A nurse assigned to the study obtained demographic and self-reported risk behaviour and socioeconomic data with a standardized questionnaire  and 704 were females . Of 951 these participants, 163 were from the NW and 788 from the SW regions. Over 50% of the study participants were between the ages of 30 and 45 years old. The majority (83.6%) of the study participants had a monthly income of ≤ 50,000 XAF (~ ≤ 100 US dollars), 48.9% had attained more than 7 years of education, while 41.7% reported to be currently married.Most of the participants (88.3%) were receiving treatment at approved treatment centres while 11.7% were treated at the approved management units. The median duration of ART was 24 months [Range: 1–156 months]. Most of the participants (72.9%) were on nevirapine (NVP)-based regimen (17.5% on AZT/3TC/NVP and 55.4% on d4T/3TC/NVP) while 27.1% were on efavirenz (EFV)-based regimen . The prevalence of smoking and alcohol consumption in the study population was 9.1% and 54.3% respectively. Of the alcohol consumers, 48.2% were hazardous drinkers , while 16% of the participants both smoked and drank alcohol. Smoking (p < 0.001) and alcohol consumption (p = 0.003) were significantly higher among males than female participants. A total 10.8% of the study participants were co-infected with tuberculosis  in participants from the SW than NW regions and in the age group > 45 years when compared with those younger (p = 0.018) (Table 3) and thrombocytopenia (PLT < 125 × 103 cells/mm3) in the study participants was 26.2%, 1.6% and 5.9% respectively. Among anaemic patients, 62.3%, 25.7% and 12% had mild, moderate and severe anaemia respectively. Anaemia was significantly higher in patients from the NW region (p = 0.003) when compared to those from SW region. Similarly, females (p < 0.001) and HIV/TB co-infected patients (p < 0.001) were more anaemic when compared to males and HIV-mono-infected patients respectively  counts (p < 0.001). Gender had a significant influence p < 0.02) on mean haemoglobin (Hgb), RBC and platelet (PLT) counts except white blood cell (WBC) count  and detected in 59.2%, while 40.8% of the participants had undetectable viral loads (< 40 RNA copies/mL) at median treatment duration of 24 months (Range: 1–156 months). The difference in mean viral load was insignificant (P > 0.05) between participants from the NW and SW regions , RBC  and WBC  counts correlated significantly with CD4 + T-cell counts. Both haematologic and CD4 + T-cell counts showed a negative correlation with viral load although not statistically significant (p > 0.05). Generally, mean Hgb and CD4 counts improved with ART duration, while mean viral load decreased.In a univariate analysis, socio-demographic Table  and behaSimilarly, duration of ART, co-infection with TB, CD4 + T-cell count and anaemic status were associated with virologic failure. HIV/TB co-infected patients had remarkably higher odds  of experiencing virologic failure than HIV mono-infected patients, while patients on ART for < 12 months had higher odds  than those who have been on ART for 12–36 months and > 36 months. Similarly, anaemic patients  and patients with CD4+ T-cell count < 200 cells/μL  were also prone to failing ART. Nonetheless, there was no significant difference in virologic failure between those on NVP-based and EFV-based regimen , co-infection with TB  and anaemic patients  were again associated with virologic failure. Another model which included all significant variables except HIV/TB co-infection, revealed that the age group 18 – 29 years (p = 0.022), anaemia (p = 0.024) and distance from treatment centre (p = 0.011) with the same adjusted odd ratios as in the previous model were associated with virologic failure.Diminution of CD4 + T-cells and haematological complications are hallmarks of HIV disease progression  associatIn the present study, there was generally, an overall improvement in the means of immunologic and hematologic parameters of study participants with ART duration. The means of all haematologic parameters except that for platelet counts were significantly higher (p < 0.001) in patients who at recruitment were on ART for > 36 months. This increase in immuno-hematologic parameters corresponded with a significant decrease in mean viral loads in participants as ART duration increased  to step-up efforts to improve on ARV distribution, proper assessment and management of anaemia, early diagnosis and treatment of TB and treatment adherence counselling especially in younger patients.ART: Antiretroviral therapy; HAART: Highly active antiretroviral therapy; ARV: Antiretroviral; AZT: Zidovudine; NVP: Nevirapine; EFV: Efavirenz; 3TC: Stavudine; SW: Southwest; NW: Northwest; NACC: National AIDS control committee.The authors declare that they have no competing interests.Conceived and designed the experiments: HDM, TN-A and FC-N. Sample collection and Laboratory analysis: HDM, KAT, MHA and BAN. Analysed the data: HDM and PNA. Contributed reagents/materials: HDM, TN-A, and FC-N. Wrote the paper: HDM, PNA, FC-N and TNA. All authors read and approved the final manuscript.Multilingual abstracts in the six official working languages of the United Nations.Click here for file


Mortality rates within the first year of combination antiretroviral therapy (cART) initiation are several-fold higher in resource-limited countries than in resource-replete settings. However studies in western countries examining virologic, immunologic and clinical responses after cART initiation in indigenous versus non-indigenous populations have shown mixed results. This study aimed to determine whether there is a difference in these outcomes in a United States setting between foreign-born and US-born patients.This retrospective observational cohort study of HIV-1 infected adults in one urban clinic in the United States compared virologic suppression, immune recovery and rates of AIDS defining events (ADEs) within the first year of cART using linear mixed effect models, log rank tests and Cox proportional hazard models. Data were analyzed for 94 foreign-born and 1242 US-born patients.Foreign-born patients were younger (31.7 years versus 38.5 years), more often female (38.3% versus 27.1%), less often injection drug users (3.2% versus 9.5%) or men who have sex with men (19.0% versus 54.5%), and had higher loss to follow-up rates (14.9% versus 6.2%). No significant differences were detected between the groups in suppression of plasma HIV-1 RNA, CD4+ cell recovery or development of ADEs.During the first year on cART, virologic suppression, immune recovery and development of ADEs were comparable between foreign-born and US-born patients in care in a US clinic. Differential rates of loss to follow-up warrant further investigation in the foreign-born population. Patient outcomes in HIV-infected adults initiating combination antiretroviral therapy (cART) have been shown to vary depending on setting. Notably, high rates of early mortality in the months after cART have been reported from several cohorts in resource limited countries, with early mortality rates several fold higher in lower-income countries than in high-income countries.In the United States, foreign-born individuals make up approximately 13% of the population and accounted for approximately 16% of the HIV diagnoses between 2007 to 2010. http://www.r-project.org) was used for all data analyses.We performed a retrospective cohort study among persons in care at the Comprehensive Care Clinic, a Vanderbilt University-affiliated public outpatient HIV clinic in Nashville, Tennessee, USA. The Comprehensive Care Clinic accepts patients regardless of nationality, insurance status or immigration status, with more than 80% of the clinic patients utilizing services funded by the Ryan White Program, a government assistance program for HIV/AIDS care. The study population included all previously ART-naive patients initiating cART between January 1, 1998 and December 31, 2007 whose information had been compiled on a de-identified dataset. To estimate the association between birthplace and viral load suppression and CD4+ cell recovery, a repeated measures analysis was performed on the data using a linear mixed-effects model adjusted for sex, age and baseline CD4+ cell count, creating best fit curves of estimated expected CD4+ cell counts and plasma HIV-1 RNA levels. Time since cART initiation was included in the model using natural splines with three knots. Because the limits of detection for HIV-1 RNA assays changed over time (from <400 copies/ml to <48 copies/ml), we used multiple imputation to assign HIV-1 RNA values of <400 to be from 49 to 399 copies/mL; values <48 were assigned to be 49 copies/mL. The proportion of patients with suppressed viral load was estimated using the distribution of the predicted values of the linear mixed-effects model. Kaplan-Meier estimates were used to calculate hazard rates of death or developing an ADE during the year following cART initiation. A log rank test assessed for differences in rates by birthplace, and Cox proportional hazard models assessed the relationship between time to death or time to ADE and baseline variables. Missing values of baseline predictors were accounted for using single imputation techniques. Country of origin was determined by patient self-report. Patients without documented country of origin (n = 12) were assumed to be from the United States. Foreign-born patients from resource-replete settings (n = 2) were excluded. Patients were deemed lost to follow-up if they had less than one year of follow-up and were not reported as dead within one year of starting cART. Combined antiretroviral therapy was defined as (1) at least two nucleoside reverse-transcriptase inhibitors (NRTIs) in combination with at least one protease inhibitor (PI) and/or non-NRTI (NNRTI); (2) one NRTI and any PI and any NNRTI; or (3) at least 3 NRTIs. R software 2.15.1 . Compared to the dead group, patients lost to follow-up were younger at cART initiation , had higher CD4+ cell counts  and higher hemoglobin levels . These differences, though statistically significant, may or may not be clinically significant.Those who were lost to follow-up were younger (35.2 vs. 38 years) and had slightly lower body mass index and CD4+ cell counts than those who were not lost (data not shown). To further characterize those lost to follow-up, we compared baseline attributes of the lost to follow-up group to patients who were alive and to patients who had died at the end of follow-up to determine which differences were statistically significant. Compared to the alive group, those lost to follow-up had a lower body mass index . There were variables related to the patients’ HIV infection that were not available to the investigators, but may potentially have an effect on outcomes, such as country of HIV acquisition, HIV subtype and duration of infection. In addition, our data are from a single urban US site, so our findings may not be generalizable to other resource-replete settings.Our cohort had a lower proportion of HIV in foreign-born individuals than the national average. This is likely due to the population distribution of foreign-born persons in the United States. Prosser et al noted the variations that exist in the distribution of foreign-born persons and patterns of infection at the state and regional levels. The present study detected no significant differences in virologic suppression, CD4+ cell recovery or development of ADEs in the year after starting cART between foreign-born and US-born HIV-1 infected patients receiving care in one urban US setting. Given the higher loss to follow-up rates among foreign-born patients, a focus on identifying and addressing barriers to retention in care is warranted.


In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered. Combination antiretroviral therapy (cART) has led to declining morbidity and mortality in resource-poor settings , 2, and The Development of Anti Retroviral Therapy in Africa (DART) study compared clinical monitoring only with clinical and laboratory monitoring (CD4 and routine blood tests including biochemistry and full blood count), with switch to second-line therapy on clinical and immunologic criteria. This study demonstrated good clinical outcomes in both arms over the 5-year follow-up period , 7. HereThe NORA Study enrolled 600 previously untreated and asymptomatic Ugandan participants with CD4 counts of <200 cells/µL, randomly assigned to coformulated ZDV/ 3TC and either ABC and NVP placebo (ABC arm), or ABC placebo and NVP (NVP arm). Each drug was taken twice daily. After 24 weeks, participants continued to receive the study drugs open label and were followed as part of DART for a minimum of 4 years. In a separate randomized substudy, participants with a CD4 count ≥300 cells/µL at 48 or 72 weeks after ART initiation were eligible to be randomized to continuous therapy or structured treatment interruption (STI) with repeated 12-week periods on or off therapy ) and 28 (14%) in the NVP arm (from NVP to ABC or TDF).Of the 600 participants randomized in NORA , 32 died before week 96 , 21 were lost to follow-up , and 107 were randomized to structured treatment interruption . Seven participants  switched to a second-line regimen based on lopinavir/ritonavir after week 48 and are excluded from all analyses; all achieved virologic suppression by 96 weeks. The number left for evaluation at week 96 was 236 and 197 in the ABC and NVP arms, respectively .Consistent with previously reported week 48 data , the disP = .82) with viral load >1000 copies/mL at week 48 experienced resuppression by week 96, indicating issues with adherence. Sixty-seven of these 70 patients had drug resistance data at week 48; 10 of 57 (18%) individuals with at least 1 major mutation at week 48 had experienced resuppression by 96 weeks. Resistance patterns present in these 10 individuals were M184V (n = 3), M184V + D67N, M184V + T215Y, M184V + Y181C, M184V + D67N + K70R (n = 3), and Y188C. Among the remaining 10 individuals who had no resistance mutations at week 48, 7 (70%) were resuppressed, suggesting an improvement in adherence after week 48. Two of 3 individuals with no resistance result available at week 48 experienced resuppression by week 96.Nineteen of 70 (27%) of individuals . Thirteen (68%) had only 1 NNRTI mutation, and 5 (26%) participants had 2 NNRTI mutations. The M184V mutation, conferring resistance to 3TC, was highly prevalent . The proportion of participants with ≥3 thymidine analogue mutations (TAMs) at week 96 was similar between the ABC group (49%) and the NVP group (42%) (P = .79). In the former group, ABC-specific mutations L74V and K65R were each seen in 1 individual. The pan–nucleoside resistance mutation Q151M was not observed in any individual.Of 91 participants with viral load ≥1000 copies/mL) at week 96, 87 (96%) had a genotype available. Five  participants with baseline resistance were excluded, leaving 82  patients for analysis. The frequencies of mutations for both the intention-to-treat and on-treatment populations are given in We present 2-year virologic data from the DART-NORA study, highlighting the very good suppression rates achieved using ZDV/3TC and NVP. Viral failure as defined by WHO  was almoWe noted that most individuals treated with NVP who developed NNRTI resistance had a single mutation only, consistent with previous reports examining viral failure with both efavirenz- and NVP-containing regimens –17. ThisMost importantly, we found that one-quarter of individuals with viral failure (>1000 copies/mL) at week 48 experienced resuppression at 96 weeks even though real-time viral load testing was not undertaken. This was most likely due to an improvement in adherence. It is notable that resuppression occurred in the presence of major resistance mutation(s) at week 48 and no change in therapy, suggesting that strong antiviral activity is possible despite reduced viral susceptibility, although the role of adherence cannot be ignored. Drug substitutions due to poor tolerability/side effects did not account for the observed changes in viral load. In South Africa, where real-time viral monitoring has taken place, substantial rates of resuppression without modification of ART have also been reported, even in patients with NNRTI resistance . Where VSupplementary materials are available at Clinical Infectious Diseases online . Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.


The aim of this study was to investigate the impact of a tenofovir disoproxil fumarate (TDF) plus ritonavir-boosted protease inhibitor (PI/r) regimen on renal function in Chinese HIV-infected patients.Seventy-five HIV-1 infected patients failing first-line antiretroviral therapy (ART) comprised the TDF+PI/r group. Seventy-five HIV-1 infected patients matched for gender, age, and renal function made up the control. All subjects completed follow-up visits over 48 weeks. CD4 cell count, plasma HIV-1 viral load, and urine protein level were assessed at the trial start  and at week 48. The serum creatinine and estimated glomerular filtration rate (eGFR) were monitored at each follow-up point. Change in eGFR from baseline to week 48 was also compared.P<0.001) and a lower rate of eGFR  at the end of week 48. Patients treated with TDF+PI/r showed greater decline in eGFR than control . Compared to baseline renal function of the control group, the TDF+PI/r group exhibited a greater median decline in eGFR at the end of week 48 (P<0.001).Compared to control, the TDF+PI/r group exhibited higher levels of serum creatinine (79 vs. 69.7 μmol/L, We found that a TDF+PI/r based ART regimen resulted in greater renal function decline over 48 weeks. Therefore, renal function should be monitored especially when TDF is used in combination with PI/r.NCT00872417ClinicalTrials.gov identifier:  Combined antiretroviral therapy (cART) has reduced the mortality and morbidity associated with human immunodeficiency virus type 1 (HIV-1) infection and the risk of HIV-infected patients’ progression to Acquired Immune Deficiency Syndrome (AIDS). Side effects have been reported in the past decades. Complications related to long-standing HIV infection and treatment, such as the nephrotoxic effects, have become the focus of researchers. cART can itself cause renal toxic effects directly by inducing acute interstitial nephritis, crystal nephropathy, and renal tubular disorders , is wellTDF is eliminated largely by glomerular filtration, and 20%-30% by active renal proximal tubular secretion . PreviouLittle is known about renal safety of TDF in Asian patients on tenofovir. TDF has been provided at no cost by the Chinese government as a second-line therapy to HIV-infected individuals who failed first-line treatment since mid 2009. Moreover, the government has classified TDF as a first-line therapeutic since 2012. It is thus urgently necessary to determine TDF effects on renal function. In this study, we report the outcome of a 48-week prospective study on renal safety data of TDF plus ritonavir-boosted protease inhibitor (PI/r) based cART regimens in Chinese adult HIV-infected patients.2, and (4) anticipated poor adherence. Seventy-five HIV-1 infected cART-naïve patients matched for gender, age, serum creatinine and eGFR were selected from a multicenter cohort study population and made up the control group. Control patients were given a cART regimen of D4T/AZT+NVP+3TC. All subjects complied to follow-up visits over 48 weeks from 2008 to 2010. To further investigate the influence of TDF+PI/r-based cART regimens on renal function between individuals with normal and abnormal renal function, the TDF+PI/r group was divided into a normal renal function (eGFR≥90 ml/min/1.73m2) sector and an abnormal one (90>eGFR≥50 ml/min/1.73m2) based on eGFR baseline. To note, the control group subjects were not on an ART regimen, but TDF+PI/r patients were receiving a first line ART regimen before the start, switching to a second line ART regimen (TDF + 3TC+ LPV/r) at the study’s beginning. Informed consent was obtained from each participant. Ethics approval was obtained from the Institutional Review Board of Peking Union Medical College Hospital (PUMCH).This was a prospective, observational study conducted at eight research centers in China. Patients were recruited from several different regions of the country including Beijing, Shanghai, Guangzhou, Shenzhen, Fuzhou, Henan, and Yunnan provinces between November 2008 and January 2010. Seventy-five HIV-1 infected patients with first-line cART regimen treatment failure were enrolled in the TDF+ ritonavir-boosted protease inhibitor (PI/r) group. Patients all received second-line cart: TDF + ritonavir-boosted lopinavir (LPV/r) + Lamivudine (3TC). Inclusion criteria of this group included: (1) 18–65 years of age , (2) first-line cART failure defined as receiving first-line cART  + 3TC + Nevirapine (NVP) / Efavirenz (EFV), twenty patients treated with Stavudine (D4T) + 3TC + NVP / EFV, fifteen patients treated with AZT + Didanosine (DDI) + NVP / EFV and five patients treated with D4T + DDI + NVP / EFV.) for one year with plasma HIV-1 viral load (VL) more than 1000 copies per milliliter (cps/ml), and (3) available estimated glomerular filtration rate (eGFR). The main exclusion criteria were (1) patients who had received initial cART regimes containing TDF and/or protease inhibitors (PIs) (2) serum creatinine >1.5 times the upper limit of normal, (3) eGFR< 50ml/min/1.73mThe following clinical and laboratory data were collected and recorded on case report forms: age, gender, race, duration of HIV seropositive, weight, height, hypertension, diabetes mellitus, smoking, CD4+ cell count, plasma HIV-1 viral load, urine protein level, serum creatinine, and eGFR. Hypertension was defined as either blood pressure greater than 140/90mm Hg on at least two of any three preliminary clinic visits, or the use of an antihypertensive medication. Diabetes mellitus was defined by physician diagnosis or by patient use of an antidiabetic agent. CD4 cell count, plasma HIV-1 viral load, and urine protein level were monitored at start and week 48. Serum creatinine and eGFR were monitored at start and at weeks 0, 4, 8, 12, 24, 36, and 48. Change in eGFR from week 0 to 48 for TDF+PI/r and control groups was compared. Urine protein level and serum creatinine were administered by PUMCH clinical laboratory departments. The eGFR was calculated using the four-variable Modification of Diet in Renal Disease (MDRD) . Urine pt test or Mann–Whitney test appropriately. Categorical variables were assessed with the Chi-square test. Differences in changes in serum creatninine and eGFR at 48 weeks were assessed using the Wilcoxon rank sum test to compare median values of continuous data. Absolute differences for each group in serum creatinine and eGFR were respectively analyzed during the follow-up using repeated measures of variance. The Wilcoxon signed rank test was used to assess trends in serum creatinine or eGFR during the follow-up. For all tests, a P-value less than 0.05 was considered statistically significant. Statistical analysis was conducted via SPSS version 16.0 .All analyses were performed on the intent-to-treat (ITT) population. Missing values were imputed for the analysis with the last-observation-carried-forward method. Continuous variables were assessed with the Student’s P<0.001).A summary of patient characteristics in both TDF+PI/r and control groups are summarized in Tables P<0.001) and a significantly lower rate of eGFR . BMI was similar for TDF+PI/r and control groups . No difference was noted in CD4 cell count  or HIV-1 RNA viral load . Importantly, however, median eGFR did change from start to 48 weeks for TDF+PI/r patients vs. control . Patients treated with TDF+PI/r showed declining eGFR levels.Using intent-to-treat (ITT) analysis at the end of week 48, TDF+PI/r patients exhibited higher levels of serum creatinine . For the TDF+PI/r group, the median [IQR] serum creatinine concentration was 71.0 [65.0-81.0] μmol/L at baseline, and varied between 78.0 and 81.0 μmol/L between 4 and 48 weeks. We found that compared with baseline, the median values of serum creatinine for the 4-week point were significantly higher in TDF+PI/r group  (P=0.002). However, the median values of serum creatinine between the 4-week point and the 48-week point were no significant differences in TDF+PI/r group  (P=0.719). So it demonstrated that the values of serum creatinine increased significantly initially (0–4 weeks), and then (5-48weeks) maintained at the stable level in TDF+PI/r group.The changes in serum creatinine concentrations during the 48 week follow-up period are shown in Figure 2 with no significant differences at each follow-up point. For the TDF+PI/r group, median [IQR] starting eGFR was 101.6[85.6-117.2] ml/min/1.73m2 and varied between 88.8 and 94.2 ml/min/1.73m2 between 4 and 48 weeks. Compared with baseline, the median eGFR for the 4-week point were significantly lower in TDF+PI/r group  (P=0.001). However, the median values of eGFR between the 4-week point and the 48-week point were no significant differences in TDF+PI/r group  (P=0.725). So it showed that the median values of eGFR decreased significantly initially (0–4 weeks), and within 5–48 weeks, median eGFR remained relatively stable in participants treated with TDF + LPV/r + 3TC. We also calculated creatinine clearance (CrCl) using the Cockcroft–Gault equation, and saw a similar trend, as eGFR changes throughout the 48 weeks between the two groups (data not shown).Changes in eGFR during the 48 week follow-up are shown in Figure 2) or abnormal (90>eGFR≥50 ml/min/1.73m2) groups: 52 and 23 patients were respectively divided into these groups. Significant differences in eGFR levels between these groups at baseline  and at week 48  were observed. Changes in median eGFR during 48 weeks of TDF+PI/r-based cART treatment between the two groups are shown in Figure P<0.001), but renal function always fluctuated within normal range. For eGFR abnormal patients, no significant differences in median eGFR were found at 0, 4, 8, 12, 24, 36, and 48 weeks. For these patients, magnitude of eGFR decline was mild, and severe renal dysfunction was not observed during follow-up. Baseline eGFR normal patients exhibited greater decline in eGFR than eGFR abnormal patients at 4, 8, 12, 24, 36, and 48 weeks, but renal function still fluctuated within the normal range. For two (8.7%) patients, eGFR decreased to less than 50ml/min/1.73m2, but severe renal dysfunction was not detected during the 48 week follow-up. After 48 weeks, no significant difference in proteinuria incidence between the two groups  was apparent.To further analyze the impact of TDF+PI/r-based cART regimens on renal function between renal function normal and abnormal patients, 75 TDF+PI/r patients were stratified by kidney function into normal  for over a year. To our knowledge, first-line therapies mentioned previously were not known to be associated with renal damage. However, using cART and suppressing HIV RNA may improve kidney function , reduce 2 . Moreover, 30% lost >10 mL/min/1.73m2 during the 2-year follow-up period. Goicoechea et al. [2/year). Consistent with observations in the Western population, median changes of eGFR were −8.8 ml/min/1.73m2 in TDF+PI/r and 6.4 ml/min/1.73m2 in control. Patients treated with TDF and PI/r showed greater decline in renal function over 48 weeks compared to non-TDF-containing regimens. Gallant JE et al. also illustrated that patients taking TDF and a PI/r exhibited a greater median decline in eGFR than those taking TDF and a non-NRTI at 6 months, with trends at 12 and 24 months [2 and less advanced HIV disease were included in our study. Moreover, the comparator group contained both TDF- and other PI+TDF-treated patients. This may have influenced the decreased renal function observed in their study, reducing the window to discern an effect between treatment groups.Nancy Crum-Cianflone et al.  evaluatea et al.  compared4 months . A smallFor tenofovir-induced nephrotoxic effects, approximately 70% are observed with concomitant use of low-dose ritonavir . Due to For our analyses of kidney function over time among patients using TDF+LPV/r+3TC, the impact of TDF+ PI/r was apparent within the first 4 weeks and stabilized to 48 weeks. Consistent with an observation from a Development of Antiretroviral Therapy (DART) trial in a large cohort of HIV-infected African adults from Uganda and Zimbabwe, changes in eGFR were also observed predominantly during early exposure to TDF cART regimens, with kidney function stabilization after ~4 weeks . ContrasIn our study, patients were Chinese, and 90% were of the Han race. All patients in TDF+PI/r group had never taken TDF and/or PIs-containing cART regimens, nor did they use nephrotoxic drugs prior to the trial. Thus, a plausible explanation for this discrepancy resides in the longer follow-up of the EuroSIDA cohort, genetics, difference in treatment history, and inclusion patients who may have had pre-existing risk factors for CKD, subsequently increasing the risk of TDF-related CKD.2). We expect an observable significant decline in patients’ renal function whose baseline is 90>eGFR≥50 ml/min/1.73m2. We were thus surprised to detect no significant differences in median eGFR at 0, 4, 8, 12, 24, 36 and 48 weeks for patients with baseline 90>eGFR≥50 ml/min/1.73m2. Perhaps patients with this basal eGFR remain insensitive to nephrotoxic side effects, but may be hypersensitive to renal dysfuntion. Our cutoff for group sorting may be too broad to detect eGFR changes, since TDF impact on GFR is normally small. Studies confirming our hypotheses require further elucidation.The impact of a TDF+PI/r-based cART regimen on renal function was analyzed in patients stratified by baseline eGFR. Baseline eGFR was divided into two categories  and serum phosphate measured no less frequently than every 6 months, and also should be analyzed for proteinuria and glycosuria [Early detection and diagnosis of renal dysfunction are essential for preventing or at least slowing kidney function decline to ultimately improve outcome in HIV-infected patients. Individuals with underlying impaired kidney function and patients whose kidney damage was drug-induced would likely benefit from vigilant renal follow-up. Particularly, patients receiving tenofovir may benefit from frequent assessments of kidney function, serum phosphate levels, and urinalyses to monitor for early signs of nephrotoxicity ,30. The ycosuria . EvidencOur study reports that incidences of proteinuria were not significant for both groups at weeks 0 or 48. Tenofovir is thought to primarily affect proximal renal tubular function , yet glo2 were excluded from our study. The influence of TDF based cART regimens on renal function in HIV-1 with compromised renal function remains poorly understood. Patients with renal dysfunction treated with TDF cART regimens should be frequently monitored by nephrologists. Finally, our last time point was 48 weeks. Further follow-up in a larger cohort would be required to more accurately determine long-term TDF-related nephrotoxicity. In view of these limitations, a prospective long-term multicenter clinical trial is being considered to investigate the potential impact of TDF on renal function in Chinese HIV-infected individuals. Future trials may include older patients and patients with moderate to severe renal dysfunction.Our study does have limitations. First, patients in the TDF+ PI/r group were receiving first-line cart prior to the study, while control patients were naïve. Second, only 3 patients older than 60 were enrolled. This study was thus not designed to decipher an effect of TDF on renal function of older patients, and the safety of TDF on older patients should be assessed in the future. Third, patients whose serum creatinine > 1.5 times the upper limit of laboratory normal and/or eGFR< 50ml/min/1.73m2, TDF+PI/r based cART regimens could influence non-progressive eGFR decreases, but the impact of TDF+PI/r based cART regimens on eGFR in patients with abnormal renal function seemed to be relatively minor. Additionally, renal function rapidly decreased during the first four weeks. Our results suggest that renal function should be monitored over the first four weeks of follow-up, especially when TDF is combined with PI/r.In conclusion, TDF+PI/r based cART regimens were associated with a higher level of serum creatinine and a greater decline in renal function over 48 weeks compared to control. For patients with baseline eGFR ≥90 ml/min/1.73mThe authors declared that they have no competing interest.YC assisted with the study design, performed the data statistical analyses, and wrote this manuscript. YH recruited patients and performed HIV-1 viral load tests. JX determined CD4+T cell count. QC and YL assisted in drafting the manuscript. LZ performed the renal function assay. YL and XS collected clinical data. TZ performed the HIV-1 viral load test. TL designed and supervised this study. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/301/prepub