These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART) of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure.Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process.3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine), or a ritonavir-boosted protease inhibitor (atazanavir or darunavir). Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression with or without identified opportunistic infection, and person who injects drugs are addressed. Options for optimization of ART once virologic suppression is achieved are discussed. Evaluation and management of virologic failure are described, the aim of any intervention in such situation being to reduce plasma viral load to <50 copies/ml.ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mmThese guidelines recommend that any HIV-positive individual should be treated with ART. This recommendation was issued both for the patient’s own sake and for promoting treatment as prevention. Guidelines presented in this article are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the national health authorities in September 2013 .The ENCORE 1 trial recently showed a similar virological efficacy for efavirenz administered at the dosage of 400 or 600 mg/day (in combination with tenofovir DF/emtricitabine)  metabolized by cytochrome CYP2D6 and certain benzodiazepines metabolized by cytochrome CYP3A4) [The risk of pharmacological interactions between antiretrovirals and injectable or substitution drugs  should be taken into account when choosing antiretrovirals. Enzyme inducers  generate the risk of under-dosing of morphine-like drugs, the dose of which, if used, should be increased. Conversely, enzyme inhibitors  generate the risk of over-dosing of certain intoxicants (notably ecstasy and  CYP3A4) .When a sustained virologic suppression has been achieved on ART (VL under the limit of quantification for more than 6 months), treatment optimization can be proposed. The aim is to improve quality of life, promote long-term adherence, and prevent virologic failure.Most current antiretroviral combinations include two NRTIs and a third drug. There is greater toxicity, notably mitochondrial , with first-generation NRTIs, which should be replaced by more recent NRTIs, available as once daily single tablet fixed-dose combinations (tenofovir DF/emtricitabine or abacavir/lamivudine). Stavudine should no longer be used. Didanosine and zidovudine should also be replaced.When the third drug is a PI/r, it can be changed in the case of intolerance, or in prevention of long-term toxicity.Darunavir/r and atazanavir/r are easier to use than older PIs/r  and have a better gastrointestinal safety. In the absence of previous failure of a treatment including a PI/r, it is easy to replace an old PI/r by darunavir/r or atazanavir/r.The use of atazanavir without ritonavir can also be considered, at the dose of 400 mg/day. The aim is to improve the safety of the treatment by withdrawing ritonavir . Virological efficacy has been maintained up to 144 weeks  and is aSeveral randomized trials have shown the efficacy of such a treatment strategy, with efavirenz or nevirapine. The replacement of PI/r by rilpivirine was evaluated in a randomized, open, non-inferiority trial in 476 patients with virologic suppression for over six months on a first- or second-line triple-drug therapy combining two NRTIs and a PI/r. Patients in the intervention arm received the fixed-dose combination rilpivirine/tenofovir DF/emtricitabine once daily; patients in the control arm continued the treatment they were taking at the time of enrolment. Non-inferiority was demonstrated. The rate of virologic failure was lower in the rilpivirine/tenofovir DF/emtricitabine arm (0.9%) than in the control arm. These strategies have the advantage of simplifying treatment, notably in terms of number of tablets, and of improving safety . It is essential to check that the NRTI to be combined with NNRTIs is fully active . The initiation of nevirapine in a treatment switch in patients with virologic suppression does not call for the same precautions concerning CD4 count as on the introduction of a first treatment .Replacement of the PI/r by raltegravir also simplifies the on-going treatment regimen and improves safety (lipid profile), but it requires two doses a day and, as for NNRTIs, necessitates a check that there are no resistance mutations to the NRTIs taken by the patient, because of the risk of virologic rebound when the combined antiretrovirals are not fully active ,54.Maintenance strategies using PI/r monotherapy have been investigated in numerous randomized or cohort studies, mainly for lopinavir/r and darunavir/r. A meta-analysis of 10 randomized trials  including 1189 patients showed that PI/r monotherapy was less virologically effective than maintenance of the on-going triple-drug therapy . HoweverA first trial with atazanavir/r in maintenance monotherapy recorded five virologic failures after the inclusion of 15 patients, leading to discontinuation of the study ,57. An o6 PBMC) and good adherence to treatment.These studies have identified the factors associated with maintained virologic suppression on PI/r monotherapy: use of lopinavir/r or darunavir/r, absence of previous virologic failure on protease inhibitor, prolonged virologic suppression on triple-drug therapy, low HIV-DNA +darunavir/r (800/100 mg once a day) reveals an interesting pharmacokinetic profile, notably at the maraviroc dosage of 300 mg/day, which is similar to that of maraviroc 300 mg twice a day combined with tenofovir/emtricitabine . No recoThe ANRS ROCnRAL trial  has evaluated the efficacy of the combination raltegravir (2×400 mg/day)+maraviroc (2×300 mg/day) in 44 patients with a VL <50 copies/mL (R5-tropic virus) on triple-drug therapy including two NRTIs, and presenting lipodystrophy. The study was interrupted after the occurrence of five virologic failures, with selection of resistance mutations to integrase in three cases, a change in tropism (from R5 to X4) in one case and two serious adverse drug reactions. Consequently, this combination cannot be recommended.The success of switching to the combinations of raltegravir+nevirapine and raltegravir+etravirine has only been evaluated in a small number of patients in non-comparative studies. No recommendations can be made about such combinations until results of randomized clinical trials are available.The aim of ART in all situations  should be to reduce VL to <50 copies/mL and keep it there.Non-response to treatment is defined as a less than 2-log reduction in VL one month after the introduction of the first session of treatment, or a less than 1-log reduction one month after the introduction of a treatment of suboptimal efficacy prescribed when there is virologic failure with multiple resistance.Initial failure is defined as the persistence of a detectable VL . The higher the VL at treatment initiation, the longer it takes to reduce it to an undetectable level (<50 copies/mL).Virologic rebound is defined as an increase in VL to >50 copies/mL after a period of virologic suppression, confirmed for two consecutive samples, and should be distinguished from simple blips . This blip usually corresponds to an isolated replication accident, often following a period of less strict adherence or an intercurrent infectious episode. Blips have no consequences in terms of the risk of later virologic failure or CD4 count [D4 count –62, and low but repeatedly quantifiable VL (>20 copies/mL). The consequences and the management of such situations are described below in “Management of low viral replication (VL <200 copies/mL).”Depending on the detection threshold of the technique used to determine VL, some patients have a confirm the virologic failure: any detectable VL should be checked quickly; a second detectable measurement confirms virologic failure and distinguishes it from a virologic blip,measure the CD4 count, check its nadir and evaluate the patient’s clinical condition,evaluate adherence, notably looking for factors associated with poorer observance: adverse drug reactions, psychological difficulties, neurocognitive disorders, addictions and social vulnerability…perform a pharmacological evaluation: suitability of the doses and observance of timing of doses, notably when taken at mealtimes; testing for drug interactions; assays of residual plasma antiretroviral concentrations.collect the patient’s treatment history and analyze previous virologic failures and tolerability of previous drug regimens. In the case of a history of virologic failure on a treatment, including an NNRTI, an integrase inhibitor or lamivudine/emtricitabine, there may be resistance to these antiretrovirals, even if it has not been evidenced by a genotypic test.www.hivfrenchresistance.org). If VL is <1000 copies/mL, problems with HIV-RNA amplification are likely and a larger volume of plasma can be concentrated to increase test sensitivity. In the case of failed amplification of plasma HIV-RNA, after consulting with a virologist, a genotypic resistance test may be performed on HIV-DNA in peripheral blood cells.review resistance by collecting the results of previous genotypic resistance tests and by performing yet another test on plasma HIV RNA, always including analysis of the genes of reverse transcriptase and protease. Plus, depending on the case, analyze the genes of the integrase or of the viral envelope in the gp41 region in cases of prior exposure to integrase inhibitors or to fusion inhibitors, respectively. A tropism test can also be done to look for CXCR4-tropic virus, which would contraindicate the use of CCR5 inhibitors. Genotypic resistance tests are ideally done during the treatment that has resulted in virologic failure and are interpreted according to the latest recommendations of the ANRS group AC11  are not as clearly established as when replication leads to a VL >200 copies/mL. The same is true for replication below the lowest detection thresholds of current routinely used techniques (i.e. 20 copies/mL). If the patient receives a treatment including antiretrovirals with a low genetic barrier , the risk of selecting additional resistance mutations increases with the level of viral replication and its duration ,64. ThisThe priority is to eliminate known causes of virologic failure. If there are adherence problems not related to adverse drug reactions, a change of treatment is not generally the most appropriate response. Simplification of the treatment  may improve adherence. If viral replication persists, particularly if VL increases and approaches 200 copies/mL, and if the patient is receiving NNRTIs or integrase inhibitors, a change of treatment should be considered, so as to prevent the selection of new mutations. In this situation, a resistance genotype test is most often not possible for a VL <200 copies/mL, because of failure of amplification (55% failure of amplification when the VL is between 51 and 500 copies/mL). The preferred choice will be a treatment including a PI/r.Persistence of viral replication (VL >200 copies/mL) under antiretroviral selective pressure creates the risk of selection and accumulation of resistance mutations, plus immunological deterioration, which may lead to clinical progression and increased HIV transmission risk.Rapid intervention is necessary whatever the CD4 count. The priority is to eliminate identified causes of virologic failure, such as a problem of adherence or a pharmacological cause. If the genotypic resistance test reveals new resistance mutations, rapid intervention is needed to avoid their accumulation, in particular with NNRTIs or integrase inhibitors, because of the risk of decreased efficacy of second-generation drugs of these classes . The choWith currently available antiretrovirals, the aim of controlling viral replication (VL <50 copies/mL) can be achieved in most cases, including in patients with a long history of ART and the presence of more than one class of resistance mutations. Whenever possible, combinations evaluated in clinical trials should be preferred.The optimal situation is when a treatment regimen containing three active drugs can be devised, based on treatment history and all the genotype data.not used previously;already used but for which the current resistance genotype and all the genotype data suggest it is active.The new treatment will preferably combine an active PI/r , with two other active antiretrovirals chosen from among:etravirine ;raltegravir;dolutegravir 50 mg twice a day for patients with a virus presenting resistance mutations to raltegravir . The SAImaraviroc, provided a tropism test done at the time of failure does not reveal a virus using the CXCR4 co-receptorenfuvirtide (though its injectable form limits prolonged use)one or more NRTIs. In the case of multiple resistance to NRTIs , there may be residual activity of abacavir and tenofovir. All clinical trials performed with new antiretrovirals during the period 2002–2009 included optimized treatment with NRTIs, suggesting their possible contribution to the observed efficacy. In view of their good safety and ease of use, the maintenance of lamivudine or emtricitabine in the presence of the mutation M184V can be envisaged to maintain lower viral replication capacity.In the TRIO trial, the combination of darunavir/r (600/100 mg twice a day), etravirine and raltegravir, with or without NRTIs and enfuvirtide, reduced VL to <50 copies/mL in 86% of patients by the 48th week [An antiretroviral can be considered active if it belongs to a class:8th week .When VL is <4 log copies/mL, a partial change including at least two active drugs, one of which is a PI/r, can be sufficient ,71.Multiple resistance is less and less frequent in recent years in France where <1% of patients have viruses resistant to all NRTIs and protease inhibitors . In the If genotypic resistance testing reveals resistance to all available drugs, the on-going treatment should not be changed pending the possibility of offering active multidrug therapy. It is sometimes useful to increase the doses of PIs/r, while monitoring plasma concentrations, to obtain a concentration that is effective against multidrug-resistant strains. Cohort studies have shown that the maintenance of a stable CD4 count despite virologic failure is accompanied by a lower risk of clinical progression. The use of foscarnet can be discussed case-by-case in the absence of another therapeutic possibility, to reduce the VL before introducing an ART that is not fully effective .AIII).In these situations of multiple failure, therapeutic decisions should be taken at a multidisciplinary meeting. The opinion of a team experienced in the management of these patients is indispensable in situations where the therapeutic options seem limited .® by three generic tablets of each of its components in virologically suppressed patients was followed by maintained virologic suppression . However, an increased daily number of tablets may not be well accepted by, and even can be deleterious to some patients.These guidelines are likely to evolve rapidly as generic antiretrovirals, which will be markedly less expensive than reference drugs, gradually become available ,74. This3, which is in line with DHHS guidelines [These guidelines recommend that any individual living with HIV should be treated with ART, irrespective of his/her CD4 cell counts and/or HIV plasma VL, including when CD4 cell count is above 500/mmidelines  but broa


Many studies reported in HIV-positive patients 50% of hepatitis B vaccine response with a duration of protection between 24 and 36 months. The aim of our study is to determine the long term protection in our HIV patients who responded to a standard immunization schedule.Our database NADIS allows us to collect information from March 1986 to October 2013 Patients were included gradually after 3 Engerix B 20 hepatitis B vaccines at day 1, one month and 6 months later, conferring a rate of HBs ab > 10 IU /L. Then we observed the duration of protection from the initial response.Among 403 HIV patients who responded to HBV, 298 were men (74%) vs 105 women (26%). The median age was 36 years. We observed a progressive decline in HBs ab titer until <10 IU/ L. At 24 months 74.7% (n=223) men remained protected vs 79.2% (n=83) women. At 60 months. 33.1% (n=99) men lost their HB protection vs 27.7% (n=29) women .At 84 months and over 120 months, 34.7% (n=103) and 39.1% (n=117) men lost their HB protection vs 35.8% (n=38) and 38.2% women (n=40).Long term HBV protection was observed in the majority of our HIV patients. One third had lost their HBs ab after 2 years, and require HB boost injections. We are thinking of using an adjuvanted HB vaccine as a booster to provide a sustained protection. We will also study factors associated with the loss of HBV protection.


Current international and national treatment guidelines such as EACS, BHIVA, DHHS or IAS update regularly recommendations on the choice of initial combination antiretroviral treatment (cART) regimens. Preferred cART regimens include a backbone with two nucleoside (nucleotide) reverse transcriptase inhibitors combined either with one non-nucleoside reverse transcriptase inhibitor or one ritonavir boosted protease inhibitor or more recently one integrase inhibitor. Response rates according to viral load measurements increased in recent years, in particular due to better tolerability. The choice of initial therapy is flexible and influenced by several factors such as height of viral load, genotypic resistance testing, CD4 cell count, co-morbidities, interactions, potential adverse events,  pregnancy, convenience, adherence, costs as well as physician's and patient's preferences. Diverse highly potent initial cART regimens exist. Following the many possibilities, the choice of a regimen is based on a mixture of evidence-informed data and individualized concepts, some of the latter only partly supported by strong evidence. For example, different perceptions and personal experiences exist about boosted protease inhibitors compared to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors and vice versa which may influence the initial choice. This lecture will discuss choices of initial cART in view of international guidelines and the evidence for individualization of initial HIV therapy.


The efficacy of protease inhibitor monotherapy has been analyzed with different endpoints: initial HIV-1 RNA rebound, long-term HIV-1 RNA suppression after re-intensification, treatment-emergent drug resistance, neurocognitive testing and HIV-1 RNA in the cerebrospinal fluid (CSF).A PUBMED search identified nine randomised trials of PI monotherapy versus triple therapy in patients with HIV RNA<50 copies/mL at baseline. Results from the recently completed PROTEA trial were also included. The percentage of patients with HIV RNA suppression <50 copies/mL was analyzed using switch equals failure and intensification included endpoints (ITT). The number of patients with new drug resistance mutations, HIV RNA in the CSF or change in neurocognitive function was analyzed by treatment arm.Four trials evaluated darunavir/r monotherapy , five evaluated lopinavir/r monotherapy  and one evaluated both . HIV-1 RNA suppression rates tended to be lower on PI monotherapy than triple therapy in “switch equals failure” analysis (76% vs 82%), but not when the outcome of intensification was included (87% vs 85%). There were small numbers of patients taking PI monotherapy with detectable HIV-1 RNA in the CSF, in three trials: PROTEA (n=2), MONOI (n=2) and MOST (n=5), but only two cases of CSF viral escape (MONOI). In two trials, there was no difference in neurocognitive test results between PI monotherapy and triple therapy, based on z-scores from five domains ; similar results were observed in the MRC PIVOT trial. The risk of treatment emergent NRTI or PI resistance  was 11/9In 10 randomised trials of 1964 patients with HIV-1 RNA suppression at baseline, PI monotherapy showed a higher risk of HIV RNA elevations, and small numbers with HIV RNA detectable in CSF and concomitantly in the plasma. However there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints were not different between the arms and HIV-1 RNA suppression rates after intensification were similar between PI monotherapy and triple therapy.


Antiretroviral (ARV) treatment available in low-middle income countries differs as suggested in international HIV-treatment guidelines. Thus, we compared ARV regimens introduced as a first-line therapy, time of initiation, frequency of making combination antiretroviral therapy (cART) switches, frequency of viral and immunological monitoring and treatment outcome in south east European (SEE) country ) and west European country ).ARV naïve patients starting cART from 2003 to 2012 were included. Comparisons of the two cohorts were made using a chi-square test or Fisher's exact test for categorical variables and a Mann-Witney U test for continuous variables. Kaplan Meier survival curves were compared using the log rank test.3 vs 238 cells/mm3). The total  CD4+ T cell count measurements in the first year of cART was 2  at the HCB, while it was statistically significant higher at the RFH 5 , respectively (p<0.0001). At the RFH, it appeared that the cART switching is due to patient's preference or toxicity (46%), while the lack of supply and toxicity (37%) were the most important reasons for treatment change in HCB, within the same period of time (p<0.05). Mortality rates were higher at the HCB versus RFH (p<0.0001). After 12, 24 and 36 months of cART, 3%, 5% and 8% of patients died in HCB, whereas 2%, 3% and 4% of patients died in RFH, respectively  initiated cART with prior AIDS diagnosed, while 337 (19%) of 1763 patients from RFH. Average baseline CD4+ T cell counts were significantly lower in Serbia than in UK (177 cells/mmectively .In south European countries, as a consequence of low testing rate, ARV treatment is introduced at an advanced stage of disease, having a high mortality rate as a consequence. Switching within ARV drugs appears often due to lack of drug supplies and frequently drug-related toxicity in south east Europe, while in the east European country due to patient's preferences and rarely due to drug-related toxicity.


Cardiovascular disease (CVD) is a leading health threat for HIV+ patients on antiretroviral therapy (ART); cardiometabolic comorbidities are key predictors of risk. Data are limited on incidence of metabolic comorbidities in HIV+ individuals initiating ART in low and middle income countries (LMICs), particularly for Hispanics. We examined incidence of diabetes and obesity in a prospective cohort of those initiating ART in the Dominican Republic.2, respectively. Dyslipidemia was total cholesterol ≥240mg/dl or use of lipid-lowering medication. Framingham risk equation was used to determine ten-year CVD risk at the end of observation.Participants ≥18 years, initiating ART <90 days prior to study enrollment, were examined for incidence of impaired fasting glucose (IFG), diabetes mellitus (DM), overweight, and obesity. Fasting plasma glucose (FPG) 100-125mg/dl defined IFG; FPG ≥126 mg/dl, diagnosis per medical record, or use of hypoglycemic medication defined DM. Overweight and obesity were BMI 25–30 and ≥30kg/mOf 153 initiating ART, 8 (6%) had DM and 23 (16%) had IFG at baseline, 6 developed DM (28/1000 person-years follow up [PYFU]) and 46 developed IFG (329/1000 PYFU). At baseline, 24 (18%) were obese and 36 (27%) were overweight, 15 became obese (69/1000 PYFU) and 22 became overweight (163/1000 PYFU). Median observation periods for the diabetes and obesity analyses were 23.5 months and 24.3 months, respectively. Increased CVD risk (≥10% 10-year Framingham risk score) was present for 13% of the cohort; 79% of the cohort had ≥1 cardiometabolic comorbidity, 48% had ≥2, and 13% had all three.In this Hispanic cohort in an LMIC, incidences of IFG/DM and overweight/obesity were similar to or higher than that found in high income countries, and cardiometabolic disorders affected three-quarters of those initiating ART. Care models incorporating cardiovascular risk reduction into HIV treatment programs are needed to prevent CVD-associated mortality in this vulnerable population. The advent of antiretroviral therapy (ART) has greatly increased life expectancy for people living with HIV (HIV+), but cardAlthough research in low and middle income countries (LMICs) has demonstrated increasing prevalence of diabetes and obesity in HIV+ individuals initiating antiretroviral therapy,–20 littlThe Dominican Republic (DR) is an ideal setting in which to examine the incidence of cardiometabolic complications after ART initiation. It is a resource-constrained country in the Caribbean with a high burden of obesity 26.6%), diabetes mellitus (9.9%), and dyslipidemia (12.3%), and CVD .6%, diabWe hypothesized that the known baseline increased risk of obesity and diabetes for HIV uninfected Hispanics in the U.S. could lead to increased risk of these conditions in HIV+ Hispanics receiving care in LMICs. We determine the incidence and overlap of key CVD risk factors: diabetes mellitus (DM), impaired fasting glucose (IFG), obesity, and overweight BMI in a longitudinal, prospective cohort of HIV+ patients initiating ART. We also examined the overall CVD risk and prevalence of cardiometabolic comorbidities. Our findings may have implications for ART expansion in LMICs, as cardiometabolic comorbidities would reduce the improvements in life expectancy offered by effective HIV treatment.Patients included in this analysis participated in the Dominican HIV Cohort, a prospective, observational cohort study of HIV treatment outcomes in the DR from September 1, 2007 through May 31, 2013. Continuous enrollment took place at two adult HIV treatment centers in Santo Domingo, Dominican Republic, participating in the Dominican national ART program. Physicians and patient educators in the clinic offered enrollment to individuals initiating or already receiving ART. Of those offered enrollment, approximately 75% accepted. The primary reasons for refusal were work conflicts or living at a distance from the clinic. The cohort population was representative of the general clinic population.Patients were included in this study if they initiated combination ART within 90 days prior to or any time after the first study visit. Patients were excluded if they had previously taken combination ART. Study patients were included in the analysis of DM and IFG if they had a baseline fasting plasma glucose (FPG) measurement ≤180 days prior to ART start date, and a second measurement ≥2 weeks after ART initiation. Non-pregnant study patients were included in the analysis of obesity and overweight BMI if measurements of height and weight were taken ≤180 days prior to or ≤30 days after ART start, and again ≥180 days after ART initiation. The distribution of cohort patients in the two analyses is represented in Our primary outcomes of interest for this study were incidence of: (1) DM or IFG, and (2) obesity or overweight BMI. DM was defined as at least one FPG ≥126 mg/dl, documented use of hypoglycemic medication, or DM diagnosis per the medical record, as in other studies in LMICs and other settings where confirmatory testing is not always available.–29 IFG w2 and overweight as BMI ≥25 kg/m2. Observation endpoint dates were the first date when patients met criteria for obesity, or the date of the last BMI if patients never met criteria for obesity. Twenty-four patients who were obese at baseline were excluded from the incidence analyses.Obesity was defined as BMI ≥30 kg/mDemographic variables included gender, age at the beginning of the observation period, and HIV transmission categories. Self-reported transmission categories were categorized as heterosexual sex, men who have sex with men (MSM), and other, including unknown or missing. No patients reported maternal to child transmission or injection drug use as HIV transmission risk.We calculated the years since HIV diagnosis at the beginning of the observation period, and the duration of HIV diagnosis from diagnosis to the endpoints of our primary outcomes. Immunologic status was categorized, based on CD4 count taken ≤180 days prior to and closest to ART start date (hereafter baseline CD4 count), as <200 or ≥200 cells per microliter. Baseline viral load status, based on HIV-1 RNA assay taken ≤180 days prior to and closest to ART start date, was unavailable for most of the cohort because pre-ART testing is not offered within the Dominican national program, but when available, was categorized as <1000 or ≥1000. Endpoint immunologic and virologic status were categorized, based on CD4 counts and HIV-1 plasma RNA assays measured within ±180 days from each endpoint, as <200 or ≥200 cells per microliter and <400 or ≥400 copies per milliliter, respectively. Exposure to ART, defined as the use of ≥2 NRTIs  with ≥1 PI (lopinavir/ritonavir) or 1 NNRTI (nevirapine or efavirenz), was calculated in months from the ART initiation date to each outcome endpoint. These were the only combinations of ART available, as first and second line treatment, through the Dominican national HIV treatment program. Months on PIs and NNRTIs were calculated from treatment initiation date of the drug class to each outcome endpoint.Dyslipidemia was defined as ≥1 measurement of total cholesterol ≥240 mg/dl, per the National Cholesterol Education Program (NCEP ATP III) guidelines, or documPatients were asked about use of tobacco, alcohol, and drug use every 6 months. Tobacco users were classified as current users or not current users, as per the Framingham CVD equation. Substance users were categorized as current users or non-current users throughout the observation period. Alcohol use was categorized as average number of drinks consumed per month over the observation period. Depression was defined as any positive response during the observation period to the Patient Health Questionnaire-2 (PHQ-2), administTen-year CVD risk scores were calculated at the end of observation with the Framingham CVD equation for those patients aged 30–74., 34 PatiBivariate analysis assessed associations between outcomes and the covariates above. Pearson Chi-square tests or Fisher’s Exact test tested associations between categorical variables. All continuous variables were non-normally distributed, so Mann-Whitney U tests determined differences in medians of continuous covariates by outcome. Survival analysis with Kaplan-Meier curves described incidence of DM, IFG, obesity, and overweight during the observation period. All analyses conducted 2-sided, with a significance cutoff of p<0.05 in IBM SPSS Statistics version 22  and R version 3.1.0 .Patients provided written informed consent prior to participating. The study protocol was approved by the Dominican National Committee on Bioethics (CONABIOS), the ethics committees of the Instituto Dermatológico y Cirugía de Piel “Dr. Huberto Bogaert Diaz” and Profamilia, and the Institutional Review Boards at Columbia University Medical Center and University of Texas Health Science Center at San Antonio.Of patients initiating ART within the cohort in 2007–2013, 140 met inclusion criteria for the fasting glucose analysis and 133 met inclusion criteria for the BMI analysis . The medOf 140 patients in the diabetes analysis, 8 (6%) had DM and 23 (16%) had IFG at baseline, defined henceforth as ≤180 days prior to starting ART. After ART initiation, 6 of 113 (5%) patients with either normoglycemic or IFG measurements at baseline developed DM, resulting in an incidence of 28 per 1000 PYFU . Forty-s2. Few patients lost weight after becoming obese or overweight; eight patients went from obese to overweight, no obese patients reached a normal BMI (<25 kg/m2), and ten patients went from overweight to a normal BMI by the end of observation. However, whether this weight loss was intentional is difficult to determine. Considering changes in weight, at the end of observation, 24% of the cohort was obese and 42% was overweight.Of 133 patients in the obesity analysis, 24 (18%) were obese and 36 (27%) were overweight at baseline. At least 6 months after initiating ART, 15 (15%) patients became obese from normal or overweight BMIs, resulting in an incidence of 69 per 1000 PYFU . Twenty-Framingham ten-year year risk scores were calculated for the 82 patients >30 years of age, with a median age of 42.4 (IQR: 38.2–50.6) at the time of score calculation. Two (2%) patients were classified as high risk (>20%), and nine (11%) were at moderate risk (10–20%). Two individuals suffered cardiovascular events during the observation period and were excluded from risk calculations. Thirty (20%) patients met criteria for hypertension, twenty (67%) of whom were receiving anti-hypertensive medication. Of those receiving treatment, seven (35%) patients had uncontrolled blood pressure, >140/90 (or 130/80 for diabetics) at their last measurement.Thirty-five (24%) of 143 patients who had lipid panels measured during observation had dyslipidemia based on serum lipid measurements or use of lipid-lowering medications. Analysis of the overall prevalence of cardiometabolic multi-morbidity  revealed 79% of the cohort had at least one cardiometabolic comorbidity, 48% had two or more, and 14% had all three . SeventyIn this first study to determine incidence and predictors of new onset impaired fasting glucose, diabetes, overweight, and obesity following ART initiation in a longitudinal observational cohort in Latin America, we find a high incidence of these outcomes, most of which occurred within the 12 months following ART start. There was also a 13% prevalence of elevated CVD risk per the Framingham risk score, and a striking degree of overlap between cardiometabolic comorbidities, with the vast majority (79%) having at least one risk factor and almost half (48%) having two or more metabolic risks. These data have direct implications for HIV treatment programs in the region, and indicate that they should plan for an increase in metabolic and cardiac risk in many of those initiating ART.The incidence of insulin resistance that we found in our cohort is concerning, as impaired fasting glucose was observed in almost half of our cohort in a span of two years, despite the fact that very few patients 13%) were receiving protease inhibitors, which are traditionally associated with this phenomenon,% were re, 35 but The reported incidence of DM among HIV+ individuals in high income countries ranges from 4.42 to 47 cases per 1000 PYFU, placing the incidence seen in our cohort (28/1000 PYFU) at the high end of that seen in high income settings., 29, 35 Research has demonstrated rising prevalence of obesity in HIV+ cohorts in high income countries, however,Using the Framingham CVD risk calculator to assess ten-year cardiovascular risk in the cohort, we found a 13% prevalence of elevated CVD risk. This is higher than other studies of HIV+ individuals in LMICs: 10.7% in Nigeria, 9.9% in Thailand, and 3.6% in Uganda, but comparable to the 11–18% prevalence found in a study of HIV negative individuals in Latin America., 50–52 TCertain limitations should be noted. The ADA suggests using two FPG to diagnose DM, but a confirmatory measurement was not routinely available in this LMIC. However, prior studies have reported DM incidence using one FPG measurement.–29 Many Our findings of high incidence of diabetes and obesity after ART initiation have significant clinical implications for the management of care for HIV+ patients in Latin America. It is concerning that, after a median 24 months on ART, over half the cohort met criteria for IFG or DM, and half were overweight or obese. The burden of metabolic comorbidity is worrisome as a majority (87%) of these patients was receiving NNRTI-based regimens, which are less associated with insulin resistance than PI-based regimens. Many programs providing HIV care in LMICs, including those in the DR, are “silo-ed” into clinics focused on HIV treatment, and not integrated with primary care. Our findings demonstrate missed opportunities for lipid control, hypertension control, and lifestyle interventions that could reduce risk for obesity and DM. Given the rapid development of IFG/ DM and overweight/obesity after ART initiation, and the high prevalence of overlapping cardiometabolic risks in this cohort, we advocate for the integration of assessment and treatment of cardiovascular risk into HIV care.This increased risk for CVD is particularly important in Latin American settings, as cardiovascular risk is highly prevalent in the general population and is a significant cause of mortality in the region.–23 If thS1 Data SetVariable definitions are included in second sheet.(XLSX)Click here for additional data file.


P = 0.069) and 480 to 830/μL . Five patients (2 in uVL and 3 in dVL) improved their immunological status from moderate to no immunosuppression. Serum lipid profiles improved in both groups; cholesterol dropped significantly in the dVL group (P = 0.008). Grade 1 laboratory adverse events (AEs) were observed in 3 patients. No clinical AEs occurred. Adherence was complete in 9 patients (5 in uVL and 4 in dVL); 1 adolescent interrupted treatment. Once-daily STR with RPV/FTC/TDF may be a safe and effective choice in selected HIV-1-infected adolescents and children.To assess the safety and efficacy of rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily single-tablet regimen (STR) in HIV-1-infected children and adolescents we performed a multicenter case series study of HIV-1-infected patients. Inclusion criteria were initiation of therapy with RPV/FTC/TDF before the age of 18. Patients were divided into undetectable viral load (uVL) group, HIV-1 RNA < 20 copies/mL on stable combined antiretroviral therapy (cART), and detectable viral load (dVL) group, HIV-1 RNA ≥ 20 copies/mL at RPV/FTC/TDF initiation. Patients were monitored from the date of RPV/FTC/TDF initiation until June 30, 2015, RPV/FTC/TDF discontinuation or failure to follow-up. Seventeen patients (8 in uVL and 9 in dVL group) with age between 11.6 and 17.6 were included. Reasons for switching were toxicity (n = 4) and simplification (n = 4) in uVL; viral failure (n = 8) and cART initiation (n = 1) in the dVL group. After a median follow-up of 90 (uVL) and 40 weeks (dVL), 7/8 (86%) patients maintained and 8/9 (89%) achieved and maintained HIV-1 suppression. Median CD4 count increased from 542 to 780/μL (uVL,  Furthermore, lack of adherence (particularly in adolescents), high pill burden, inadequate support, substance abuse, few age-appropriate formulations to ensure appropriate drug exposure, and differences in pharmacokinetics between children and adults impact efficacy and safety. STR also avoid selective nonadherence—not taking all components of a regimen. Rilpivirine (TMC278), a new non-nucleoside reverse transcriptase inhibitor (NNRTI), is available as a single-agent tablet or in combination with FTC plus TDF in an STR. Several studies have indicated RPV/FTC/TDF STR being a favorable choice in naïve and selected treatment-experienced HIV-1-infected adults.–12 This STR has been approved by the FDA in naïve HIV-1-infected adults with HIV-1 RNA ≤100,000 copies/mL or virologically suppressed (HIV-1 RNA < 50 copies/mL) adults with no mutations associated with resistance to NNRTIs, FTC, or TDF.In adults, single-tablet regimens (STR) are associated with high adherence rates and improvement of quality of life.,15 Here, we present long-term data from children and adolescents with perinatally acquired HIV-1 infection treated with off-label RPV/FTC/TDF.RPV has been approved in the United States for children age ≥12 years, but not in Europe, and data on its efficacy in this age group is very limited to date. PAINT (Pediatric study in Adolescents Investigating a new NNRTI TMC278) is a multicenter ongoing trial evaluating the pharmacokinetics, safety, and efficacy of RPV in treatment-experienced and naïve HIV-1-infected adolescents age 12 to 18 years.1.1 see Annex). STR with RPV/FTC/TDF (25/200/245 mg) was prescribed under the Spanish off-label medication use program. Individuals were monitored from baseline (date of RPV/FTC/TDF initiation) until June 30, 2015 (administrative censoring date), RPV/FTC/TDF discontinuation or failure to follow up. Demographic, clinical, and laboratory parameters were extracted from the CoRISpe database. Adherence was evaluated by pill count, assessing the dose taken, and interviewing parents/guardians, and was summarized as a single percentage for each combined antiretroviral therapy (cART) regimen for each patient and categorized as poor (<70%), intermediate (70–90%), good (91–99%), or perfect (100%). Immunological category and clinical stage were based on the CDC classification. Major mutations from the IAS-USA mutation list 2013 were used to define resistance to RPV, TDF, and/or FTC. Plasma VL (HIV-1 RNA) was measured by Amplicor Monitor assay  and real-time NASBA  with a detection limit of 20 HIV-1 RNA copies/mL. Virological failure was defined as the inability to achieve or maintain suppression of viral replication below 20 copies/mL. CD4 were quantified by flow cytometry . Toxicity was monitored every 6 months during follow-up. Parameters monitored included renal toxicity, hepatic toxicity, and laboratory parameters such as lipid profile cholesterol and glucose. Rash, dizziness/light-headedness, insomnia or abnormal dreams, headaches, nausea, fatigue, and depression were also evaluated. Adverse events (AEs) severity was graded using the Division of AIDS AEs grading table. Ethical approval was obtained from the ethical committees of all hospitals.In this multicenter observational study, 17 vertically HIV-1-infected children and adolescents (<18 years) were enrolled from March 2013 from 6 pediatric reference hospitals .Quantitative variables were summarized using medians and interquartile ranges (IQRs), whereas absolute values and relative frequencies were used for qualitative variables. Demographic, clinical, and laboratory variables were analyzed according to baseline VL: patients with undetectable VL (uVL) and patients with detectable viral load (dVL). Continuous variables were compared between groups using the Mann–Whitney 2Seventeen subjects were included in the study. Demographic, clinical, and laboratory baseline characteristics are summarized in Table P = 0.01). Seven out of 8 adolescents with uVL at baseline (including the 3 patients with RAMs) maintained undetectable viral load (uVL) for a median time of 93.6 weeks (IQR: 87.4–104.3). A 17-year-old boy developed viral failure due to poor adherence (<10%) caused by mental disorders . Eight out of 9 patients in the dVL group achieved and maintained uVL for a total median time of 41.1 weeks (IQR: 26.8–57.5), although 1 of these experienced a blip at the end of the follow-up because of intermediate adherence (50–90%). On the other hand, 1 adolescent remained persistently detectable during the study period because of poor adherence (<70%) and low-level TDF resistance (T215Y), while the patient who had the T215Y and Y181C mutations reached a viral load below 100 copies/mL (77 copies/mL) after 30.9 weeks.Reasons for RPV/FTC/TDF initiation were simplification ; toxicities ; viral failure  and CD4 count below 350/μL in the naïve patient. Overall median time on RPV-based treatment was 61.9 weeks (IQR: 41.1–90.5). According to baseline VL, 8 patients were included in the uVL group and 9 subjects were included in the dVL group. Median time on RPV-based treatment was 89.1 weeks (IQR: 66.5–100.9) and 39.6 weeks (IQR: 23.6–55.4) in the uVL and dVL groups, respectively . Five patients changed their immunological category from moderate immunosuppression to no suppression (29%); however, 1 patient dropped from category 1 to 2. No patient discontinued the study because of AEs. Grade 1 AE were reported in 3 patients (18%). Increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) occurred in 2 adolescents (12%), although in 1 of them it was not considered related to RPV-based treatment, and triglycerides elevation was reported in 1 patient (6%). While lipid profile in the uVL group improved, it did not reach statistical significance. On the other hand, in the dVL group, cholesterol (P = 0.01) improved significantly. Clinical AE related to RPV/FTC/TDF, such as skin rash or central nervous system-related symptoms were not observed during follow-up. Moreover, the 2 adolescents who had suffered insomnia or abnormal dreams with their previous EFV-based regimen did not report any complaints with the new cART. One adolescent with poor adherence (<70%) discontinued the RPV-based regimen and dropped out of care. No deaths were observed.Laboratory parameters are summarized in Table 3,10 As previously described, it is also worth noting that we observed an improvement of fasting serum lipid profile.In this case series of HIV-1-infected children and adolescents, treatment with RPV/FTC/TDF was associated with good control of HIV infection in both groups (uVL and dVL) after a median follow-up time of 89.1 and 39.6 weeks, respectively, in all but 2 patients with a poor adherence (<70%). While no clinical or laboratory significant adverse effects were observed, CD4 counts and CD4/CD8 ratio improved independently of the study groups. These observations are in line with previous publications in adults comparing RPV with EFV therapy, which describe a significant increase in CD4 counts after the 96-week treatment period in the RPV group. In this study, Grade 1 AST/ALT and triglycerides elevation were the only laboratory abnormality observed.Only low-grade AEs were reported during clinical follow-up and the toxicities that lead to cART switch to RPV/FTC/TDF  disappeared. AST, ALT, and creatinine were the commonest observed Grade 3 to 4 laboratory abnormalities described in adults.In summary, in this first pediatric study, RPV/FTC/TDF was associated with control of viral replication, an improvement of CD4 counts and CD4/CD8 ratio as well as serum lipid profiles, while low-grade AEs were observed. An important limitation of this observational study is the small sample size as well as the different time for follow-up between the 2 groups. However, to date there is limited data on adolescent patients and no data regarding children receiving RPV/FTC/TDF therapy. Our observation is therefore new and probably reassuring, although the presented results need to be confirmed with larger prospective clinical studies in order to conclude whether RPV/FTC/TDF is a good therapeutic option in selected HIV-1-infected children and adolescents where treatment simplification strategies to enhance adherence are crucial.4Hospitals in which the patients were enrolled: Hospital Virgen del Rocío, Seville (6 patients); Hospital Universitario Doce de Octubre, Madrid (2 patients); Hospital Universitari Vall d’Hebron, Barcelona (4 patients); Hospital Sant Joan de Déu, Barcelona (3 patients); Hospital General Universitario Gregorio Marañón, Madrid (1 patient); and Hospital Virgen de las Nieves, Granada (1 patient).


Many studies have shown the superiority of single tablet regimens (STRs) of antiretrovirals for the treatment of HIV in terms of efficacy, adherence and rate of hospitalisation as they offer a low pill burden and once daily dosing. Our objective was to compare the duration of first-line STRs to multi-tablet regimens.From our clinical database, we selected patients initiating any of the major first-line regimens between 2007 and 2013. Two STRs, Atripla (ATP) and Complera (CPLR), were compared to three non-STRs: two NRTIs and raltegravir (RAL), atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r). The primary outcome was time to discontinuation of the first-line regimen. The association between regimen type and duration was estimated using Cox proportional hazards models adjusted for age, gender, baseline CD4, baseline viral load, risk factor, site and year of treatment initiation.A total of 743 patients (281 on STRs and 462 on non-STRs) were included. 693 (93%) were male and median age was 43 years. Median length of follow-up was 3.2 years. 56% of patients were MSM, 6% IDU and 6% from endemic countries. Patients on an STR were less likely to be IDU (p<0.024) and have a baseline HIV-RNA ≥100,000 copies/mL (p<0.011). Overall, 321 (43%) patients discontinued their regimen during the study period. The rate of discontinuation one year after starting ARV depends on the regimen: 29% for patients on 2NRTIs+DRV/r, 26% on ATP, 25% on 2NRTIs+ATV/r, 17% on 2NRTIs+RAL and 10% on CPLR (p<0.001). In the adjusted model, durability for STR and non-STR was equivalent . Compared to patients on ATP, patients on CPLR were less likely to discontinue . No difference between ATP and the other regimens was observed: HR for 2NRTIs+RAL=0.92 (p=0.66), 2NRTIs+ DRV/r=1.16 (p=0.36), 2NRTIs+ATV/r=1.11 (p=0.46).Our findings suggest that STRs do not necessarily result in a more durable treatment. Even with a higher pill burden and/or twice daily dosing, patients initiating therapy with RAL or boosted-PI based regimens were not more likely to discontinue the first-line regimen compared to patients on an STR. Among the STR subgroups, the regimen with better known tolerability conferred more durable treatment. Limitations included our inability to adjust for the patient's adherence to a given regimen.


Antiretroviral therapy has significantly expanded and an increased proportion of patients have switched to second-line regimens in China. We describe the outcomes of second-line therapy among patients having received long-term first-line ART. A prospective follow-up study was conducted in rural areas in China. We compared the virological, immunological outcomes and genotypic drug resistance (DR) profiles before and after regimen switches. A total of 303 patients were enrolled, 283 (93.4%) were retained at 12 months. Of 90 participants with HIV-RNA ≥ 1000 copies/ml before switch, the proportion of viral load (VL) ≥ 1000 copies/ml at 6 and 12 months was 49.4% and 43.9%, respectively. Of 213 patients with HIV-RNA < 1000 copies/ml before switch, the proportion of VL ≥ 1000 copies/ml at 6 and 12 months was 4.8% and 6.5%, respectively. The rates of drug resistance to NNRTIs, NRTIs, PIs decreased from 65.5%, 53.3%, and 1.1% before regimen switch to 26.8%, 18.3%, and 0% at 12 months, respectively. DDI-based initial ART regimens and missing doses in past month were associated with HIV RNA ≥ 1000 copies/ml at 12 months. The results showed that patients having received long-term first-line ART and experiencing virological failure had good virological outcomes after switching to second-line treatment in China. The rapid scale-up of combination antiretroviral treatment (cART) over the past decade has resulted in dramatic reductions in morbidity and mortality for patients infected with HIV/AIDS1234893, and this CD4 threshold increased to 350 cells/mm3 in 2012. The threshold CD4 cell count further increased to 500 cells/mm3 in 2014, and the role of ART in public health programs was strengthened in the treatment and prevention of HIV infections, in accordance with the WHO 2013 consolidated guidelines. Besides CD4 counts, disease progression, and the status of TB, HBV and HCV coinfections are also taken into account to decide when to start cART. ART Initiation is recommended in HIV-infected individuals who are pregnant women, in HIV-serodiscordant couples, in those with active TB disease, or with severe chronic liver disease, regardless of CD4 cell count. During ART, CD4 cell count testing is done every 6 month, and plasma viral load is quantified at least once a year. In addition, hepatic function is monitored at months 0, 0.5, 1, 2, 3, 6 of cART, and every 6 months thereafter. The first-line regimens are composed of two NRTIs and one NNRTI, which were ddI-based as AZT/d4T + ddI + NVP/EFV before 2005, and 3TC-based as AZT/d4T + 3TC + NVP/EFV since 2005, and AZT/TDF + 3TC + EFV/NVP since 2012. In case of HIV/HCV coinfection, treatment decision is made based on CD4 cell count and hepatic function. Initiation of ART is recommended prior to starting the treatment for HCV when CD4 cell count is below 200 cells/mm3, and HCV treatment is recommended before the initiation of ART when CD4 cell count is ≥350 cells/mm3, or when CD4 cell count is 200 to 350 cells/mm3 and with elevated liver enzymes. In addition, antiretroviral drugs with less hepatoxicity should be chosen, and the recommended regimen is TDF + 3TC + EFV/(LPV/r)After a pilot cART program among former plasma donors in 2002, China has scaled up the National Free Antiretroviral Treatment Program (NFATP) rapidly since 2003. Enormous efforts have been made to develop the capability of treating large numbers of people across wide geographic areas, including training rural healthcare workers. According to the NFATP guidelines, the baseline evaluation including CD4 cell count, complete blood count, transaminase levels, TB test, and serologic test for HBV and HCV should be performed before the initiation of combined antiretroviral therapy (cART). Since 2003, patients started cART when the CD4 cell counting was below 200 cells/mmBy the end of January 2014, more than 281, 873 patients across the country have received free antiretroviral treatment121415Among 320 consecutive patients enrolled, 17 patients were excluded from this study, including two who were less than 18 years old, ten who received first-line treatment for less than 12 months, and five patients who did not switch to second-line antiretroviral drugs. Totally, 303 subjects entered this prospective cohort. Blood samples for testing viral load and drug resistance were collected from all patients within a month before switching drugs (baseline). The characteristics of these patients at baseline are shown in 2 = 61.09, p < 0.0001). It was notable that a substantial proportion of patients were with VF but not detectable drug resistance at 6 months  and 12 months  of regimen switch. For those with HIV-RNA <1000 copies/ml at baseline, the rate of HIV/HCV coinfection was 86.8% (185/213), and the proportion of patients with VF was 4.8%, 6.5% at 6 and 12 months of switching to second-line regimen, respectively . Among those patients with viral load ≥1000 copies/ml at 6 and 12 month, 60.0% (6/10) and 69.2% (9/13) had not detectable drug resistance, respectively. The patients with VF at switch had much higher rates of drug resistance at 6 and 12 months than those patients with HIV RNA < 1000 copies/ml at baseline , and there was also significant difference in the proportion of VF after switching to second-line at 6 and 12 months between these two groups .Among the 303 participants, 90 participants had plasma HIV viral load ≥1000 copies/ml and 213 patients with viral load <1000 copies/ml at baseline . Of the 2 = 43.12, p < 0.0001). Twenty-eight patients had constant VF at baseline and after 6 and 12 months of regimen switch. Disregard of the existence of drug resistance at switch, the rates of VF was dramatically decreased among the patients with baseline VF after 6 and 12 months .Among 60 patients with drug resistance at baseline , the proAmong the 213 patients with viral load <1000 copies/ml before switching regimens, 24 (11.3%) had CD4 < 200 . Among tpol region. Based on phylogenetic analyses, two (2.2%) of them harbored B/C unique recombinant forms (URFs) HIV-1 strains; others had Thai B (B’) viruses. At baseline, 60 (66.7%) patients had drug resistance, and the proportion of drug resistance to NNRTIs, NRTIs, and PIs were 65.5%, 53.3%, and 1.1%, respectively. Commonly observed NRTI-related mutations were 3TC related M184V mutation (48.9%), Thymidine analogue such as AZT/d4T associated mutations (TAMs) like T215YSF (34.4%) and M41L (21.1%), non-thymidine analogue such as DDI related K65R mutation (1.1%), and L74V (1.1%). 31.1% of the patients had at least 2 TAMs. The most frequent NNRTI-related mutations included K103NS (38.9%), Y181CY (22.2%), G190A (14.4%). A PI-related mutation, I54V, was found in one patient. One of the two patients with B/C URF harbored multiple DR mutations, including NRTI-related mutations as D67N, K70R, M184V, and K219E, which conferring high resistance to 3TC, and low resistance to TDF, and NNRTI-related mutations as E138Q, V179D, and G190Q, causing high resistance to all current available NNRTIs. One year after switching to second-line ART among the same individual, 36 (43.9%) patients had plasma HIV RNA ≥ 1000 copies/ml, and the proportion of drug resistance to NNRTIs, NRTIs, and PIs were 26.8%, 18.3%, and 0%, respectively. The proportion of patients having at least 2 TAMs was 17.3%, 13.4%, respectively, at 6 and 12 months. Of the 28 patients who were with constant VF, and were mentioned above, two patients did not harbor drug resistance mutants at baseline but developed drug resistance at 12 month after the switch to the second line drugs, 11 patients did not have drug resistance at all the three time points, and the remaining 15 patients had detectable drug resistance at the three time points, five of these 15 patients have at least one more TAMs mutation, and one of the 15 patients developed a 3TC related M184V mutation. The patient with drug resistance B/C URF was lost of follow up at 6 months, and had plasma HIV RNA > 1000, but without drug resistance at 12 months. The other patient with B/C URF without detectable drug rsistance at baseline achieved viral suppression at both 6 and 12 months. Ninety samples from participants with VF at baseline were genotyped with partial Factors significantly associated with HIV RNA ≥ 1000 copies/ml after switching to second-line ART at 12 months are shown in In this one-year prospective cohort, we found that among 90 patients who switched to a second-line regimen with viral load ≥1000 copies/ml, 43.9% had HIV RNA ≥ 1000 copies/ml 12 months later. The rate of virological failure in this study was substantially higher than what was reported in other low-resource settings1920232425The patients in this study were the first groups of patients receiving the first line cART drugs in China. Among the patients with VL < 1000 copies/mL who switched to the second-line regimens, 86.9% (185/213) were HCV antibody positive. In case of HIV/HCV co-infection, TDF + 3TC + EFV/(LPV/r) is recommended by the NFATP guidelines. Even though all the patients had an HCV antibody test, the second-line drugs had been unavailable for many years after the initiation of their cART. Among the 185 patients, 56.8% had received DDI-based regimen as their initial treatment, and 41.6% had received AZT-based or D4T-based regimen. The other 28 patients demanded to switch to second-line regimen, because they believed that the second-line regimens could better control the virus and have fewer side effects. We found that a small proportion of the patients with VL < 1000 copies/ml at regimen switch, had viral load rebounded to above 1000 copies/ml. However, it’s notable patient with lower CD4 counts seems more likely to experience virological failure after switching. Comparing two groups with different viral load levels before switching, Patients with viral load <1000 at regimen switch had much lower proportions of virological failure  and drug resistance at 6 and 12 months of regimen switch than other patients with viral load ≥1000 at switch. However, the long-term benefit of earlier second-line switch is still not clear. More studies are needed to clarify the optimal switch criteria.In this study, the majority of the patients who were former plasma donors (FPD), with VF at baseline were infected with B’ HIV-1 strains. The distribution of HIV-1 subtypes among FPD is consistent with the findings found in a cross-sectional national molecular survey27>1000 copies/ml before and after switching to second-line for 6, and 12 months was 100%, 48.1%, 41.8%, respectively, of 30 patients without drug resistance the proportion was 100%, 51.8%, 48.1%, respectively. Although these two groups had experience virological failure before switching drugs, the rate of viral suppression both decreased, and there was no statistical difference. Despite of drug resistance at baseline, the rate of drug resistance decreased and the proportion of VL < 1000 copies/ml increased after switching to second-line regimens. Our study showed that the switch to second-line therapy in patients with long-term treatment and drug resistance led to effective viral suppression again, although drug resistance to NRTIs widely exists, especially drug resistance mutations such as M41L, T215Y, and TAMs, has a great influence on TDF sensitivity in second-line drugs2032Among 90 patients with virological failure before treatment switch, the rate of drug resistance to NNRTIs, NRTIs, PIs was 65.5%, 53.3%, 1.1%, respectively, and the multi-drug resistance to both NNRTIs and NRTIs was 52.2%. After switching regimens for 12 months, 22 cases (26.8%) displayed NNRTI mutations and 15 cases (18.3%) displayed NRTI mutations. Although one patient harbored PI-related I54IV mutation before switching, no PI-related mutation was identified after 12 months. As this patient did not have any experiences of treatment with PIs before switching regimen, the I54V mutation might occur naturally as a polymorphism, and disappeared after the second-line treatment. Of 60 participants with drug resistance before switching regimens, the proportion with viral load  1000 copies/ml) 12 months after switching to second-line ART in China. Adherence remains as a significant risk factor affecting viral suppression, and these results are similar to those obtained in other developing countries35Our study found that DDI-based initial ART regimen, and missed doses in the month prior to switching were independently associated with virological failure  experienced virological failure before regimen switch, so conclusions should be drawn with caution. Second, due to the limited geographic distribution of the surveillance sites and exclusion criteria, these results may not be fully representative of HIV/AIDS patients in China. More data are needed, particularly for patients receiving long-term treatment, to better understand outcomes after switching regimens. Third, due to the small sample size, the HIV cumulative drug resistance rate after receiving first-line therapy for a median of 89 months is likely lower than the true drug resistance rate. Finally, an one-year follow up survey is relatively short for the purposes of assessing outcomes after switching to second-line therapy for patients receiving long-term first-line treatment, and more studies with long-term monitoring are recommended to provide more accurate data on viral suppression, and HIVDR profiles.In summary, this 12-month prospective study demonstrates good virological outcomes after switching to second-line treatment for patients having received long-term first-line treatment and experiencing virological failure at the time of switching regimens. However, for patients with viral load <1000 copies/ml, switching to second-line treatment is not clearly beneficial, and more studies are needed to clarify the optimal switch criteria. The poor adherence is associated with an increased risk for poor virological response.Three sentinel surveys were conducted in rural areas of China, including Weishi county, Xincai county and Queshan county of Henan province, where ART began earlier and there were a large of patients having received long-term first-line regimen. These areas have high rates of HIV drug resistance (HIVDR). The study was a prospective cohort study with follow-up at 6 and 12 months after switching to second-line regimens. Study subjects were recruited at the time of switching to second-line therapy at each clinic. Criteria for enrolling in the study were: previously receiving first-line therapy for at least 12 month, 18 years or older, having national ART patient ID, switching to second-line regimen, and willing to provide informed consent. A baseline screening survey was conducted between April 2012 and November 2012 before switching antiretroviral drugs. ART regimens were provided through the NFATP. Second-line ART regimens consisted of tenofovir (TDF) + lamivudine (3TC) + lopinavir and ritonavir (LPV/r). Based on WHO guideline, we defined viral load ≥1000 copies/ml as virological failure. The main study outcome was HIVDR variation after switching regimens. Specific objectives were to: (1) estimate changes in the proportion experiencing virological failure, drug resistance and immunological failure after switching second-line ART; (2) study factors associated with virological failure after switching second-line ART at 12 months.The study was approved by the institutional review board (IRB) at the National Center for AIDS/STD Control and Prevention of the China Center for Disease Control and Prevention . All experimental protocols were approved by IRB at NCAIDS, China CDC, according to the international and Chinese ethical guidelines, and the methods were carried out in accordance with the approved guidelines.Data were collected using an interviewer-administered questionnaire. The questionnaire was administered by trained interviewers in a local clinic room. Questionnaires included demographic data, ART treatment and self-reported adherence data. Demographic variables included age, sex, marital status and HIV transmission route. ART treatment variables included initial regimens, duration of first-line treatment. Self-reported adherence variables included emotional support, missed ART doses in the past month, the ratio of on-time drug intake in the past month, and any regimen terminations in the past month.http://hivdb.stanford.edu/pages/algs/sierra_sequence.html). Any drug resistance mutations, whether conferred low-, intermediate-, or high-level, were defined HIVDR mutations3940All subjects provided blood specimens before switching drugs and at 6 and 12 months after switching to measure CD4+ T-lymphocyte count (CD4 count), HIV viral load, and HIV drug resistance mutations. HCV antibody test just done before switching drugs. CD4 count was measured using flow cytometry  within 24 hours after specimen collection in local CDC facilities. Plasma was isolated by centrifuge and stored frozen at −80 °C at local CDC facilities before transferring to NCAIDS in Beijing for measuring viral load and drug resistance mutations. Plasma HIV RNA was quantified with real-time NASBA  according to the manufacturers’ recommendations. Successful viral suppression was defined as HIV RNA level < 1000 copies/ml. If viral load ≥1000 copies/ml, HIVDR genotyping was performed by an in-house polymerase chain reaction at the WHO Accreditation Laboratory of NCAIDS, China CDC37EpiData software  was used for data entry. Data were double-blinded entered and compared. Questionnaire and laboratory data were analyzed using Statistical Analysis System version 9.1 . Unadjusted odds ratios were computed and tests for significance were based on chi-square and Fisher’s exact tests. Variables that were significantly (p < 0.05) associated with HIV RNA ≥ 1000 copies/ml at 12 months in the univariable analyses were considered for inclusion in the multivariable logistic regression model. Multivariable logistic regression was performed to examine the independent effect of each factor under consideration. P-values < 0.05 were considered statistically significant, and all tests of significance were two-sided.How to cite this article: Wang, J. et al. Efficacy and HIV drug resistance profile of second-line ART among patients having received long-term first-line regimens in rural China. Sci. Rep.5, 14823; doi: 10.1038/srep14823 (2015).


As CD4/CD8 ratio inversion has been associated with non-AIDS morbidity and mortality, predictors of ratio normalization after cART need to be studied. Here, we aimed to investigate the association of antiretroviral regimens with CD4/CD8 ratio normalization within an observational cohort.We selected, from a French cohort at the Nice University Hospital, HIV-1 positive treatment-naive patients who initiated cART between 2000 and 2011 with a CD4/CD8 ratio <1. Association between cART and ratio normalization (>1) in the first year was assessed using multivariate logistic regression models. Specific association with INSTI-containing regimens was examined.567 patients were included in the analyses; the median CD4/CD8 ratio was 0.36. Respectively, 52.9%, 29.6% and 10.4% initiated a PI-based, NNRTI-based or NRTI-based cART regimens. About 8% of the population started an INSTI-containing regimen. 62 (10.9%) patients achieved a CD4/CD8 ratio ≥1 (N group). cART regimen was not associated with normalization when coded as PI-, NNRTI- or NRTI-based regimen. However, when considering INSTI-containing regimens alone, there was a strong association with normalization .Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in naïve patients. Should it be confirmed in a larger population, it would be another argument for their use as first-line regimen as it is recommended in the recent update of the “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents”. In parallel, the deleterious effect of activated cytotoxic CD8 cells has been recognized  and a larger population would have most probably affected the CI95% of the OR but not the direction of the association even if we cannot definitively rule-out the possibility of an allocation bias secondary to a small selected subgroup of patients receiving raltegravir. This has been, at least partly, taken into account through the multivariate analysis with adjustment on variables associated with ratio normalization. Longer follow-up could have allow to observe higher rate of normalization as studies have found a median delay to ratio normalization ranging from 3 to 10.1 years , 14. HowOur findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year. This result is assessed on a population unselected on viral load, naïve of ARV, so effect of INSTI-class is not confounded by prior ARV treatment, in “real life condition”. However this should be confirmed on a larger naïve population, receiving all INSTI drugs, with an extended follow-up to draw firm conclusions. Our results support the recent update of the “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents”  that lar


Many HIV-1-infected patients on suppressive antiretroviral therapy (ART) have transiently elevated HIV RNA levels. The clinical significance of these viral blips is uncertain. We have determined the incidence of blips and investigated important associations in the Swedish HIV-cohort.HIV-1-infected ART naïve adults who commenced ART 2007–2013 were retrospectively included. Viral blips were defined as a transient viral load between 50 and 500 copies/mL Subjects not suppressed after six months on ART were excluded.10 4.85 copies/mL) compared with subjects without blips (median log10 4.55 copies/mL) (p < 0.01). There was a significant association between viral blips and risk for subsequent virological failure (p < 0.001).Viral blips were found in 76/735 included subjects (10.3 %) and in 90/4449 samples (2.0 %). Median blip viral load was 76 copies/mL (range 56–138). Median follow-up time was 170 weeks (range 97–240). Baseline viral load was higher in subjects with viral blips . Blips were associated with high baseline viral load and an increased risk of subsequent virological failure. Most patients on combination antiretroviral therapy (cART) reach the goal of therapy, HIV RNA < 50 copies/mL blood, within three to six months after initiation of cART , 2. WhenEven though the plasma viral load is suppressed to < 50 copies/mL in a majority of treated patients, it may increase to detectable levels from time to time, usually to a maximum of 500 copies/mL, before decreasing to < 50 copies/mL again, so called viral blips . There m+ T-cell count, pre-treatment viral load, choice of cART, and some co-morbidities.Possible consequences of viral blips are not clear. Some studies have found a correlation between viral blips and subsequent virological failure –20, wherAs part of clinical care, > 99 % of HIV-1-infected individuals living in Sweden are followed from diagnosis and onwards using a clinical decision support tool, called InfCare HIV. Clinical data from InfCare HIV is transferred in real time to a research database. All demographic data, all HIV RNA levels, all CD4+ T-cell counts, all ART regimens the patient has ever been on, are registered in the database. In this retrospective study, we included subjects matching our inclusion criteria. Participants had to be HIV-1-infected adults (≥18 years old) receiving their first line of cART and they had to have been on treatment for at least six months with at least one HIV RNA value < 50 copies/mL to secure treatment response before data was collected. The included patients were from five of Sweden’s largest HIV-clinics . These five clinics account for approximately two thirds of all HIV-1-infected patients in Sweden. Subjects were followed from August 2007 to December 2013 in two clinics (596 patients), and from June 2009 to December 2013 in the remaining three clinics (139 patients). The different starting dates for inclusion was because the ethylene diamine tetraacetic acid (EDTA) test tubes and the highly sensitive COBAS TaqMan HIV-1 technique , with a lower detection limit of 40 and 20 copies/mL (version 1 and 2), respectively, were introduced at different time-points at the different clinics. All patients at these clinics are followed according to the Swedish guidelines for treatment of HIV-1 infection. After initiation of cART, plasma HIV RNA is followed after 3 and 6 months, and after that every third to sixth months depending on the patient and the clinician.Viral blips were defined as transient plasma HIV RNA levels between 50 and 500 copies/mL preceded and followed by HIV RNA < 50 copies/mL. Two values within six weeks apart were interpreted as one isolated blip where the highest HIV RNA level was noted. Patients were excluded if they had a viral failure, defined as a single HIV RNA measurement > 500 copies/mL or two consecutive samples ≥ 50 copies/mL drawn more than six weeks apart. Treatment interruptions of shorter than one month caused a pause in data collection for six months from the reinitiation of ART. If the interruption was longer than one month no more data was analysed after the interruption. If the last registered sample was 50–499 copies/mL this data was excluded to avoid confusion between possible blips and viral failure.Samples with HIV RNA levels between 20 and 50 copies/mL were registered separately unless they were taken within six weeks from a blip and thus interpreted as part of the transient viremia. Demographic and medical data were collected, and included country of origin, age, gender, source of transmission, ethnic background, date of diagnosis and start of treatment, treating clinic, baseline viral load (VL) sampled within one month before treatment initiation, CD4 nadir, baseline primary drug-resistance mutations, choice of cART, co-infections with hepatitis B and/or C, and the presence or not of AIDS-defining conditions. Treatment regimen was registered for each blood sample during the study period.Mann-Whitney and chi-square tests were used for group comparisons of continuous and categorical data, respectively. Descriptive continuous data are presented as median and interquartile range (IQR) while categorical variables are listed as numbers and percentages unless otherwise stated. Statistical analyses were performed using SPSS .To deal with the repeated measurements we primarily used Generalized Estimation Equations (GEE) with a binary logistic link for both univariable and multivariable analysis. The association between blips and HIV RNA measurement in the range between 20 and 50 copies/mL, sometimes referred to as low-level viremia was evaluated by stratifying the subjects for the number of samples below 50 copies/ml and then randomly shuffling the blip indicator within each strata to achieve an empirical distribution from which the significance could be obtained. A similar procedure was used to evaluate the association between failure and blips.In total, 4449 blood samples from 735 HIV-1-infected individuals were included    Fig. .Fig. 3Prp < 0.0001). Twenty-seven patients developed viral failure, 55.6 % due to consecutive samples > 50 copies/mL more then 6 weeks apart and 44.6 % due to a single HIV RNA > 500 copies/mL. The median HIV RNA among the last group was 1740 (range 662–12900) copies/mL. A significant correlation was observed between viral failure and viral blips (p = 0.005). The 27 patients with HIV RNA > 500 copies/mL or 2 consecutive samples 50–500 copies/mL did not have a significant higher baseline viral load. Twenty-six of the 27 patients with viral failure were subsequently re-suppressed, in 77 % without treatment alteration. One patient was lost to follow-up after leaving the country.Among the 659 patients who were suppressed during the entire study period, 481 patients (73 %) had a continuous viral load under the detection threshold (HIV RNA <40/20 copies/mL depending on assay version) after the initial six months. Two hundred and thirty-four patients  had at least one plasma HIV RNA measurement between 20 and 50 copies/mL. A significantly larger percentage of these samples were found in the group with viral blips, 111 out of 603 (18.4 %), compared with 255 out of 3453 (7.4 %) samples collected from suppressed patients (p < 0.0001).As expected, subjects with transient plasma viremia had been sampled more frequently, in median nine times compared with five times in suppressed subjects (p = 0.0001).Transient viremia with HIV RNA between 50 and 500 copies/mL was seen in 90 out of 4449 samples (2.0 %). There was a significant difference in blip incidence when comparing different years after ART initiation, with the highest incidence during the second year of observation Fig. . There wThere was no significant difference between subjects with and without blips with respect to sex, AIDS-defining diagnoses, co-infection with hepatitis B and/or C viruses, number of primary drug resistance-associated mutations or where they were treated.Fifty-one per cent of the whole study population was on a regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 42 % on a regimen containing a ritonavir-boosted protease inhibitor (PI/r) (Table p = 0.007 in the logistic model). The same pattern was seen in patients with viral failure where the use of PI/r was significantly more common (p = 0.001).The percentage of patients with blips on a PI/r-based regimen was significantly higher than for subjects on a NNRTI-based regimen, 2.8 % and 1.4 %, respectively , Abbot Realtime HIV-1, and COBAS Ampliprep/COBAS TaqMan HIV-1 v 2.0 (Roche) assays), only 19 % of the detected viral blips could be reproduced with any of the other methods .We found an incidence of viral blips of 10 % in our Swedish cohort. Older studies have found an incidence of 33–40 % using assays with higher quantification limits , 14. In 10 copies/mL) than in suppressed patients (4.55 log10 copies/mL). This is in accordance with findings obtained by older quantification assays [Baseline VL was significantly higher in subjects with blips  in accordance with another study [One of the most important questions is whether there are any consequences of viral blips, particularly development of subsequent viral failure. We found a significant association between viral blips and viral failure . In the multivariat analysis the strong correlation between viral blips and year on treatment is caused by calendar year, which was unexpected. A prior study demonstrated that switching from COBAS TaqMan v1.0 to v2.0, as was the case in this study, resulted in a increased number of detected HIV RNA levels that the researchers concluded was the result of increased sensitivity due to reduced underquantification . UpgradiThe Swedish national HIV-cohort has a low incidence of viral blips (10 %). Blips were associated with high baseline viral load and an increased risk of subsequent virological failure. More data is needed to determine the clinical relevance of this phenomenon and further studies would benefit from harmonised definitions.AIDS, acquired immune deficiency syndrome; cART, combination antiretroviral therapy; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; VL, viral load


Anaemia is associated with adverse outcomes including early death in the first year of antiretroviral therapy (ART). This study reports on the factors associated with persistent anaemia among HIV-infected patients initiating ART in the Democratic Republic of Congo (DR Congo).We conducted a retrospective cohort study and analyzed data from patients receiving HIV care between January 2004 and December 2012 at two major hospitals in Goma, DR Congo. Haemoglobin concentrations of all patients on ART regimen were obtained prior to and within one year of ART initiation. A logistic regression model was used to identify the predictors of persistent anaemia after 12 months of ART.Of 756 patients, 69% of patients were anaemic (IC95%: 65.7–72.3) at baseline. After 12 months of follow up, there was a 1.2 g/dl average increase of haemoglobin concentration (P < 0.001) with differences depending on the therapeutic regimen. Patients who received zidovudine (AZT) gained less than those who did not receive AZT . Among 445 patient who had anaemia at the beginning, 33% (147/445) had the condition resolved. Among patients with anaemia at ART initiation, those who did not receive cotrimoxazole prophylaxis before starting ART and a AZT initial regimen  were significantly at risk of persistent anaemia.More than two thirds of patients had anaemia at baseline. The AZT-containing regimen and absence of cotrimoxazole prophylaxis before starting ART were associated with persistent anaemia 12 months, after initiation of treatment. Considering the large proportion of patients with persistence of anaemia at 12 months, we suggest that it is necessary to conduct a large study to assess anaemia among HIV-infected patients in Goma. Anaemia during infection with the human immunodeficiency virus (HIV) may have multiple causes . The preThe incidence of anaemia increases with the progression of HIV infection –6. AnaemIn addition to reduced physical functioning and quality of life caused by anaemia, its presence at the initiation of ART has been associated with HIV disease progression and mortality , 9–14. IThere has been a decline in the prevalence of anaemia and an increment in mean CD4+ T cell count among HIV infected patients after ART initiation, as seen from studies carried out in Africa, such as Adane’s study . ResearcMortality is higher in the first year of ART, with anaemia being cited as one of the factors of death among patients receiving ART , 15. TheWe conducted a retrospective cohort study on patients from two major hospitals, the Virunga hospital and Goma provincial referral hospital (GPRH) in Goma. This is a city located in the eastern part of DR Congo that has been affected by civil war for many years, and which has a prevalence of HIV of 0.9% . HIV carWe describe the baseline haematological profile in a cohort of treatment-naïve individuals aged 15 years or older. These patients were enrolled in the HIV care and treatment programme at the Virunga hospital and GPRH between January 2004 and December 2012.In DR Congo, including Goma, ART was initiated in accordance with guidelines from the World Health Organization (WHO) and the National AIDS Control Program –20. FirsAnaemia was defined according to the WHO guidelines, as a haemoglobin concentration of <12 g/dl for women and <13 g/dl for men . We clasThe following informations were collected: socio-demographic characteristics , clinical characteristics  and biological characteristics . The outcome, one year after the start of ART was the persistence of anaemia. Loss to follow-up was defined as failure to return to the centre 3 months after the last clinic visit. Mortality was ascertained through family or hospital report as well as, active tracing.All patients who were anaemic at the time of ART initiation and had a follow-up haemoglobin measurement 12 months later were included in the analysis.In general, we applied the value closest to starting ART as the baseline value. Chi-square tests were used to study the association of baseline characteristics with severity of anaemia at baseline. The mean of the haemoglobin concentration and its confidence interval were calculated. Paired samples t-tests were used to compare haemoglobin concentration before and 12 months after ART initiation. Overall changes in haemoglobin concentration on treatment were further examined by stratifying results by sex  at treatment initiation using the t-test. The paired t-test was used to compare the haemoglobin gain over 12 months between the group receiving AZT and those not receiving AZT. McNemar’s test was used to compare the proportion of patients with anaemia at the beginning and end of the first 12 months on ART.A logistic regression model was used to identify predictors of persistent anaemia after 12 months of ART among anaemic patients at treatment initiation. Gender, age, stage of disease, ART regimen, cotrimoxazole prophylaxis and CD4 count at baseline were entered into a logistic model to find the factors associated with the persistence of anaemia. Data were analysed with SPSS version 21.0 for Windows. All tests were two-sided and the level of significance was set at P < 0.05.This study was approved by the institutional review board ethics committee for research subjects at Kinshasa University School of Public Health. Written informed consent was not given by participants for their clinical records to be used in this study, but patient records/information was anonymized and de-identified prior to analysis. (No App: ESP/CE/034/14 of 27.08.2014).A total of 844 HIV patients were enrolled in the HIV program between January 1, 2004, and December 15, 2012. We excluded those who had not yet been on ART for 12 months (79 patients) and those with missing Hb values at enrolment (88 patients). Overall, the excluded patients were similar to those who were kept in the analysis in terms of age (mean 39.51± 9.79 years) and gender  distributions. Among 445 patients who had anaemia at the beginning, 33% (147/445) had resolution of anaemia See .A total of 756 HIV-infected subjects who were eligible for this study and included in this study . The meaOf the 656 patients with documented haemoglobin concentrations at initiation of ART and the end of the first 12 months, 67.3% (445/656) were anaemic at initiation. Twelve months later, the proportion of patients with anaemia was reduced to 43%  (See At ART initiation the mean haemoglobin was 11.06 g/dl (SD 2.06), with women having a lower haemoglobin than men . After receiving ART for 12 months, the mean haemoglobin increased to 12.31 g/dl (SD 1.96) See .Two hundred thirty-two patients who did not have anaemia at the time of ART initiation, and 79 patients who were anaemic at enrolment and received ART for less than 12 months were excluded in the logistic regression model. Among patients who were anaemic at ART initiation, the absence of cotrimoxazole prophylaxis prior to initiating ART  and an AZT-containing initial regimen  were significantly associated with the persistence of anaemia Tables  DatasetsIn this study 69% of HIV-infected subjects had anaemia at the time they had been enrolled in HIV care. Women were more likely than men to be anaemic. Patients who were not on cotrimoxazole prophylaxis before ART initiation and those on an AZT-containing regimen were more likely to have persistent anaemia 12 months after initiation of ART. Among 445 patients with anaemia from the start, 33% had resolution of anaemia.Haemoglobin concentration increased significantly in patients who received ART; on average the haemoglobin increased 1.2 g/dl over the first 12 months. European and North American studies reported that ART is associated with resolution of HIV-associated anaemia , 17. MorAlthough we observed an increase in haemoglobin over the 12 months follow up, differentials exist depending on the ART regimen, patients on AZT-based regimen experiencing a lower increase in haemoglobin compared to those on D4T-based regimen. Similar findings were reported from Uganda where anaemic patients on D4T- containing regimens had a significantly larger increase in haemoglobin than those on AZT-based regimens . The samWe also found that persistent anaemia was associated with ART regimen and chemoprophylaxis of cotrimoxazole. Patients who had an initial AZT-containing regimen were more likely to have persistent anaemia, which is in line with a previous cohort study in a rural hospital in Tanzania showing that the majority of patients who were anaemic at the time of ART initiation had significantly increased haemoglobin levels over the initial 12 months of ART. However, patients on AZT-based regimens had more risk of persistent anaemia . There iOur results also support findings that ART improves haemoglobin regardless of the regimen type (AZT containing versus non-AZT containing) and the degree of immuno-suppression; however, correction of anaemia does not have the same magnitude depending on the therapeutic regimen received by the patient (AZT-based vs non- AZT-based). These results underscore the possible caveats of AZT, and suggest that other drugs might be preferable in anaemic patients, especially in countries such as DR Congo where anaemia is endemic, and probably related to malaria, intestinal parasites, malnutrition and other causes. The 2013 revision of the WHO guidelines recommended tenofovir (TDF) in combination with 3TC or FTC and a non-nucleoside reverse transcriptase inhibitor as the first regimen option in individuals initiating ART unless contraindicated .An unexpected finding was the negative association between the prescription of cotrimoxazole and anaemia. Its use is known to be associated with aplastic anaemia or immune-mediated destruction of specific populations of blood cells ; but ourRegarding several limitations in the present study, the first is related to the technique used to collect data. Indeed, with the review of patient records, some information may have been recorded with little rigor or accuracy. Second, we did not take into account other factors such as adherence to treatment, transfusion history and the presence of co-morbidities . Nevertheless, this study has the advantage of being among the few to document factors associated with persistent anaemia during the first year of ART not only in the DR Congo but in an area with ongoing conflict for several years.Over two-thirds of patients had anaemia at baseline. An AZT-containing regimen and absence of cotrimoxazole prophylaxis before starting ART were associated with persistent anaemia 12 months after initiation of treatment. Considering the large proportion of patients with persistence of anaemia at 12 months, we suggest that it is necessary to conduct a large study to assess the anaemia among HIV-infected patients in Goma.S1 Dataset(XLS)Click here for additional data file.S2 Dataset(DTA)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Due to discontinuation of the Siemens Versant HIV-1 RNA (bDNA) assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV-1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut-off of 20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory demonstrated previously that a significant proportion (18%) of patients undetectable using bDNA HIV-1 RNA quantification exhibited low level viraemia (LLV) using the new assay. Local guidelines recommend that patients stable on therapy receive twice-yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service.A retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed by ≥ one low-level (<400 copies/mL) VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC) were recorded. Patients were identified using laboratory data and information collected from electronic patient records. Results were analyzed with SPSS v18.One hundred and ninety patients were included. Demographics: 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current treatment regimens were 43.3% PI-based; 43.3% NNRTI-based and 13.7% other. Patients were stratified into VL 20–49 copies/mL (n=109); VL 50–199 copies/mL (n=71) and VL 200–399 copies/mL (n=10). In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV-1 genotype requests and 16 VC discussions . Longer Changes in assay can result in difficulties in interpretation of patient results. The assay switch in our service had significant impact on patient and staff time and cost with an increase in patient recalls; increased frequency of VL measurement, genotypes and discussions in VC. Choice of assay is paramount to running an efficient and cost-effective clinical service.