HIV viral load is recommended for monitoring antiretroviral treatment and identifying treatment failure. We assessed the durability of viral suppression after viral load-triggered adherence counseling among patients with HIV viremia 6 months after ART initiation.Observational cohort enrolled in an antiretroviral treatment program in rural Uganda.Participants who underwent routine viral load determination every 24 weeks and had at least 48 weeks of follow-up were included in this analysis. Patients with viral loads >400 copies/ml at 24 weeks of treatment were given additional adherence counseling, and all patients were followed to assess the duration of viral suppression and development of virologic failure.1,841 participants initiating antiretroviral therapy were enrolled in the Rakai Health Sciences Program between June 2005 and June 2011 and were followed with viral load monitoring every 24 weeks. 148 (8%) of patients did not achieve viral suppression at 24 weeks and were given additional adherence counseling. 85 (60%) of these patients had undetectable viral loads at 48 weeks, with a median duration of viral suppression of 240 weeks (IQR 193-288 weeks). Failure to achieve an undetectable viral load at 48 weeks was associated with age <30 years and 24 week viral load >2,000 copies/ml in multivariate logistic regression analysis.The majority of patients with persistent viremia who were provided adherence counseling achieved robust viral suppression for a median 4.6 years. Access to virologic monitoring and adherence counseling is a priority in resource-limited settings. Adherence to antiretroviral therapy (ART) is critical for successful treatment of HIV infection. Consistent ART use leads to viral suppression and dramatically reduced morbidity and mortality ,2. AdditThe best indicator of adherence and response to treatment is the virologic response . Accordi3 or WHO stage IV disease. Initial treatment regimens consisted of two NRTIs (zidovudine or stavudine plus lamivudine) and nevirapine or efavirenz. Participants were seen weekly for the first month and then biweekly for 2 months followed by monthly follow-up appointments with adherence and HIV risk reduction counseling at all visits. HIV-1 viral load testing using the Roche Amplicor 1.5 Monitor assay  was used to monitor all ART clients every 24 weeks. Individualized adherence plans were developed for patients with a viral load >400 copies/μl at 24 weeks by a multi-disciplinary team composed of physicians, clinic officers, and counselors, with interventions including additional adherence counseling in a one-on-one session with clinicians, assignment of a peer treatment supporter, or in-depth psychosocial counseling interventions by specialized staff.Rakai District, located in rural southwestern Uganda, has one of the highest HIV prevalences in Uganda. The Rakai Health Sciences Program (RHSP), funded by the President’s Emergency Plan for AIDS Relief (PEPFAR), has provided free antiretroviral therapy (ART) since June, 2004 through mobile outreach clinics with biweekly visits to 16 regional health clinics. Starting in 2005, viral load monitoring was introduced to follow all patients on ART. Between June 2005 and June 2011, 2,365 ART-naïve adult (age 18 years or more) participants were enrolled in an open cohort and after ART initiation based on a CD4 cell count <250 cells/mmBaseline characteristics were compared among early suppressors, late suppressors, and non-suppressors using chi-square tests for categorical variables and analysis of variance for continuous variables. We assessed predictors of non-suppression by week 48 among n = 142 patients who failed to suppress by week 24 using stepwise logistic regression to estimate odds ratios associated with gender, age, baseline CD4 cell count, baseline WHO stage and 24 week viral load. Stepwise regression entry criterion was set as p = 0.3 and stay criterion was set as p = 0.15. In order to calculate duration of virolgic suppression, we censored subjects at the time of their last available viral load result. All analyses were conducted using SAS version 9.2.The study was approved by the Uganda Virus Research Institute Scientific and Ethics Committee, The Johns Hopkins University IRB and the Uganda National Council for Science and Technology.Between June, 2005 and June, 2011, 2,365 ART-naïve patients were initiated on ART . We inclEarly suppressors, late suppressors, and non-suppressors differed significantly by age, baseline CD4 count, and WHO clinical stage at time of enrollment , with eaThe majority of late suppressors, 71/85 (84%), remained suppressed well beyond 48 weeks, with median sustained suppression of 4.6 years (IQR 3.7–5.5 years). Virologic failure was identified in 193 (10%) patients by 48 weeks of treatment, including 179/1699 (11%) of early suppressors and 14/84 (16%) of late suppressors. There was no significant difference in the median time to virologic failure between these two groups .Viral load monitoring remains a critical component of HIV care, to evaluate treatment efficacy and provide early warnings of resistance and treatment failure . This stOur findings add to evidence supporting the importance of early viral load determination after ART initiation. In addition to allowing for earlier diagnosis of virologic failure , others The current study reinforces the utility of viral load testing to identify patients with persistent viremia who may benefit from further adherence counseling in order to avoid treatment failure. A recent systematic review found that programs employing such viral load-triggered adherence interventions were able to achieve substantial rates of viral suppression or re-suppression, though the percentage of patients achieving suppression varied considerably between studies . A studyThis study’s retrospective design precludes strong causal inferences about the impact of adherence counseling on viral suppression in patients with persistent viremia. Indeed the high rates of initial suppression observed, as well as the success of our targeted adherence interventions, may in part reflect the effects of closely monitoring viral load itself, rather than the added counseling. Nevertheless, given the growing number of studies reporting an association between viral load-triggered adherence counseling and improved rates of subsequent suppression adds plausibility to the benefits of this intervention. Our findings from a large cohort of patients receiving ART support early viral load monitoring and targeted adherence programs in resource-limited settings.


The emergence of HIV-1 drug resistance mutations has mainly been linked to the duration and composition of antiretroviral treatment (ART), as well as the level of adherence. This study reports the incidence and pattern of acquired antiretroviral drug resistance mutations and long-term outcomes of ART in a prospective cohort from Northwest Ethiopia. Two hundred and twenty HIV-1C infected treatment naïve patients were enrolled and 127 were followed-up for up to 38 months on ART. ART initiation and patients’ monitoring was based on the WHO clinical and immunological parameters. HIV viral RNA measurement and drug resistance genotyping were done at baseline (N = 160) and after a median time of 30  months on ART (N = 127). Viral suppression rate (HIV RNA levels ≤ 400 copies/ml) after a median time of 30 months on ART was found to be 88.2% (112/127), which is in the range for HIV drug resistance prevention suggested by WHO. Of those 15 patients with viral load >400 copies/ml, six harboured one or more drug resistant associated mutations in the reverse transcriptase (RT) region. Observed NRTIs resistance associated mutations were the lamivudine-induced mutation M184V (n = 4) and tenofovir associated mutation K65R (n = 1). The NNRTIs resistance associated mutations were K103N (n = 2), V106M, Y181S, Y188L, V90I, K101E and G190A (n = 1 each). Thymidine analogue mutations and major drug resistance mutations in the protease (PR) region were not detected. Most of the patients (13/15) with virologic failure and accumulated drug resistance mutations had not met the WHO clinical and/or immunological failure criteria and continued the failing regimen. The incidence and pattern of acquired antiretroviral drug resistance mutations is lower and less complex than previous reports from sub Saharan Africa countries. Nevertheless, the data suggest the need for virological monitoring and resistance testing for early detection of failure. Moreover, adherence reinforcement will contribute to improving overall treatment outcomes. The rapid scale-up of antiretroviral therapy (ART) in resource-limited countries has dramatically reduced HIV-related mortality and therefore improved quality of life , 2. ContIn Ethiopia increasing prevalence of TDR with time after the roll-out of ART , 19, thePatient’s inclusion and exclusion criteria have already been described . BrieflyPatients were evaluated with a standardized form at enrolment and diagnosed based on the WHO criteria of AIDS-defining conditions as described earlier . The patAs per the routine clinical practice and the protocol of this cohort each patient underwent an adherence counselling before initiation of ART and at their health care visits every three months. Consecutively, self-reported adherence to ART was assessed by asking the last time the patient forgot to take therapy in four weeks time . Then, an estimate of patient's current adherence to antiretroviral therapy  was made. Patients who reported that they had not forgotten a dose the day prior to their visit and never forget doses were categorized as optimal  [+ T cells count only) and at last by a median time of 30 months on ART . Plasma was separated by centrifugation and stored at-40°C utile used.Blood samples was collected in vacutainer tubes containing ethylene diamine tetraacetic acid (EDTA) at baseline, every 6 months  following the manufacturer’s protocols. Immunological failure was defined as failure to achieve a CD4+ T cells gain of at least 50 cells above pre-therapy level or having an absolute CD4+ T cells count of less than 100 cells/mm3 after one year of therapy. HIV viral load was measured at baseline (N = 220) and after a median time of 30 months on ART (N = 127) using Abbott m2000rt Quantitative RealTime HIV-1 assay  with a lower detection limit of 40 copies/ml.Sample collection and preparation, CD4eviously . In briehttp://hivdb.stanford.edu) and the 2014 IAS mutation list [http://www.bioafrica.net). Nucleotide sequences are deposited in National Centre for Biotechnology Information (NCBI), USA GenBank .Although, WHO defines virological failure using viral load cut-offs of >1000 copies/ml based on two consecutive viral load measurement after 3 months with adherence support, there is no standardized reporting of virologic failure since 3 months may not enough for full viral suppression, and since resistance mutations could be detected in samples with VL of as low as 300 copies/mL and not in patients with viral load of >1000 copies/ml. Thus, in this study, virological failure is defined as HIV RNA > 400 copies/mL in single plasma sample and viral load between 40 and 400 copies/ml was defined as low-level viraemia (LLV). HIV genotyping for detection of drug resistance was done at baseline and after a median time of 30 months on ART (N = 127). Viral cDNA was amplified by nested PCR using outer primers yielding a 1757 base pairs (bp) amplicon and subsequently by the inner primers yielding a 1389 bp amplicon covering the entire protease (PR) and partial (76%) reverse transcriptase (RT) enzymes following an in-house protocol. The amplified HIV-1 viral gene was sequenced using BigDye Terminator Cycle Sequencing kit . Genotypic drug resistance mutations were interpreted according to the Stanford University drug resistance database . Differences between viraemic and non-viraemeic groups were tested using the Pearson Chi-square test, the student’s t-test and the Fisher’s exact test, as appropriate. A P-value of less than 0.05 was considered statistically significant.To identify potential risk factors associated with virologic failure, a bivariable and multivariable logistic regression analysis were conducted by the end of 30 months. Variables included were age, sex, baseline CD4The study protocol and design including the consent procedures were approved by the University of Gondar Ethical Review Committee (RPO/55/291/00). Patients were managed following the national guideline. Written informed consent was obtained from all study subjects and documented in Research Office of the University.The baseline characteristics of the patients at enrolment were described earlier . In brie+ T cells counts of > 200 cells/mm3 with virological failure compared with those with a baseline CD4+ T cells count of ≤ 200 cells/mm3. The median HIV RNA level among viremic patients at 30 months was not significantly different among those on NVP and EFV (906 copies/ml (525–42986) versus 2198 copies/ml (1545–23389); P > 0.05).By on treatment analysis , 88% (112/127) of the patients achieved viral suppression with HIV RNA levels ≤ 400 copies/ml of whom 74% (83/112) had undetectable HIV RNA level . The medGenotyping was successfully determined in 8 of the 15 patients with HIV RNA ≥ 400 copies/ml. Amplification failures were due to low viral loads (ranging from 442 to 1886 copies/ml) probably representing virological blips. Accumulation of drug resistance mutations in RT region selected during treatment was observed in 6 of 8 patients . Briefly+ T cells count of the 127 patients at baseline was 194  cells/mm3 and progressively increased over time (+ T cells count increased significantly in the first 12 months period (+183 cells/mm3) exceeding the rate of the following 24 months . The rate of CD4+ T cells recovery was not different among patients who were taking NVP versus EFV based regimen .By the median time of 30 months on ART, 18 out of 127 patients (14.2%) were non-adherent at least once. The main reasons for non-adherence were health related problems (9/18) and drug side effects (5/18). Accordingly, treatment switching was made  at a median time of 61 days after initiation of ART. All the patients were on appropriate ART regimen as per the National ART guideline and were clinically asymptomatic. The median CD4ver time . The rat+ T cells count of < 50 cells/mm3) and baseline HIV RNA of >100,000 copies/ml were not identified as risk factors for virological failure at 30 months. The presence of baseline transmitted drug resistance mutations was not a risk factor for virological failure by the median time of 30 months on ART, either. However, 14 of 21 patients with baseline transmitted drug resistance associated mutations were lost to follow-up and only 7 out of 21 achieved viral suppression. Other demographic predicting factors  were also not significant risk factors for virological failure at 30 months  in the current study is comparable with recent cross-sectional studies from the region , 13, 23 The emergence and accumulation of acquired antiretroviral drug resistance mutations in 6 of 8 patients  reflect Despite the small number of sequences, the spectrum of drug resistance mutations observed in this study was not complex which is consistent with a recent study from Rwanda . However+ T cells/mm3). This could be due to the natural low CD4+ T cells count among Ethiopians [+ T cells count, slow recovery rate of CD4+ T cells among Africans [+ T cells count depletion independent of HIV RNA load [In this prospective cohort, progressive immune restoration was observed over time similar to previous reports , 33–34. hiopians , 36, latAfricans  or may aRNA load , 39.In conclusion, despite the obvious small number of sequences the findings suggest that in resource limited settings ART can sustain virological efficacy for a substantial length of time and also enhance immunological recovery if supplemented with adherence counselling ensuring an optimal adherence level. However, the 12% virological failure and resistance mutations observed in the absence of the WHO clinical and immunological criteria that presently apply to developing countries suggest the need for affordable virological monitoring and targeted drug resistance testing assays in the region.S1 Table10.1186/1471-2334-14-158.Reprinted from BMC Infect Dis. 2014 Mar 22; 14:158. doi: (PDF)Click here for additional data file.


Adherence to HAART was measured with standardized scales and values of viral load. Two groups were defined: adherents and non-adherents. In the latter, a psycho-educational program was implemented and 6 months later measured adherence to HAART. Knowledge about the infection, CD4 T lymphocytes and HIV-ribonucleic acid values were measured before and after this program. The sample was predominantly male (70%), heterosexual (78%), with a mean age of 49 (SD = 12.7) years, and 48% of participants were not adhering to HAART. After the program, non-adherence decreased to 21.6%. Knowledge about the infection increased from 79 to 97%. A significant increase in CD4 T lymphocytes (mean 540–580) and a decrease in viral load (mean 5411–3052) were observed, the latter of statistical significance. This program seems to be feasible and efficient, improving adherence to HAART.Adherence to Highly Active Antiretroviral Therapy (HAART) is the main prognostic factor associated with HIV disease progression and death. The aim was to evaluate the effectiveness of a psycho-educational program to promote adherence to HAART in HIV patients. A longitudinal study ( HIV infection represents a significant cause of illness and death worldwide . The patConsidering these prior results, the purpose of this study was to evaluate the effectiveness of psycho-educational intervention conducted in a Portuguese hospital specializing in infectious diseases, in promoting adherence to HAART of HIV patients who were not drug addicts.n = 102) was selected in a central hospital specializing in treating HIV patients in Portugal during 3 months  . This scIn the original validation study , the priThe Hospital Anxiety and Depression Scale (HADS) , 59, wasA CD4 T lymphocytes count was performed by collecting blood samples before and after implementation of the intervention program. The samples were collected by nurses at the hospital where the study occurred, using sterile vacuum tubes. The samples were analyzed in a specialized laboratory  and the results were validated by a clinical hematologist.Levels of HIV-RNA in the blood were measured before and after implementation of the intervention program by amplification of viral RNA in plasma and by reverse transcriptase polymerase chain reaction (PCR) method in real time. Analyses were performed at the Instituto Ricardo Jorge in Lisbon. It was considered in this study that the patient had suppressed viral load if HIV-RNA values in the blood were less than 50 copies.A multiple-choice questionnaire was developed by the research team to assess the knowledge that patients had in relation to HIV infection. The questionnaire assesses issues like transmission, prevention, and treatment and was administered at baseline and after the psycho-educational intervention.Adherence to HAART was measured through the simplified Scale for Detecting Problems of Adherence to Antiretroviral Therapy (SDPAAT) . This isIn the original validation study, the scale showed good psychometric proprieties, namely related to sensitivity 0.93 (CI95% 0.78–0.99), specificity 0.70 (CI95% 0.51–0.84), and a likelihood ratio of 3.08 (CI95% 1.28–7.39). The validation process for the Portuguese population includes its administration to the sample of the present study, after its independent translation and back-translation process by bilingual Spanish–Portuguese specialists.The different measures were completed by patients. The main outcomes considered were adherence to HAART, proportion of incorrect answers about HIV infection, and values of CD4 and HIV-RNA. These outcomes were reassessed 6 months after the first intervention.n = 49) were submitted to a group intervention program, comprising two sessions, sponsored by a specialist community health nurse. Each patient was called by phone for each session. The sample of non-adherents was divided into three groups with 12 members each and one group with 13. All of them were questioned about their availability at the time of contact. In the case of no response to the first phone call, three further calls were made on different days. Each session lasted 120 min. The sessions were developed in the training room of the hospital on weekdays (Monday to Saturday), alternating between the morning and afternoon in order to maximize the likelihood of patient attendance.Patients classified as non-adherent to HAART .For the validation of SSSS and in order to extract common factors from the interpretation of the items relating to this scale, an exploratory factor analysis was performed (with varimax rotation) to explore the behavior of the scale with this particular population. Cronbach’s alpha was computed to assess the internal consistency of the validated scale and its factors.The validation of SDPAAT was performed by calculating its sensitivity (ratio of non-adherents detected by SDPAAT and the true non-adherents) and specificity (ratio between adherents detected by SDPAAT and the true adherents).Finally, to assess the significance of some variables on the likelihood of adherence to HAART, the logistic regression method Forward: LR –66 was un = 102), 70% of individuals were male and had an average age of 49 (SD = 12.7). Most were unmarried (56%) and almost all were Caucasian (97%). The majority were heterosexual (78%) and 70% had completed secondary education. The most common (35%) professions were in the tertiary sector .In the initial sample , and that their spouse or partner was the best person available to help.Table According to HADS, it was verified that 52.9% suffered from anxiety, ranging in level from mild to severe . In relation to depression, 28.4% scored for depression .Through analysis of Table p < 0.01) with the SSSS total score.Regarding the SSSS factorial analysis, revealed the presence of four components explaining 68.6% of the total variance in this sample of HIV patients, namely Social Activities, which explained 35.1%, Satisfaction with friendships (14.6%), Satisfaction with family (11.9%), and Intimacy (7.1%). All the factors found showed good internal consistency , except for Intimacy (α = 0.42), and all significantly correlated (n = 49) of the total sample (n = 102) was classified as non-adherent. In relation to SSSS dimensions and HADS sub-scales, no significant differences were found in the mean values between the group of adherent and non-adherent, classified by SDPAAT.The present study is part of the validation process of the Portuguese version of SDPAAT, tested in the total sample of 102 patients. The scale showed a sensitivity of 0.61 (CI 95% 0.52–0.71) and a specificity of 0.82 (CI 95% 0.74–0.89), when compared with viral load values, used as gold-standard. Using the SDPAAT scale, 48%  between the first  and final moment    Table .p < 0.01; non-adherents, from 360 to 416, p < 0.05).In both groups, the CD4 lymphocytes significantly increased between the first and second assessments . In fact, most of the individuals who had initially adhered to therapy remained until the end (91%). After the implementation of the psycho-educational program, 65% of the initial non-adherent individuals became adherents to HAART. In all samples, the adherence to HAART after the implementation of the program increased from 52 to 78%.Analyzing the data of Table p = 0.054) and knowledge about infection (p = 0.051) almost reached statistical significance.In the present study, an additional analysis of the impact of some variables described in the literature as predictors of adherence to HAART was carried out. No variables were independently associated with the adherence to HAART, although gender .Some limitations of the present work resulted from the lack of a control group and the study’s experimental design.per se with the health professional, when the assessments were performed. The literature shows that the rates of adherence to intervention programs continue at a lower level in spite of innovative programs (Also it must be taken into consideration that these results may have been influenced by the additional contact programs , 67. In Further studies should be conducted with randomized clinical trials. It is essential that patients know the health professionals and that the co-construction of knowledge is based on empathy that is established between patient and professional. It is important that health professionals assume the commitment to foster targeted interventions with innovative models to promote care , 68–71. Lia Fernandes and Mário Dinis Ribeiro contributed to the conception and design of the work. Clarisse Ribeiro participated in the data collection and in drafting the work, as well as in analysis and interpretation of data, with Rui Sarmento e Castro, Mário Dinis Ribeiro, and Lia Fernandes, who also critically revised the paper. All the authors have approved the final manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.http://www.frontiersin.org/Journal/10.3389/fpsyt.2014.00198/abstractThe Supplementary Material for this article can be found online at Click here for additional data file.


Previous research has raised concerns that patients given nevirapine (NVP)-based regimens experience more virologic failure than patients given efavirenz (EFV)-based regimens. We investigated this hypothesis in a cohort of HIV-positive patients at a large HIV treatment clinic in South Africa.All antiretroviral therapy (ART)-naïve non-pregnant patients, ≥18 years old, without tuberculosis, who initiated treatment with either NVP or EFV from April 2004 to August 2011 at the Themba Lethu Clinic in Johannesburg, South Africa, were included. Log-binomial regression and modified Poisson regression were used to estimate risk ratios (RR) with 95% confidence intervals (CI) for predictors of virologic failure, virologic suppression, and loss to follow-up (LTF), whereas a Cox proportional hazards model was used to estimate the risk of death, all within one year.3 (36–169). Of these patients, 93.2% initiated an EFV-based regimen. After adjusting for baseline characteristics, no difference in death (adjusted Hazards Ratio (aHR): 0.92; 95% CI: 0.68–1.25), LTF (adjusted Risk Ratio (aRR): 1.00; 95% CI: 0.79–1.25), nor suppression  at one year was found between regimens. Among patients with ≥1 viral load ≥4 months after ART initiation, 4% (n=350) experienced virologic failure within 12 months of initiation. Patients initiating NVP-based regimens were 60% more likely to fail than patients initiating EFV-based regimens .Of 12,840 included patients, 62.0% were female and the median baseline CD4 count was 98 cells/mmIn this cohort, patients initiating NVP-based regimens experienced more virologic failure than patients initiating EFV-based regimens. Future guidelines should consider the implications of different efficacy profiles when making recommendations for which drugs to prioritize. The debate over which non-nucleoside reverse transcriptase inhibitor (NNRTI) should be prescribed in combination with antiretroviral therapy (ART) for the treatment of HIV infection has been growing recently. Under current guidelines released in June 2013, the World Health Organization (WHO) recommends efavirenz (EFV) with either lamivudine or emtricitabine and tenofovir for newly initiating adult patients . As NVP Recent studies have indeed begun to fuel these concerns. A recent analysis combining cohorts from across the United States and Europe comparing NVP- to EFV-based regimens reported an increased risk of death and virologic failure among those taking NVP . LikewisAlthough these studies provide some evidence of increased risk of virologic failure associated with NVP, few studies have been conducted to determine if this hypothesis holds in the public sector of resource-limited settings after the rollout of ART. Furthermore, most of these studies are subject to confounding by indication, as patients given NVP may be prescribed this drug for reasons which would be correlated with different overall health status than those prescribed EFV (e.g. pregnancy or a desire to get pregnant). In a recent publication, we examined this hypothesis amongst patients initiating ART with tenofovir and lamivudine and found an increased risk of failure for patients prescribed NVP over EFV . In orde3or a WHO Stage III or IV condition [The study was conducted at the Themba Lethu Clinic in Johannesburg, South Africa. Themba Lethu has been providing outpatient HIV care and treatment since 2004 when it opened as a public-sector clinic with NGO support. Patients are currently treated under the 2013 South African National Treatment guidelines which call for ART initiation at a CD4 count ≤350 cells/mm3 and men with CD4 counts >400 cells/mm3 [Since Themba Lethu began initiating patients onto ART in 2004, more than 30,000 patients have received care and more than 12,000 patients are currently on treatment . Under cAll patient-level data, including information on demographics, medications, laboratory test results, clinical conditions, and other clinical details, are captured at the time of the patient encounter by a physician in an electronic medical record called TherapyEdge-HIV™ . RoutineFor the first six months after initiating treatment patients are seen monthly. Once stable, patients are seen every two months for either a medical visit or for a medication pick up. Deaths are ascertained through passive follow-up and, for the 61% of patients who provide one, by linking national identification numbers with the National Vital Registration Infrastructure Initiative for patients who are LTF . The lin3, men initiating NVP with a baseline CD4 count >400 cells/mm3 and any patient without a baseline CD4 count from the analysis.We included all ART-naïve, adult (≥18 years old) patients who initiated ART between April 2004 and August 2011 at the Themba Lethu Clinic. We excluded patients who were either pregnant or co-infected with tuberculosis at the time of ART initiation as, during the period of this analysis, these patients should have received a specific regimen for cause. We additionally limited our analysis to patients who initiated onto a standard ART regimen under the guidelines. This meant lamivudine with a choice of tenofovir, zidovudine, or stavudine, and either NVP or EFV. Because of the recommendation that patients with high CD4 counts should not be prescribed NVP, we excluded women initiating NVP with a baseline CD4 count >200 cells/mmAs the rollout of ART began in April of 2004, we defined the year of ART initiation in cohort years with each year starting in April and ending in March of the following year. Viral load and CD4 count results are uploaded directly into TherapyEdge-HIV™ from the South African National Health Laboratory Service (NHLS) on a daily basis. Baseline CD4 count was defined as the CD4 count taken closest to the date of ART initiation from six months prior to two weeks after the date of initiation, whereas the values for other baseline variables, namely body mass index (BMI) and Hb, were defined as the value closest to the data of ART initiation from 30 days prior to 7 days after ART initiation.3, 50–99 cells/mm3, 100–199 cells/mm3 and ≥200 cells/mm3. For defining anaemia, Hb was adjusted downward by 0.65 g/dL to account for elevation above sea level in Johannesburg [Baseline CD4 count was categorized as <50 cells/mmnnesburg . AnaemiaDemographic and clinical characteristics at baseline are presented using proportions for categorical variables and medians with corresponding interquartile ranges (IQR) for continuous variables. Our outcomes of interest were virologic failure, virologic suppression, death and LTF, all within 12 months of ART initiation. Virologic failure was defined as two consecutive (between two weeks and six months apart) viral loads >1000 copies/ml at least four months after ART initiation whereas virologic suppression was defined as one viral load <400 copies/ml. LTF was defined as being ≥3 months late for a scheduled visit with no subsequent visit.p<0.2 in univariate analyses were also included. All analyses were conducted using SAS version 9.3 .For each outcome of interest, we present the proportion of the population experiencing the outcome. To determine predictors of virologic failure, virologic suppression, and LTF we used either log-binomial regression or modified Poisson regression with robust error estimation to estimate risk ratios (RR) and present them along with 95% confidence intervals (CI). We also present a Kaplan–Meier curve for the probability of death by drug regimen and hazard ratios for the risk of death from a Cox proportional hazards model. Age, sex, and baseline CD4 count were included in each adjusted model and other potential confounding variables that had a In order to determine whether levels of virologic failure remained elevated for NVP patients using different definitions of failure, we conducted a sensitivity analysis. For this analysis, we defined virologic failure at one year as: 1) two consecutive (between two weeks and six months apart) viral loads >400 copies/ml at least four months after ART initiation, 2) a single viral load >1000 copies/ml at least four months after treatment initiation and 3) either two consecutive failing viral loads >1000 copies/ml (between two weeks and six months apart) or one viral load >1000 copies/ml with no further documentation of suppression.We conducted a second sensitivity analysis to see if the association between NVP and virologic failure remained when allowing for failure ever on treatment. We used our original definition of failure and included all patients with ≥1 viral load after four months on treatment.https://sites.google.com/site/biasanalysis/).In order to show the effect of a potential unmeasured confounder on the association between the initiating NNRTI and virologic failure, we also present the results of a multidimensional bias analysis that adjusts the analysis for such an unmeasured confounder. Each cell represents a measure of association of choice of NNRTI on virologic failure adjusted for the unmeasured confounder using assumptions about the prevalence of the unmeasured confounder among those given NVP and those given EFV, the strength of the association between the unmeasured confounder and virologic failure and standard formulas for correcting the unmeasured confounder , 19. TheThis analysis was approved by the Human Research Ethics Committee  of the University of the Witwatersrand and analysis of anonymized data was approved by the Institutional Review Board of Boston University.Between April 2004 and August 2011, 15,850 adult patients initiated one of the regimens of interest at the Themba Lethu Clinic in Johannesburg, South Africa. We excluded 161 pregnant women, 2286 patients co-infected with tuberculosis, 111 patients initiated on NVP with high CD4 counts and 452 patients without a baseline CD4 count, leaving 12,840 patients in the final cohort for analysis.Of the 12,840 who were included, 878 (6.8%) initiated a NVP-based regimen while 11,962 (93.2%) initiated an EFV-based regimen. Among the 878 who initiated a NVP-based regimen, most also initiated stavudine (82.9%) while the remainder initiated tenofovir (14.4%) and zidovudine (2.7%). Of those 11,962 patients who initiated an EFV-based regimen, a similar pattern was observed .3 (36–169). Although median CD4 counts at ART initiation were nearly identical across regimens , patients initiating EFV-based regimens were slightly older (median: 37.2 vs. 33.0), were more likely to be WHO stage III or IV (46.1% vs. 37.8%) and were somewhat more likely to have moderate or severe anaemia (48.3% vs. 43.3%) than patients who initiated a NVP-based regimen  and the median IQR baseline CD4 count was 98 cells/mm regimen .Of the 12,840 patients included in the analysis, 1061 patients died (8.3%) within the first 12 months on ART, with EFV patients slightly more likely to die than NVP patients (8.4 vs. 6.3%) . PatientAs a patient cannot be considered LTF before three months on treatment, patients with less than three months of follow-up were excluded from the analysis of loss, leaving 12,059 patients in the cohort. LTF was similar across treatment regimens  and no difference in LTF was found after adjusting for baseline characteristics (adjusted Risk Ratio (aRR): 1.00; 95% CI: 0.79–1.25) .n=9212; 92.5%) with little variation between regimens both before  and after adjusting for baseline characteristics   patients had at least one viral load conducted. Among these patients, viral suppression was common (95–1.00) .n=350) experienced virologic failure and 90.6% of those patients failed while on their initiating regimen. However, a higher proportion of patients prescribed NVP experienced failure in the first year on ART compared to patients initiated on an EFV-based regimen (6.7% vs. 3.7%).Virologic failure occurred infrequently in the first year on treatment. Among the 8854 patients with at least one viral load between 4 and 12 months on treatment, only 4.0% . After adjusting for year of ART initiation, sex, age, baseline CD4 count, baseline anaemia and NRTI, a strong association remained and NVP patients were almost 60% more likely to fail than EFV patients  .In order to determine whether or not there was a difference in the association between NNRTI and virologic failure by sex, given possible exposure to single-dose NVP as part of prevention of mother-to-child transmission (PMTCT) programmes, we conducted an analysis stratified by sex. In an unadjusted model, male patients prescribed NVP were 32% more likely to fail compared to EFV patients  whereas female patients prescribed NVP were more than twice as likely to fail as EFV patients . However, when adjusted for year of ART initiation, age, baseline CD4 count, baseline anaemia level and NRTI, the difference between sexes was reduced. The RR of failure comparing NVP to EFV for males was 1.40 (95% CI: 0.77–2.55), whereas for women it was 1.64 (95% CI: 1.08–2.49).n=10,851) and re-classifying patients with missing viral loads as virologic failure  resulted in an adjusted RR of 1.09 (95% CI: 0.98–1.22). Using the final definition of either two failing viral loads or one failing viral load with no further evidence of suppression resulted in an adjusted RR of 1.59 (95% CI: 1.25–2.02).For the first sensitivity analysis, using the first definition of virologic failure requiring two failing viral loads >400 copies/ml, NVP patients were more than 50% more likely to fail  compared to EFV patients, with a similar risk after adjusting for year of ART initiation, age, sex, baseline CD4 count, BMI and NRTI . With the second definition requiring just one single failing viral load >1000 copies/ml, NVP patients were still more likely to fail than EFV patients in both unadjusted  and adjusted models . Requiring that the single failing viral load be conducted while still on the initiating regimen resulted in an adjusted RR of 1.27 (95% CI: 1.07–1.52) and requiring that there also be no evidence of further suppression on the original regimen resulted in an adjusted RR of 1.63 (95% CI: 1.27–2.09). Including only patients with at least six months of follow-up  had at least one viral load ever on treatment (but at least four months after initiation) and were included in the second sensitivity analysis. In this group, 18.5% of NVP patients and 11.6% of EFV patients failed  ever on treatment resulting in an unadjusted RR of 1.60 (95% CI: 1.36–1.89). After adjustment for baseline characteristics, NVP patients were still almost 40% more likely to fail ever on treatment than EFV patients .Most patients in our database were prescribed an EFV-based regimen, as would be expected given the treatment guidelines. The most likely reason for being prescribed NVP is pregnancy or a desire to get pregnant, conditions that are not likely to be associated with greater illness severity or treatment failure. However, given NVP may be prescribed for a particular cause, it is possible confounding by indication explains some or all of the increased failure associated with NVP. For example, while we excluded patients with tuberculosis or women who were pregnant, it is possible our database was not complete and we did in fact include some of these patients in our analysis. In addition EFV is not recommended for patients with a history of mental illness;  however,We found that in order for the true association between the initiating NNRTI and virologic failure to be null, the prevalence of the potential confounder would have to be very high among NVP patients and very low among EFV patients and have a strong association with virologic failure. For example, if 70% of NVP patients but only 13% of EFV patients had the unmeasured confounder and if the RR for the effect of the confounder on virologic failure was 2.69, adjustment for the confounder would result in no association between NVP use and virologic failure. As a confounder with such prevalence distributions between NVP and EFV that is also uncorrelated with any other variables we adjusted for is unlikely, while we may be overestimating the effect of NVP on virologic failure due to unmeasured confounding, it is unlikely that the true association is null.In this cohort of ART-naïve adult patients, patients prescribed a NVP-based regimen were much more likely to experience virologic failure within the first 12 months on treatment compared to patients initiated onto an EFV-based regimen, even after adjustment for age, sex, baseline anaemia and baseline CD4 count. This relationship was found despite the fact that we attempted to exclude patients who would be prescribed a regimen for reasons related to treatment failure (i.e. those with tuberculosis and those pregnant at ART initiation).et al. in their study of Southern African adults  [et al. also found increased risk of failure on NVP (using a failure cut-off of 1000 copies/ml); however, the effect was less pronounced  [Although studies have found conflicting results, , 21 our 4, 2.02) . A studyOur study has several strengths. First, by removing pregnant women and patients co-infected with tuberculosis, we were able to reduce confounding by indication in this cohort. Second, as laboratory results are uploaded directly from the NHLS, we are able to reduce data entry errors and omissions. Third, as we link patients with South African national identification numbers to the National Vital Registration System, we are able to improve ascertainment of deaths in addition to ongoing passive surveillance.This study, however, should also be viewed in light of several limitations. As we do not collect information on adherence, we were unable to control for its effect on virologic outcomes. Further, as PMTCT services are not provided at Themba Lethu, data on prior exposure to single-dose NVP or other PMTCT regimens is limited and we were unable to control for the effects of those exposures. The OCTANE study did find an increased risk of virologic failure for women previously exposed to single-dose NVP who were prescribed a NVP-based regimen compared to a ritonavir-boosted lopinavir-based regimen . HoweverThis analysis provides additional support to evidence provided in other studies that patients prescribed NVP-based regimens experience more virologic failure than patients prescribed EFV-based regimens. However, additional studies with longer follow-up are needed to determine if this increased risk of failure is common across all NVP-based regimens or if it is confined to specific nucleoside reverse transcriptase inhibitor backbones.


With the widespread use of antiretroviral treatment (ART) in Africa, the risk of drug resistance has increased. The aim of this study was to evaluate levels of HIV-1 resistance among patients with HIV-1 and HIV-1/2 dual infections, treated with ART, at a large HIV clinic in Guinea-Bissau.Patients were selected from the Bissau HIV cohort. All patients had HIV-1 or HIV-1/2 dual infection, a CD4 cell count performed before and 3–12 months after starting ART, and a corresponding available plasma sample. We measured viral load in patients with HIV-1 (n = 63) and HIV-1/2 dual (n = 16) infections a median of 184 days after starting ART (IQR: 126–235 days). In patients with virological failure  and with sufficient plasma available, we performed an HIV-1 genotypic resistance test. Thirty-six patients (46%) had virological failure. The CD4 cell count did not predict treatment failure. Of the 36 patients with virological failure, we performed a resistance test in 15 patients (42%), and nine patients  had resistance mutations. The most common mutation was K103N, which confers high-level resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). No major mutations against protease inhibitors (PI) were found.Our results showed that patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau had a high rate of virological failure and rapid development of NNRTI resistance. It remains to be determined whether a more robust, PI-based treatment regimen might benefit this population more than NNRTIs. Widespread use of antiretroviral treatment (ART) in Africa has increased the risk of drug resistance . FactorsMost patients in Africa initiate ART with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) . AfricanThe West African country, Guinea-Bissau, has the highest HIV-2 prevalence worldwide -9. HIV-2This retrospective, follow-up study accessed data from a clinical HIV cohort at Hospital Nacional Simão Mendes, in Bissau, the capital of Guinea-Bissau .Whenever a CD4 cell count is performed, surplus plasma is stored in a biorepository in Aarhus, Denmark. From this repository, we identified data for adult patients with HIV-1 or HIV-1/2 dual infections that had CD4 cell counts and stored plasma samples acquired before and after 3–12 months of ART. HIV-1/HIV-2 discrimination was performed with a SD Bioline HIV 1/2 3.0 test . All stored plasma from patients with HIV-1/2 dual infections underwent an immunofluorescence discriminatory HIV-test  . When INHIV-1 viral load was measured at the Department of Clinical Microbiology, Aarhus University Hospital, Denmark, with COBAS® AmpliPrep/COBAS® TaqMan® . The lower limit of detection was 20 copies/ml. Virological failure was defined as a viral load >1000 copies/ml .When sufficient plasma was available, we studied HIV-1 genotypic resistance in patients with virological failure by sequencing the protease and reverse transcriptase genes with ViroSeq® 2.0 . Mutations were classified as minor or major according to ART resistance consensus statements from the Stanford HIV RT and Protease Sequence database . SubtypeWe used the Chi-square test for categorical variables to compare characteristics of patients with HIV-1 and HIV-1/2 dual infections, and patients with or without virological failure. We compared continuous variables with the Wilcoxon rank-sum test . The significance level was set at 0.05. Statistical analyses were performed with Stata IC 11.0 .All patients provided voluntary, signed, dated, informed consent, or fingerprints when illiterate, prior to enrolment into the cohort. The ongoing HIV cohort studies were approved by the national ethics committee of Guinea-Bissau (Parecer NCP/No.15/2007).Viral load was measured in stored plasma samples from patients with HIV-1 (n = 63) and HIV-1/2 dual (n = 16) infections, acquired before and 3 to 12 months after : 126–235 days) starting ART  or CD4 cell count . At 3–12 months after starting ART, 36 patients (46%) developed virological failure . Of these, eight (60%) showed resistance to at least one antiretroviral drug: one (7%) patient was resistant to NRTIs, four (27%) to NNRTIs, and four (27%) to both. No patient showed major PI resistance.Twelve patients were taking NNRTIs; of these, seven (58%) were resistant to NNRTIs. The most common NNRTI resistance mutation was K103N 5/12, 42%), which caused high-level resistance against efavirenz and nevirapine. One male patient with NNRTI resistance had not received NNRTI treatment but PI treatment. Among the 15 patients tested for resistance  after a median follow-up of six months. Furthermore, over half of these patients developed resistance - predominantly to NNRTIs. The CD4 cell count was not an effective indicator of treatment failure.In the context of ART rollout, the most important drug resistance mutations in HIV-1 were single amino-acid mutations that conferred high-level resistance to NNRTIs. This finding was not surprising, because first-line ART and strategies for preventing mother-to-child transmission were based on NNRTIs. In this study, over half the patients with NNRTI resistance harbored the K103N mutation; thus, detection of this sentinel mutation may be useful in expanded surveillance activities for estimating the prevalence of NNRTI resistance.Although nine patients developed clinically important mutations to either NRTIs or NNRTIs or both, none had been identified and switched to second-line therapy. The CD4 cell count was a poor predictor of treatment failure, which underscored the need for implementing virological measures.This was the first study on HIV-1 resistance in Guinea-Bissau. Knowledge is scarce about resistance mutations in patients with HIV-1/2 dual infections. Thus, despite the small sample size, our results provided valuable information about this relatively unexplored population. Some patients with HIV-1 infections had been coincidentally treated with a first-line PI-based regimen, because they were assumed initially to be infected with HIV-1/2. This provided the opportunity to examine resistance in the context of a PI-based, rather than an NNRTI-based regimen.Unfortunately, we could not successfully measure resistance in all patients with virological failure, due to the lack of stored plasma or difficulties with the PCR assay for some samples. The latter problem could have been due to poor sample storage in Guinea-Bissau, where electricity is intermittent. Thus, we may have underestimated the proportion of patients with resistance.No baseline resistance tests had been performed; consequently, we could not determine whether the observed resistance was transferred or acquired. The one patient with an NNRTI-resistant virus that did not receive an NNRTI may represent a case of transmitted resistance; however, it also may represent a previous, unrecorded exposure to ART. In Senegal, the prevalence of transmitted drug resistance was 4.16% for NRTIs and 1.04% for PIs . In GuinStudies in low- and middle-income countries have indicated, that after 12 months of ART, 82-91% of patients achieve viral suppression . HoweverA previous survey of acquired resistance showed that, among those experiencing therapy failure, 60-70% had developed drug resistance . We idenThe majority of patients was infected with the CRF02_AG subtype, and a minority harbored subtype A, consistent with previous studies in this region . GeneticIn conclusion, we found a high virological failure rate and rapid development of NNRTI resistance among patients with HIV-1 and HIV-1/2 dual infections in Guinea-Bissau. It remains to be determined whether a more robust PI-based treatment regimen might benefit this population more than NNRTIs. Further studies are warranted on drug resistance in patients with HIV-1/2 dual infections.


Venous thromboembolism is a common postoperative complication following orthopedic surgeries, with morbid and potentially fatal consequences. Perioperative low-molecular-weight heparin (LMWH) therapy can reduce the incidence of venous thromboembolism, but may also increase the risk of bleeding complications. Current literature reflects the need to balance the improved efficacy of early initiating prophylaxis with increased risk of perioperative bleeding. The purpose of this study was to compare the effectiveness and hemorrhage related safety of preoperative versus postoperative LMWH therapy for prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE) in hip fracture patients.We retrospectively evaluated 222 patients who underwent surgical treatment at Peking University People's Hospital between January 2009 and December 2010. Patients were allocated to two groups, receiving either preoperative or postoperative initiation of LMWH therapy for venous thromboembolism prophylaxis. Preoperative anticoagulation therapy was initiated 1–12 days prior to surgery (133 patients), and postoperative anticoagulation therapy was initiated 12 h after completion of surgery (89 patients). The preoperative group was further subdivided into four subgroups according to the time of initiation of therapy: 1–3 days before surgery , 4–6 days before surgery , 7–9 days before surgery , and 10–12 days before surgery . Occurrences of DVT, PE, adverse drug effects, intraoperative and postoperative bleeding were recorded, along with concentrations of preoperative and postoperative hemoglobin and length of hospital stay. The above parameters were compared between groups.P>0.05, Chi-square tests). We identified the incidences of major bleeding, minor bleeding, and intraspinal hematoma after spinal anesthesia, which were 0 %/0 %, 3.76 %/3.37 %, and 0 %/0 %, respectively in preoperative and postoperative anticoagulation groups. There was no significant difference in the incidence of bleeding complications between patients receiving preoperatively initiated LMWH with patients receiving postoperatively initiated LMWH. Spinal anesthesia was administered to 168 patients, with no cases of postoperative intraspinal hematoma.Among recipients of preoperative anticoagulation therapy, two patients developed postoperative PE (1.5 %), one patient developed DVT (0.75 %). In the group receiving postoperative initiation of anticoagulation therapy, one patient each developed PE and DVT . There was no difference in the occurrence of PE and DVT between the two groups (Preoperative anticoagulation therapy with LMWH may not increase intraoperative or postoperative blood loss, or the rate of intraspinal hematoma after spinal anesthesia, but also does not significantly reduce the risk of postoperative DVT or PE, compared to postoperative initiation. Surgical intervention is the most common form of treatment for hip fractures. Surgeries like total hip arthroplasty and hip fracture fixation often lead to postoperative venous thromboembolism (VTE), associated with high mortality rates , 2. For 3etc.) were excluded. As per the ACCP guidelines, all included patients were in the high-risk group for VTE  and AAOS guidelines [“Clinical Practice Guideline on Preventing Venous Thromboembolic Disease in Patients Undergoing Elective Hip and Knee Arthroplasty” (2011)] recommend anticoagulation therapy for DVT prophylaxis for patients undergoing hip or knee arthroplasty or surgical treatment of hip fractures . The ACCP = 0.02), and, contrary to expectation, the incidence of major bleeding events was lower in patients with preoperative rather than postoperative initiation of therapy  [Some researchers have recommended against preoperative initiation of anticoagulation therapy under the assumption that it may increase the rate of postoperative intraspinal hematoma in patients receiving spinal anesthesia. Occurrence of spinal cord edema following spinal anesthesia is quite rare (1:150 000), and the risk of spinal hematoma in women undergoing knee arthroplasty is only 1:3600 , 27. Hul = 0.01) .Our study did not detect any significant differences in the effectiveness of DVT or PE prevention between initiation of LMWH therapy ≥12 h before surgery and ≥12 h after surgery. No cases of postoperative intraspinal hematoma were detected among the 168 study patients who received spinal anesthesia for total hip arthroplasty or hip fracture fixation surgery. Preoperative initiation of anticoagulation therapy did not increase the risk of intraspinal hematoma. Moreover, no significant differences were detected in terms of intraoperative blood loss, postoperative wound drainage, change in hemoglobin concentration after surgery, and change in hematocrit after surgery among subgroups of patients in whom anticoagulation therapy were initiated 1–3 days, 4–6 days, 7–9 days, and 10–12 days before surgery.Our study has several limitations. First, this is a single-centered, retrospective observational study subject to inherent biases including unmeasured confounding, selection, and ascertainment bias. Second, the patients enrolled in the study have different fracture types, femoral neck fractures (Garden III-IV), intertrochanteric fractures (Evans-JensenI-V); it is possible that complex fractures may affect the final result, associated with an increase in operation time and a higher postoperative morbidity. Third, we identified potential DVT cases on the basis of clinical features, e.g. lower extremity swelling, pain, stiffness, superficial venous congestion, and increase in skin temperature, without performing routine angiography or color Doppler ultrasonography in all patients. This may have resulted in failure to detect DVT cases with minimal or no clinical signs , therebyAlthough early initiation of anticoagulation therapy is always regarded as more effective in reducing risk of VTE, and postoperative initiation of anticoagulation therapy is considered safer than preoperative initiation, the above results indicate that preoperative initiation of anticoagulation therapy with LMWH may not increase intraoperative or postoperative risk of bleeding, but also does not significantly reduce the risk of postoperative DVT or PE, compared to postoperative initiation. Our study may provide a reference in choosing the appropriate methods to prevent the perioperative venous thromboembolism, but further studies with more accurate diagnostic methods may pave the way for evidence-based intervention in this regard.


Amongst 4,039 patients starting cART at a median CD4 count of 133 cells/mm3, there were 324 (8%) confirmed deaths, with an event rate of 28.83 (95% CI 25.78–32.15) deaths per 1000-person follow-up years; the commonest established causes were pulmonary TB and gastroenteritis. There were 681 AIDS-defining events (60.60 [56.14–65.33] per 1000 person years) with pulmonary TB and chronic diarrhoea being the most frequent causes. Forty-one NADEs were recorded (3.64 [2.61–4.95] per 1000 person years), of which hepatic and cardiovascular events were most common. Other common events recorded outside these definitions included malaria (746 events) and respiratory tract infections (666 events). Overall 24% of patients were lost-to-follow-up. Alongside expected risk factors, stavudine use was associated with AIDS [adjusted HR of 1.08 (0.90–1.30)] and death (adjusted HR of 1.60 [1.21–2.11]). Whilst frequency of AIDS and deaths in this cohort were similar to those described in other sub-Saharan African cohorts, rates of NADEs were lower and far exceeded by events such as malaria and respiratory tract infections.Combination antiretroviral therapy (cART) has been widely available in Ghana since 2004. The aim of this cohort study was to assess the incidences of death, AIDS-defining events and non-AIDS defining events and associated risk factors amongst patients initiating cART in a large treatment centre. Clinical and laboratory data were extracted from clinic and hospital case notes for patients initiating cART between 2004 and 2010 and clinical events graded according to recognised definitions for AIDS, non-AIDS events (NADE) and death, with additional events not included in such definitions such as malaria also included. The cumulative incidence of events was calculated using Kaplan Meier analysis, and association of risk factors with events by Cox proportional hazards regression. Data were closed for analysis on 31 Combination anti-retroviral therapy (cART) for the long-term management of HIV infection is administered to achieve long-term suppression of virological replication and to maintain CD4 cell counts at a level that reduces the risk of morbidity and mortality. It is encouraging that the effectiveness of cART in developing countries in sub-Saharan Africa has been reported to be similar, and often superior in clinical and immunologic outcomes when compared with those from the developed countries Deaths in the era of cART have largely been due to AIDS-defining clinical events in many such reports from developing countries. But the dynamics of mortality is believed to be changing in industrialised countries with non-AIDS defining clinical events assuming greater importance as causes of death as patients live longer on potent cART Ghana like many other countries in sub-Saharan Africa started cART roll-out in 2004. We have recently published a comparative analysis of the effectiveness and tolerability of nevirapine and efavirenz based cART among a large cohort of Ghanaian HIV-infected patients st December 2011. For this analysis, AIDS-defining events, non-AIDS defining clinical events, immune reconstitution inflammatory syndrome, loss-to-follow up, death and adherence to therapy were defined as follows. An AIDS-defining clinical event was defined as the occurrence of any opportunistic infections or malignancy according the World Health Organisation (WHO) Ethical permission for this study was given by the Committee on Human Research Publications and Ethics of the Kwame Nkrumah University of Science and Technology and the Komfo Anokye Teaching Hospital, Kumasi, Ghana (ref: CHRPE/AP/073/13). Our institutional review board waived the need for a written informed consent since this was a retrospective, observational study and anonymised data were collected from patients' records. The study was conducted at the HIV clinic at the Komfo Anokye Teaching Hospital in Kumasi, Ghana, which provides HIV care to a large rural and urban population across central and northern Ghana. Antiretroviral therapy has been administered to patients meeting eligibility criteria since 2004 as has been previously described The diagnosis of a non-AIDS clinical event was adjudicated by consensus between FSS, BN and RP . The conditions classified under NADEs included cerebrovascular accident (stroke), cerebral/sub-arachnoid hemorrhage, myocardial infarction, coronary artery disease, congestive cardiac failure, end-stage renal disease, renal failure, cirrhosis of the liver, esophageal varices, hepatic failure, hepatic coma, hepatic encephalopathy, intestinal adenocarcinoma/lymphoma, penile carcinoma, small cell lung carcinoma, malignant melanoma, hepatocellular carcinoma, squamous cell carcinoma, and squamous cell carcinoma of the anus as previously described Other medical diagnoses that did not fulfil the criteria for AIDS-defining events or serious NADEs were recorded and presented as “medical co-morbidities on cART”. These included conditions such as malaria, urinary tract infections, new onset diabetes mellitus or hypertension.In the present study immune reconstitution inflammatory syndrome (IRIS) was defined as the paradoxical worsening of a previously treated opportunistic infection 2 or Fisher's exact test. Crude incidence rates of events were calculated in person-years of follow-up with 95% confidence intervals calculated using Normal approximation to the Poisson distribution. Risk factors associated with death and AIDS-defining events were assessed using multivariable Cox proportional hazards regression with factors attaining a significance level of <0.10 in univariate analyses included in the final model. For these survival analyses, the month in which patients started cART was set as month zero and one day of follow-up was added to patients who did not attend any follow-up visits after initiating therapy. Time to events of interest, namely AIDS-defining events, loss-to-follow up or mortality, was calculated by subtracting the date of the event from the date on which the patient was started on cART. Patients were censored at December 31, 2011 if there were no event of interest. Explanatory variables included in survival analyses were selected on the basis of their well-recognised impact on clinical outcomes such as AIDS-defining events, loss-to-follow up and deaths. The cumulative incidence of loss to follow up and deaths were calculated using the Kaplan Meier methodology. For all analysis, a 2-sided p-value <0.05 was set as the level of statistical significance. All data analyses were conducted using SPSS version 19.Parametric and non-parametric methods were used to compare baseline characteristics of continuous data between patients started on either efavirenz, nevirapine or a protease inhibitor-based ART. A 1-way analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare means or medians respectively. Comparisons of dichotomous data were performed using χFour thousand and thirty-nine  patients out of 10,500 (38.5%) patients registered between January 2004 and December 2010 initiated first line therapy. There was a female preponderance in a ratio of 2.1: 1.0 with a median age of patients of 38 years (range of 14–78). As shown in The characteristics of patients enrolled in the clinic for care, proportion initiating cART, their WHO clinical stages, median CD4 counts and vital status for each calendar year from 2004 to 2010 are shown in The median (IQR) CD4 count at baseline of 133 (50–218) increased to 314 (204–429) within 6 months of initiation of cART, p<0.0001. This initial increment was sustained at 12 months with a median (IQR) CD4 at 12 months of 355 (244–487), with further increases during follow up to month 90.3. At the close of data for analysis, 27 (60%) patients who developed IRIS were alive, 6 (13%) patients died and 12 (27%) were lost-to-follow up.There were 45 documented cases of IRIS with an overall incidence rate of 4.00 (2.92–5.36) events/1000 person years under follow up. Tuberculosis-associated IRIS was the commonest and manifested clinically as new pulmonary infiltrations (n = 16), lymphadenitis (n = 2) and pleural effusions (n = 2) over a median of 2 months (range: 2 to 12 months). Others included herpes zoster (n = 13), cerebral toxoplasmosis (n = 9), CMV retinitis (n = 2) and cryptococcal meningitis (n = 1). The median age of patients experiencing IRIS was 38 years, 33 (73%) were females and the median CD4 count at initiation of cART was 73  cells/mm3 with an adjusted HR of 3.62 (95% CI of 2.59–5.07).Although robust CD4 recovery was noted among most patients on cART, there were 407 immunological failures with a crude event rate of 3.62 (3.28–3.99) per 100 person years. The median (range) time to occurrence of immunological failure on first line cART was 24 (12–78) months. Factors significantly associated with the risk of immunological failure on multivariable Cox proportional hazards analysis were male sex with an adjusted HR of 1.85 (95% CI of 1.47–2.33), initiating cART below 40 years of age with an adjusted HR of 1.25 (1.01–1.55) and baseline CD4 strata below 200 cells/mmThere were 41 NADEs with the commonest recorded events being hepatic disorders (n = 20), cardiovascular events (n = 10) and new onset severe renal impairment with eGFR below 30ml/min (n = 6); hepatocellular carcinoma (n = 4) and oesophageal carcinoma (n = 1) were the only non-AIDS defining malignancies. The hepatic disorders noted include liver cirrhosis, hepatitis B transaminitis flares and hepatocellular carcinoma which were all observed in patients with HBsAg sero-positivity. The overall crude NADE incidence rate (95% CI) was 3.64 (2.61–4.95) per 1000 person years as shown in By far, the commonest medical morbidity (not fulfilling AIDS nor NADEs criteria) was from infectious causes of which 2,377 events were documented , with ma2, WHO clinical stages 3 or 4 at baseline and CD4 strata below 200 cells/mm3 at initiation of therapy (Six hundred (600) patients (14.9%) experienced a total of 681 AIDS-defining events during follow up on cART with a crude (95% CI) event rate of 60.60 (56.14–65.33) per 1000 person years of follow up . The med therapy .Of the 600 patients who developed AIDS-defining events on cART, 317 (52.8%) were alive as at time of closure of data but 153 (25.5%) were subsequently lost-to-follow up and 130 (21.7%) died of AIDS. The median (range) duration between the first AIDS-defining diagnosis and death was 0.25 months (0 to 72 months) and that for loss-to-follow up was 4 months (0 to 76 months). Patients who developed an AIDS-defining event and were alive at the time of closure of data for analysis survived for a median of 34 months (range of 0 to 88 months).There were 324 (8.0%) deaths over the 11,263.8 person follow-up years giving a crude (95% CI) event rate of 28.83 (25.78–32.15) deaths per 1000-person follow up years. The median (range) time to death was 2 months (0–66) by Mann Whitney's U-test. 202 (62.3%) deaths occurred within the first 90-days of initiation of therapy, 88 (27.2%) from month 4 to month 12, 16 (4.9%) within the second year, 9 (2.8%) within the third year, 3 (0.9%) within the fourth year and 6 (1.9%) within the fifth year of follow up. The Kaplan Meier estimated cumulative incidence of mortality at 6, 12, 36, and 72 months were 6.8%, 7.9%, 9.0% and 9.8% respectively and of attrition (including 324 deaths and 958 loss-to-follow ups) from the programme were 17.3%, 20.7%, 27.8%, 34.5% and 36.5% respectively.3 with an adjusted HR (95% CI) of 2.39 (1.64–3.49), baseline BMI below 16 kg/m2 with an adjusted HR (95% CI) of 2.60 (1.92–3.53) and starting on an NRTI backbone of d4T plus 3TC with an adjusted HR of 1.60 (1.21–2.11).As shown in In a series of 188 hospital-confirmed deaths, the causes of death are as shown in Overall 35.3%  of patients experienced toxicity during follow up. There were 1,603 documented episodes of cART-related toxicities among patients who started first line cART with an event rate of 14.3 events/100 person-years . As shown in This study is among the largest cohort studies documenting morbidity and mortality in an ART programme in sub-Saharan Africa. The data presented in this paper show that there is a sustained and robust immunological recovery on cART among this cohort of HIV-infected patients. This immune restoration accompanied improvements in morbidity as evidenced the steady decline in the incidence of deaths, losses to follow-up, AIDS-defining and non-AIDS defining clinical events. Attrition from the programme, due mainly to deaths and loss-to-follow up as well as AIDS-defining events, occurred predominantly within the first year of treatment and were predicted by clinical and laboratory indicators of advanced HIV disease at initiation of cART.3 were low and comparable with those from several cohorts from developing countries Several studies from both developed For patients who stayed on cART for more than a year, 407 (10.1%) developed immunological failure according to WHO guidelines but only 135 (3.3%) patients in the cohort were switched to second line therapy. The spectra of clinical events classified as IRIS overlaps closely with those diagnosed as AIDS-defining events which occurred at a frequency of 17%. AIDS-defining events on cART occurred at a median time of 6 months, were predicted by low CD4 cell counts, prior AIDS and low BMI at initiation of therapy and were associated with an increased risk of subsequent attrition from the programme. These show that the occurrence of AIDS-defining events in the proximal phases of cART is an indicator of early treatment failure and is representative of progression of HIV disease which cART may be incapable of halting, even when appropriate treatment for opportunistic infections is concurrently commenced. The implication is that cART should be started much earlier, requiring patients to be diagnosed earlier, as has been suggested by others The crude incidence rates of Non-AIDS-defining events of 3.64/1000 person-years is lower compared to that of cohorts from Botswana Malaria was the leading cause of non-AIDS-defining infectious morbidity on cART and was often treated with artemisinin-based antimalarial therapy. The fact that within this HIV cohort, tuberculosis and malaria were the leading causes of AIDS and non-AIDS infectious morbidity respectively underscores their importance among the most important public health challenges Sub-Saharan Africa is attempting to overcome. Unlike in developed countries where AIDS-related mortality on cART is being superseded by Non-AIDS-related mortality The analyses presented in this study have limitations worth noting. As over 60% of patients presenting to the clinic did not start cART, and many with advanced HIV/AIDS were lost to follow-up, it is likely there were many deaths in this group. Hence the population studied was skewed towards those patients who survived long enough to start cART, who may have had different causes of death to those not starting cART. The trajectories of CD4 over time reflect those of patients who remained on cART and thus are influenced by survivor bias. Furthermore the sources of ascertainment of causes of deaths in a significant proportion of patients were by verbal autopsy by relatives whose accuracy may be limited. In spite of these the specific causes of death could be verified by medical certification in 188 (58%) out of 324 events. Similarly, the classification of AIDS-defining events, IRIS and NADEs were influenced by availability of data and arrived at by consensus between the authors and local experts.In summary, cART is effective over the long-term for a substantial proportion of this Ghanaian cohort of HIV-infected patients. Within the constraints of limited resources as it pertains to the ART programme in Ghana, cART was associated with a sustained and durable immunological recovery in most patients, an improvement in morbidity from HIV-infection and trend towards reduction in mortality over the long-term among patients remaining on therapy and in care.


Selection of resistance mutations on antiretroviral therapy (ART) including darunavir (DRV/r) or atazanavir (ATV/r) has been reported infrequently but mainly in clinical trials where patients were followed very frequently . The aim of this study was to evaluate the rate of resistance at failure and mutational patterns emerging in patients receiving DRV/r or ATV/r based-regimen as first line treatment and followed in standard clinical practice with less clinical visits and viral load measurements (median=2 per year).3. Virological failure was defined as two consecutive viral load=50 copies/mL after previous suppression <50 copies/mL, or failure to achieve <50 copies/mL. Predicted susceptibility was determined using the last ANRS algorithm.We studied 1,518 patients starting their first line antiretroviral therapy and followed during at least two years . The median viral load at baseline was 76,000 copies/mL and the median CD4 cell count 384 cell/mmAmong the 1,518 patients, 193 (12.7%) failed during the two years of follow-up. Among patients failing TVD+DRV/r (n=95), the emerging mutations observed were RT M184V  and Pro V32I . Among patients failing KVX+DRV/r (n=8), the emerging mutations observed were RT M184V  and Pro I47V . Among patients failing TVD+ATV/r (n=86), the emerging mutations observed were RT M184V , Pro N88S  and Pro I50L . Among patients failing KVX+ATV/r (n=4), the emerging mutations observed were RT M184V  and no Pro mutation. Most of patients retained virus predicted to be susceptible to all antiretrovirals (22 virus became resistant to 3TC/FTC and three became resistant to ATV). None of them became resistant to DRV.Among 1,518 patients in routine care who started their first line treatment with DRV/r or ATV/r, very few of them (1.4%) selected resistance mutations at failure with three patients selecting an ATV resistant virus. None of them became resistant to DRV. The less frequent follow-up of patients in routine care compared to clinical trials does not impact the resistance selection rate in patients treated by boosted DRV or ATV based regimen.


Switchi® during February-December, 2013; all had undetectable HIV viral load for ≥3 months prior to switching. Patients with previous failures on antiretroviral therapy (ART) including TDF and/or FTC/3TC, with genotype tests showing resistance to components of Eviplera®, or who had changed the third drug of the ART during the study period were excluded. Changes in lipid profile and cardiovascular risk (CVR), and efficacy and safety at 24 weeks were analyzed.Retrospective, multicentre study of a cohort of asymptomatic HIV-patients who switched from a regimen based on 2 nucleoside reverse transcriptase inhibitors (NRTI)+protease inhibitor (PI)/non nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir boosted PI monotherapy to Eviplera®, 6 stopped it  and 6 have been lost to follow up. Lipid profiles of 283 cases were available at 24 weeks and mean (mg/dL) baseline vs 24 weeks are: total cholesterol , HDL-c , LDL-c , tryglycerides , total cholesterol to HDL-c ratio . CVR decreased . CD4 counts were similar to baseline , and 274 (96.8%) patients maintained viral suppression.Among 305 patients included in the study, 298 were analyzed (7 cases were excluded due to lack of data). Men 81.2%, mean age 44.5 years, 75.8% of HIV sexually transmitted. 233 (78.2%) patients switched from a regimen based on 2 NRTI+NNRTI (90.5% EFV/FTC/TDF). The most frequent reasons for switching were central nervous system (CNS) adverse events (31.0%), convenience (27.6%) and metabolic disorders (23.2%). At this time, 293 patients have reached 24 weeks: 281 (95.9%) have continued Eviplera®, lipid profile and CVR improved while maintaining a good immunovirological control. Most subjects switched to Eviplera® from a regimen based on NNRTI, mainly EFV/FTC/TDF. CNS adverse events, convenience and metabolic disorders were the most frequent reasons for switching.At 24 weeks after switching to Eviplera


The optimal timing and modality of therapeutic intervention during early phases of HIV infection is still debated; in our prospective observational study we evaluated immunological and virological outcome in HIV+ patients treated during acute or recent HIV infection.A total of 25 naïve patients with acute  or recent (documented infection within six months) HIV infection were recruited at the Infectious Diseases Units of the University of Milan and Turin from 2009 to 2014. Patients received treatment with two NRTIs+one NNRTI/bPI, with or without an induction phase with an additional fourth drug  until HIV-RNA undetectability maintained for six months. Blood samples for HIV-RNA, lymphocyte subsets and tropism assessment were obtained at the beginning of the treatment (BL). Patients underwent subsequent six-monthly follow up for clinical outcome, CD4 cell count and HIV-RNA up to 18 months.2 test). Modification or interruption of therapy for tolerability took place in 4 out of 25 patients, all while receiving four drugs; two patients underwent STI between 12 and 18 months following virological success.Median increase in CD4 cells from 0 to 12 months was greater in patients treated during acute (n=18) versus recent (n=7) infection . This higher value was maintained through 18 months, although failing to reach statistical significance. Patients with acute or recent infection did not significantly differ in virological success (83.3% versus 85.7% at 12 months). We considered CD4 cells gains at six months (multivariate analysis, ANCOVA; Treatment of primary infection appeared to be effective in preserving the pool of CD4 cells in acute more than recent infection. There was no evidence of a different outcome through the addition of a fourth drug to the standard treatment.


HIV-2 infection is endemic in West Africa and some European countries, namely Portugal. HIV-2 antiretroviral (ARV) treatment presents some restrains related to intrinsic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) and fusion inhibitors, and poorer response to protease inhibitors (PI).Retrospective observational study of a cohort of 135 infected HIV-2 patients, diagnosed between 1989 and 2008.Evaluation of epidemiologic, clinical, immunologic and virologic progression, comparing to groups of patients (naïve vs ARV experienced); characterization of therapeutic, immunologic and virologic response. SPSS version 20.0 was used for statistical analysis.3 at diagnosis (p<0.001). Immunological evolution showed no significant decline in naïve population (Δ=−67 cell/mm3 – p=0.18) and a significant recovery in ARV experienced (Δ=+207 cell/mm3 – p<0.001). Global mortality rate found was 18% (6% vs 13% – p=0.122). Eighty patients initiated ARV: 84% presented a time interval of ARV exposure between 0–5 years (42%) and 5–10 years (42%). Fifty percent experienced ≤2 ARV regimens and the remaining >2 regimes. Considering the first ARV therapy: 56% initiated PI, 30% NTRI and 5% integrase inhibitor (II)-based regimens. Currently, 54 patients maintain regular follow-up and ARV therapy: 60% NTRI+PI; 37% NRTI+PI+II and 3% NRTI+II. TDF/FTC is the backbone in 56%. Most frequent PIs are LPV/r (54%), DRV/r (19%) and ATV/r (12%). Mean time of exposure to NRTI=3 years, PI=7 years and II=2 years. Immunologic recovery was sustained for each of the ARV class considered .The study included 135 patients: 41% (n=55) naïve and 59% (n=80) with ARV experience. The comparison between groups (naïve vs ARV) revealed: male prevalence 76% vs 50%; mean age 54.5 years vs 54.8 (p=0.90); main geographic origin Guiné Bissau (47% vs 44%) and Portugal (22% vs 33%); and transmission mainly acquired by heterosexual contact (87% vs 80%). Mean time since diagnosis was 14 vs 13 years (p=0.31); 2% vs 50% presented AIDS criteria at diagnosis (p<0.001) and 93% vs 38% registered TCD4>350 cell/mm3) and virologic control in 74%. Immunologic behaviour evidenced a sustained gain for each of the ARV class considered.This is a cohort accompanied for a long period and the majority of patients present extensive ARV experience. The ARV-experienced patients registered a favourable response to treatment, with sustained immune recovery (Δ=+207 cell/mm


Among people living with HIV/AIDS, illicit drug use is a risk for sub-optimal treatment outcomes. However, few studies have examined the relative contributions of different patterns of drug use on adherence to antiretroviral therapy (ART). We sought to estimate the effect of different types of illicit drug use on adherence in a setting of universal free HIV/AIDS treatment and care.Using data from ongoing prospective cohorts of HIV-positive illicit drug users linked to comprehensive pharmacy dispensation records in Vancouver, Canada, we examined factors associated with ≥95% prescription refill adherence using generalized estimating equations (GEE) logistic regression.Between 1996 and 2013, 692 ART-exposed individuals were followed for a median of 42.7 months (Interquartile Range: 29.1–71.7). In multivariable GEE analyses, heroin injection  as well as cocaine injection  were associated with lower likelihoods of optimal adherence. Methadone maintenance therapy  was associated with a greater likelihood of adherence.Periods of heroin and cocaine injection appeared to have the most deleterious impact upon antiretroviral adherence. The findings point to the need for improved access to treatment for heroin use disorder, particularly methadone, and highlight the need to identify strategies to support ART adherence among cocaine injectors. The development of antiretroviral therapy (ART) has led to substantial declines in HIV/AIDS-associated morbidity and mortality among many groups in many settings worldwide . AdherenIn many studies, active illicit drug use among individuals living with HIV/AIDS is associated with decreased access to HIV treatment, reduced medication adherence and increased mortality . AlthougData for these analyses were derived from the Vancouver Injection Drug Users Study (VIDUS) and AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), two ongoing prospective observational cohorts of illicit drug users in Vancouver, Canada. Beginning in 1996, persons who had injected illicit drugs other than cannabinoids in the previous month were recruited into VIDUS. Since 2005, persons who used illicit drugs and were HIV-seropositive at baseline or during the study are subsequently followed in ACCESS. Both cohorts use identical recruitment and follow-up procedures to allow for combined analyses.Described in detail previously -10, the The present analyses considered all HIV-seropositive participants who had been dispensed at least one day of antiretroviral therapy (ART) between May 1996 and May 2013. The primary outcome of interest in this study was adherence to ART in the six month period prior to each study interview. As in previous studies , we estiExplanatory variables of interest included socio-demographic data: age (per 10 years older), gender , and Caucasian ancestry (yes vs. no). Variables related to drug use characteristics included: heroin injection (yes vs. no), cocaine injection (yes vs. no), amphetamine injection , crack cocaine smoking (yes vs. no), and enrollment in methadone maintenance therapy (yes vs. no). All drug use characteristics defined above were treated as time-updated based on questionnaire data pertaining to the six month period prior to each study interview ,13. We aAs a first step, we visually inspected trends in the proportion of all participants reporting heroin injecting, cocaine injecting, crack smoking and amphetamine injecting at each interview period. Next, we visually inspected changes in median adherence rate at each interview period over time.p-values are two-sided.Since serial measures for each subject  were available for many participants, we estimated the relationships between different socio-demographic, drug use and clinical factors and adherence using generalized estimating equations (GEE) with a logit-link function. As a first step, we conducted bivariable GEE analyses to determine which variables were statistically associated with adherence in unadjusted analyses. To adjust for potential confounding and identify factors that were associated with the outcome, all significant variables in the bivariable analyses were considered in the full multivariable model. With the drug use patterns being forced into the model, a backwards model selection procedure was used to identify the multivariate model with the best overall fit as indicated by the lowest quasilikelihood under the independence model criterion value. All statistical analyses were performed using the SAS software version 9.3 . All During the study period, 692 individuals were included in these analysis, among whom 213 (30.8%) were female, the median age at baseline was 42 years (Inter-quartile Range (IQR): 35–47) and the median follow-up duration was 42.7 months (IQR: 29.1–71.7). At baseline (Table The bivariable and multivariable GEE analyses of adherence to ART are shown in Table In this long-running community-recruited study of illicit drug users linked to comprehensive HIV clinical records in a setting of universal free HIV/AIDS treatment and care, we observed that periods of heroin and cocaine injection were independently and negatively associated with the likelihood of optimal adherence to ART. We did not observe a statistical relationship between periods of either amphetamine injection or crack cocaine smoking and the likelihood of optimal adherence to ART. Meanwhile, engagement in methadone maintenance therapy was independently and positively associated with optimal adherence to ART.Our finding of strong and independent links between heroin use, engagement in methadone maintenance and the likelihood of optimal ART adherence suggests that the expansion of evidence-based addiction treatment strategies, such as methadone, will likely improve retention in HIV/AIDS care among opioid-dependent illicit drug users -19. ImprIn our study, we did not observe a statistical relationship between amphetamine use and adherence to ART. Crystal methamphetamine use is particularly prevalent among some populations of people living with HIV/AIDS and persons at risk for HIV, especially men who have sex with men. -23 NumerAlthough we observed increasing levels of adherence over time, a substantial proportion of all participants displayed sub-optimal adherence to prescribed treatment at every interview period. Our model indicates that specific drug use patterns each had different relationships to antiretroviral adherence. For example, while periods of heroin injection were 23% less likely to be characterized by ≥95% adherence, there was no significant difference between levels of optimal adherence during periods of amphetamine injection. Unfortunately, our model does not offer specific insights into possible explanations for these divergent results. Thus, future research should investigate the possible behavioural-, psychologic-, social- and structural-level barriers and facilitators of adherence for different groups of illicit drug users in order to optimize substance abuse treatment and support ART adherence.There are some limitations to this study to note. Participant selection for this observational study was not random and the results of this study cannot be generalized to the wider population of HIV-positive illicit drug users. Regarding associations drawn from the results of the study, there is potential for unmeasured confounding. In an attempt to minimize the impact of confounding on the observed relationships we used multivariable modelling. Also, we have previously observed that at least 95% adherence to prescribed ART is strongly associated with viral suppression and survival ,16. NeweTo conclude, our study utilized data from a long-running community-recruited prospective cohort of HIV-seropositive illicit drug users in the setting of free and universal access to HIV care. Periods of injection heroin use and injection cocaine use were both independently and negatively associated with a lower likelihood of optimal adherence to ART while engagement in MMT was associated with higher levels of optimal adherence. Given the importance of addressing substance use in the community and the proven success of MMT at reducing the risk of drug-related harms, our findings support the need to spur efforts to improve access to treatment for problematic substance use among individuals living with HIV/AIDS.