Background We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). Methods The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. Results Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/μL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P < 0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. Conclusion While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals.

OBJECTIVES Since 2006, the British Columbia HIV/AIDS Drug Treatment Program (DTP) has expanded enrollment and dramatically increased its number of participants. We examined the effect this expansion has had on the underlying cause of death in HIV-infected individuals. METHODS We analyzed data from participants aged 18 years and older in the DTP to measure two-year mortality rates and causes of death from 2001–2012. We conducted tests of trend for all-cause and cause-specific mortality, and compared demographics and characteristics of individuals. Cox proportional hazard models were used to determine the risk of death. RESULTS 8,185 participants received ART during the study period. Mortality declined from 3.88 per 100 person-years (PYRs) in 2001–2002 to 2.15 per 100 PYRs in 2011–2012 (p=0.019). We observed significant decreases in HIV-related deaths (2.34 to 0.56 per 100 PYRs; p=0.023) and deaths due to chronic liver disease (0.20 to 0.09 per 100 PYRs; p=0.013), cardiovascular disease (0.24 to 0.05 per 100 PYRs; p=0.026), and suicides (0.47 to 0 per 100 PYRs; p=0.003). Multivariate models, adjusted for age, gender, history of injection drug-use, AIDS diagnoses and baseline CD4 cell counts demonstrated that initiation of ART in all time periods after 2001–02 were independently associated with reduced mortality (p<0.001). CONCLUSIONS We observed declines in HIV-related mortality and certain non-HIV related causes of death among participants in the BC DTP over the study period. These findings suggest that there may be broader benefits to the increasingly liberal HIV treatment guidelines, including reductions in death due to cardiovascular disease and chronic liver disease.

ObjectivesThe current World Health Organization and Uganda Ministry of Health HIV treatment guidelines recommend that asymptomatic patients who have a viral load (VL) ≥ 1000 HIV‐1 RNA copies/mL should receive adherence counselling and repeat VL testing before switching to second‐line therapy. We evaluated the effectiveness of this strategy in a large HIV treatment programme of The AIDS Support Organisation Jinja in Jinja, Uganda.MethodsWe measured the HIV VL at enrolment, and for participants with VL ≥ 1000 copies/mL we informed them of their result, offered enhanced adherence counselling and repeated the VL measurement after 3 months. All blood samples with VL ≥ 1000 copies/mL were sequenced in the polymerase (pol) region, a 1257‐bp fragment spanning the protease and reverse transcriptase genes.ResultsOne thousand and ninety‐one participants were enrolled in the study; 74.7% were female and the median age was 44 years [interquartile range (IQR) 39–50 years]. The median time on antiretroviral therapy (ART) at enrolment was 6.75 years (IQR 5.3–7.6 years) and the median CD4 cell count was 494 cells/μL (IQR 351–691 cells/μL). A total of 113 participants (10.4%) had VLs ≥ 1000 copies/mL and were informed of the VL result and its implications and given adherence counselling. Of these 113 participants, 102 completed 3 months of follow‐up and 93 (91%) still had VLs ≥ 1000 copies/mL. We successfully genotyped HIV for 105 patients (93%) and found that 103 (98%) had at least one mutation: eight (7.6%) had only one mutation, 94 (89.5%) had two mutations and one sample (1%) had three mutations.ConclusionsIn this study, enhanced adherence counselling was not effective in reversing virologically defined treatment failure for patients on long‐term ART who had not previously had a VL test.