BackgroundSwitch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90′ of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005.MethodsRetrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of ≥50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients.ResultsThe cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs ≤ 5000 copies/ml, patients with VLs = 5001–10,000 copies/ml had an aHR = 1.81 (95% CI = 0.9–3.6), and patients with VLs > 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9–6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 ≥ 100 cells/ul (aHR = 2.30, 95% CI = 1.5–3.6). Mortality in patients not switched to second-line ART was 11.9%, compared to 1.2% for those who switched (p = 0.009). Patients switched after 12 months of of virologic failure were more likely to experience CD4 decline and/or further VL increases.ConclusionsIntervention strategies that aid clinicians to promptly switch patients to second-line ART as soon as virologic failure on 1st line ART is confirmed should be prioritized.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2680-6) contains supplementary material, which is available to authorized users.

Virally suppressed Ugandans had a 3-fold lower frequency of rCD4 cells latently infected with replication-competent HIV-1, compared with previous observations in a cohort of American patients, also treated with ART during chronic infection. The biological mechanism driving the observed smaller reservoir in Ugandans is of interest and may be of significance to HIV-1 eradication efforts.

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BackgroundProgrammatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates.Methods and FindingsWe developed a predictive model, the Incidence Patterns Model (IPM), representing populations according to factors that have been demonstrated to be strongly associated with HIV acquisition risk: gender, marital/sexual activity status, geographic location, “key populations” based on risk behaviours (sex work, injecting drug use, and male-to-male sex), HIV and ART status within married or cohabiting unions, and circumcision status. The IPM estimates the distribution of new infections acquired by group based on these factors within a Bayesian framework accounting for regional prior information on demographic and epidemiological characteristics from trials or observational studies. We validated and trained the model against direct observations of HIV incidence by group in seven rounds of cohort data from four studies (“sites”) conducted in Manicaland, Zimbabwe; Rakai, Uganda; Karonga, Malawi; and Kisesa, Tanzania. The IPM performed well, with the projections’ credible intervals for the proportion of new infections per group overlapping the data’s confidence intervals for all groups in all rounds of data. In terms of geographical distribution, the projections’ credible intervals overlapped the confidence intervals for four out of seven rounds, which were used as proxies for administrative divisions in a country. We assessed model performance after internal training (within one site) and external training (between sites) by comparing mean posterior log-likelihoods and used the best model to estimate the distribution of HIV incidence in six countries (Gabon, Kenya, Malawi, Rwanda, Swaziland, and Zambia) in the region. We subsequently inferred the potential contribution of each group to transmission using a simple model that builds on the results from the IPM and makes further assumptions about sexual mixing patterns and transmission rates. In all countries except Swaziland, individuals in unions were the single group contributing to the largest proportion of new infections acquired (39%–77%), followed by never married women and men. Female sex workers accounted for a large proportion of new infections (5%–16%) compared to their population size. Individuals in unions were also the single largest contributor to the proportion of infections transmitted (35%–62%), followed by key populations and previously married men and women. Swaziland exhibited different incidence patterns, with never married men and women accounting for over 65% of new infections acquired and also contributing to a large proportion of infections transmitted (up to 56%). Between- and within-country variations indicated different incidence patterns in specific settings.ConclusionsIt is possible to reliably predict the distribution of ...

Heterosexual intercourse accounts for 80% of HIV transmission in sub-Saharan Africa. Factors facilitating cross-infection may include sexual practices such as the vaginal use of herbs/substances to dry, contract and heat the vagina for enhancement of sexual pleasure. The behavioural-analytic study investigated the use of different types of herbs/substances used by 75 HIV positive and 76 negative sexually active females and the perceived effects of these agents. Individual in-depth interviews were conducted. 99% of all subjects admitted using herbs/substances mainly to contract (94%), dry (58%) and heat (28%) the vagina. There was no significant difference in the pattern of use of herbs and reasons given for using the agents by HIV positive and negative women. 69% of HIV negative and 80% of positive subjects had used a mean of 4 difference types of herbs and/or substances during the last 5 years. 39% negative and 25% positive subjects had experienced intra-vaginal pain and lower abdominal pains during and after sexual intercourse, laceration of the vagina and excessive vaginal secretions after using herbs. These effects were attributed to Wankie (herb or substance) in 70% of the complaints. 14 HIV positive subjects compared with 7 in the negative group had used Wankie. The role of Wankie and similar substances in transmitting HIV cross-infection requires further investigations. From the point of view of AIDS prevention, expectations of a dry and contracted vagina in sexual intercourse may reduce acceptability and use of female and male condoms.