Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

Background. The therapeutic goal of antiretroviral therapy (ART) is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral  suppression. Such discordant immune responses have been associated with poor clinical outcomes.Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation.Methods. Data were analysed from 810 HIV-infected adults initiated on first-line HAART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs) to determine associations between discordant immune response and clinical and demographic factors.Results. At ART initiation, 65% (n=592) of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm3, 70% (n=645) of patients had a haemoglobin level >11 g/dl and 88% (n=803) were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP). Six months after ART initiation, 24% (n=220) of patients had a discordant immune response and 7% (n=67) a discordant virological response. On multivariate analysis, baseline CD cell count .200 cells/mm3 (AOR 3.02; 95% confidence interval (CI) 2.08 - 4.38; p<0.001) and moderate anaemia (8.0 - 9.4 g/dl) atbaseline (AOR 2.30; 95% CI 1.25 - 4.59; p=0.007) were independently associated with the development of discordant immune response, after adjustment for education level, World Health Organization (WHO) clinical stage and ART regimen.Conclusions. Discordant immune response following ART initiation was common and associated with baseline anaemia and CD4 cell count in our cohort. Intensive monitoring of at-risk individuals may improve clinical outcomes

Time to strengthen HIV treatment and prevention for youth

In The Lancet HIV, Mhairi Maskew and colleagues use data from a large national laboratory database in South Africa to examine trends in access to public sector HIV treatment programmes by children and adolescents aged 1–19 years between 2005 and 2016. The authors should be congratulated for highlighting important findings using national data in this often under-examined population, information that is needed to mount a national response. The authors report a ten times increase in the number of adolescents with viral load data, suggestive of antiretroviral therapy (ART) use, between 2005–08 and 2013–16. Prevention of mother-to-child transmission has worked remarkably well, with patients starting ART steadily decreasing since 2011 among patients aged 1–14 years. However, in line with global trends, the authors also identified large gaps in ART initiation among adolescents with presumed horizontal infection; less than half of patients seeking care aged 15–19 years started ART

A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa

In cross-sectional studies increased vaginal bacterial diversity has been associated with vaginal inflammation which can be detrimental for health. We describe longitudinal changes at 5 visits over 8 weeks in vaginal microbiota and immune mediators in African women. Women (N = 40) with a normal Nugent score at all visits had a stable lactobacilli dominated microbiota with prevailing Lactobacillus iners. Presence of prostate-specific antigen (proxy for recent sex) and being amenorrhoeic (due to progestin-injectable use), but not recent vaginal cleansing, were significantly associated with microbiota diversity and inflammation (controlled for menstrual cycle and other confounders). Women (N = 40) with incident bacterial vaginosis (Nugent 7-10) had significantly lower concentrations of lactobacilli and higher concentrations of Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia, at the incident visit and when concentrations of proinflammatory cytokines (IL-1β, IL-12p70) were increased and IP-10 and elafin were decreased. A higher 'composite-qPCR vaginal-health-score' was directly associated with decreased concentrations of proinflammatory cytokines (IL-1α, IL-8, IL-12(p70)) and increased IP-10. This longitudinal study confirms the inflammatory nature of vaginal dysbiosis and its association with recent vaginal sex and progestin-injectable use. A potential role for proinflammatory mediators and IP-10 in combination with the vaginal-health-score as predictive biomarkers for vaginal dysbiosis merits further investigation

Men’s perspectives on the impact of female-directed cash transfers on gender relations: Findings from the HPTN 068 qualitative study

Background HIV is an inherently gendered disease in eastern and southern Africa, not only because more women than men are infected, but also because socially constructed gender norms work to increase women’s HIV-infection risk. The provision of cash transfers to young women alone in such a context adds another dimension to already existing complex social relations where patriarchal values are entrenched, gender inequality is the norm, and violence against women and girls is pervasive. It raises concerns about complicating young women’s relationships with their male partners or possibly even setting them up for more violence. In our attempt to understand how cash transfers influence social relations in the context of a trial among young women in South Africa, we used qualitative data collected during the trial to explore men’s perceptions of the impact of cash transfers on male-female relationships, both intimate and platonic, peer relationships. Method Between April 2012 and August 2015, we conducted focus group discussions (n = 12) and interviews (n = 20) with the male peers and intimate partners of young women aged 13–20 years, who were participating in a phase III randomised controlled trial of CTs for HIV prevention in Mpumalanga, South Africa. A thematic content analysis approach was used to analyse the data. The codebook was developed on the basis of the topic guides, with additional codes added inductively as they emerged from the data. Results Intimate partners were older (range 20–32 years) and more likely to be working than the male peers. Both intimate partners and male peers were supportive of the CT trial targeting young women; younger peers however expressed some concerns that the money might diminish their power and status in relationships. HIV testing requirements associated with the trial appeared to have improved communication about sex and HIV in intimate relationships, with some women even encouraging their partners to go for an HIV test. Conclusion CTs provide AGYW with a measure of autonomy and power to contribute in their gendered relationships, albeit in limited ways. However, there is potential for CTs to have a negative impact on male-female relationships if the cash received by AGYW is equal to or greater than the income earned by their male counterparts or sexual partners

Intimate partner violence and oral HIV pre-exposure prophylaxis adherence among young African women

Objective: To estimate the effect of intimate partner violence (IPV) on oral pre-exposure prophylaxis (PrEP) adherence among adolescent girls and young women (AGYW). Design: We conducted a secondary analysis of data from HIV Prevention Trials Network 082 (HPTN 082), a multisite prospective study designed to assess oral PrEP adherence among AGYW in southern Africa. Methods: We estimated the relative prevalence of high PrEP adherence 3 and 6 months after initiation among AGYW 16 – 25 years who reported a history of any IPV in the past year at enrollment versus AGYW who did not, both overall and by age. High adherence was defined as an intracellular tenofovir-diphosphate concentration at least 700 fmol/ punch or more dried blood spots. Results: Among 409 PrEP-initiating AGYW, half (49%) reported experiencing any IPV by a current/recent partner in the year prior to enrollment. Overall, a similar proportion of AGYW who reported IPV had high PrEP adherence at months 3 and 6 as AGYW who did not report IPV. There was, however, evidence of effect modification by age at month 3: among AGYW less than 21 years old, those who reported IPV were less than half as likely to have high adherence [adjusted PR (aPR) = 0.43, 95% confidence interval (CI) 0.22– 0.86]; among AGYW aged 21 years or older, those who reported IPV were more than twice as likely to have high adherence (aPR = 2.21, 95% CI 1.34– 3.66). At month 6, effect estimates within each age stratum were consistent in direction to those at month 3. Conclusion: IPV events may either impede or motivate PrEP adherence among African AGYW, with age appearing to be an important consideration for IPV-related adherence interventions

Preventing HIV Among Young People: Research Priorities for the Future

To review the current state of knowledge on the prevention of sexual transmission of HIV in adolescents and to highlight existing gaps and priority areas for future research