Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.

BACKGROUND: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. METHODS: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. FINDINGS: Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3-5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9-5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1-9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39-0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. INTERPRETATION: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. FUNDING: National Research Agency on AIDS and Viral Hepatitis (ANRS)

Internalized HIV Stigma, ART Initiation and HIV-1 RNA Suppression in South Africa: Exploring Avoidant Coping as a Longitudinal Mediator

Introduction: Cross‐sectional evidence suggests that internalized HIV stigma is associated with lower likelihoods of antiretroviral therapy (ART) initiation and HIV‐1 RNA suppression among people living with HIV (PLWH). This study examined these associations with longitudinal data spanning the first nine months following HIV diagnosis and explored whether avoidant coping mediates these associations. Methods: Longitudinal data were collected from 398 South African PLWH recruited from testing centres in 2014 to 2015. Self‐report data, including internalized stigma and avoidant coping (denying and distracting oneself from stressors), were collected one week and three months following HIV diagnosis. ART initiation at six months and HIV‐1 RNA at nine months were extracted from the South Africa National Health Laboratory Service database. Two path analyses were estimated, one testing associations between internalized stigma, avoidant coping and ART initiation, and the other testing associations between internalized stigma, avoidant coping and HIV‐1 RNA suppression. Results: Participants were 36 years old, on average, and 63% identified as female, 18% as Zulu and 65% as Xhosa. The two path models fit the data well (ART initiation outcome: X2(7) = 8.14, p = 0.32; root mean square error of approximation (RMSEA) = 0.02; comparative fit index (CFI) = 0.92; HIV‐1 RNA suppression outcome: X2(7) = 6.58, p = 0.47; RMSEA = 0.00; CFI = 1.00). In both models, internalized stigma one week after diagnosis was associated with avoidant coping at three months, controlling for avoidant coping at one week. In turn, avoidant coping at three months was associated with lower likelihood of ART initiation at six months in the first model and lower likelihood of HIV‐1 RNA suppression at nine months in the second model. Significant indirect effects were observed between internalized stigma with ART non‐initiation and unsuppressed HIV‐1 RNA via the mediator of avoidant coping. Conclusions: Internalized stigma experienced soon after HIV diagnosis predicted lower likelihood of ART initiation and HIV‐1 RNA suppression over the first year following HIV diagnosis. Avoidant coping played a role in these associations, suggesting that PLWH who internalize stigma engage in greater avoidant coping, which in turn worsens medication‐ and health‐related outcomes. Interventions are needed to address internalized stigma and avoidant coping soon after HIV diagnosis to enhance treatment efforts during the first year after HIV diagnosis