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Contains fulltext : 283104.pdf (Publisher’s version ) (Open Access) BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. FUNDING: Unitaid.

Introduction Adolescents and young people comprise a growing proportion of new HIV infections globally, yet current approaches do not effectively engage this group, and adolescent HIV‐related outcomes are the poorest among all age groups. Providing psychosocial interventions incorporating psychological, social, and/or behavioural approaches offer a potential pathway to improve engagement in care and health and behavioural outcomes among adolescents and young people living with HIV (AYPLHIV). Methods A systematic search of all peer‐reviewed papers published between January 2000 and July 2020 was conducted through four electronic databases (Cochrane Library, PsycINFO, PubMed and Scopus). We included randomized controlled trials evaluating psychosocial interventions aimed at improving engagement in care and health and behavioural outcomes of AYPLHIV aged 10 to 24 years. Results and discussion Thirty relevant studies were identified. Studies took place in the United States (n = 18, 60%), sub‐Saharan Africa (Nigeria, South Africa, Uganda, Zambia, Zimbabwe) and Southeast Asia (Thailand). Outcomes of interest included adherence to antiretroviral therapy (ART), ART knowledge, viral load data, sexual risk behaviours, sexual risk knowledge, retention in care and linkage to care. Overall, psychosocial interventions for AYPLHIV showed important, small‐to‐moderate effects on adherence to ART (SMD = 0.3907, 95% CI: 0.1059 to 0.6754, 21 studies, n = 2647) and viral load (SMD = −0.2607, 95% CI −04518 to −0.0696, 12 studies, n = 1566). The psychosocial interventions reviewed did not demonstrate significant impacts on retention in care (n = 8), sexual risk behaviours and knowledge (n = 13), viral suppression (n = 4), undetectable viral load (n = 5) or linkage to care (n = 1) among AYPLHIV. No studies measured transition to adult services. Effective interventions employed various approaches, including digital and lay health worker delivery, which hold promise for scaling interventions in the context of COVID‐19. Conclusions This review highlights the potential of psychosocial interventions in improving health outcomes in AYPLHIV. However, more research needs to be conducted on interventions that can effectively reduce sexual risk behaviours of AYPLHIV, as well as those that can strengthen engagement in care. Further investment is needed to ensure that these interventions are cost‐effective, sustainable and resilient in the face of resource constraints and global challenges such as the COVID‐19 pandemic.

Background: Adjustment to the onset of disability has complex reverberations relating to both socially engendered disadvantage and the realities of functional limitation. Pre-existing ways of understanding disability can meaningfully shape this experience. Objective: This study aimed to provide an exploratory understanding of the experience of becoming disabled in a low-income, under-served, rural South African community. In particular, it was interested in how people with disabilities constructed their struggle within the conceptual split between disadvantage caused by ‘malfunctioning’ bodies (a ‘medical model’ view) and that caused by social organisation (a ‘social model’ view). Methods: Seven people between the ages of 39 and 47 who had acquired a physical disability within the last 4 years were recruited in a rural area of Limpopo province, South Africa. Semi-structured face-to-face interviews were conducted, and the resulting data were thematically analysed. The authors were positioned as both ‘insiders’ and ‘outsiders’ to the participants and sought to use this orientation to best understand and stay faithful to participants’ views while simultaneously applying participant’s experiences to conceptual knowledge in disability studies. Results: Four themes emerged: (1) emotional impact of onset of disability, (2) being introduced to disablist prejudice, (3) being required to take on a ‘disabled’ identity and (4) socio-economic implications of becoming disabled. The findings reflected a complex set of adverse experiences in the lives of the participants, spanning disadvantages based on embodied, cultural, relational and environmental factors, which were superimposed on existing, generalised poverty in their local communities. Participants made sense of their predicament in multiple, evolving ways. Conclusion: This study contributes to the understanding of the complex predicaments, and sense-making, of persons who have acquired a disability in a rural, impoverished Global South environment.

© 2020 World Health Organization; licensed by IAS. Introduction: As adolescents transition from childhood to adulthood, they experience major physical, social and psychological changes, and are at heightened risk for developing mental health conditions and engaging in health-related risk behaviours. For adolescents living with HIV (ALHIV), these risks may be even more pronounced. Research shows that this population may face additional mental health challenges related to the biological impact of the disease and its treatment, the psychosocial burdens of living with HIV and HIV-related social and environmental stressors. Discussion: Psychosocial interventions delivered to adolescents can promote positive mental health, prevent mental health problems and strengthen young people’s capacity to navigate challenges and protect themselves from risk. It is likely that these interventions can also benefit at-risk populations, such as ALHIV, yet there is little research on this. There is an urgent need for more research evaluating the effects of interventions designed to improve the mental health of ALHIV. We highlight four priorities moving forward. These include: generating more evidence about preventive mental health interventions for ALHIV; including mental health outcomes in research on psychosocial interventions for ALHIV; conducting intervention research that is sensitive to differences among ALHIV populations and involving adolescents in intervention design and testing. Conclusions: More robust research on promotive and preventive mental health interventions is needed for ALHIV. Programmes should be informed by adolescent priorities and preferences and responsive to the specific needs of these groups.