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UNAIDS and a broad range of partners have collaborated to establish a new set of HIV prevention targets to be achieved by 2025 as an intermediate step towards the sustainable development target for 2030. The number of new HIV infections in the world continues to decline, in part due to the extraordinary expansion of effective HIV treatment. However, the decline is geographically heterogeneous, with some regions reporting a rise in incidence. The incidence target that was agreed for 2020 has been missed. A range of exciting new HIV prevention technologies have become available or are in the pipeline but will only have an impact if they are accessible and affordable and delivered within systems that take full account of the social and political context in which most infections occur. Most new infections occur in populations that are marginalised or discriminated against due to structural, legal, and cultural barriers. The new targets imply a new approach to HIV prevention that emphasises appropriate, person-centred, prioritised, effective, combination HIV prevention within a framework that reduces existing barriers to services and acknowledges heterogeneity, autonomy, and choice. These targets have consequences for people working in HIV programmes both for delivery and for monitoring and evaluation, for health planners setting local and national priorities, and for funders both domestic and global. Most importantly, they have consequences for people who are at risk of HIV exposure and infection. Achieving these targets will have a huge impact on the future of the HIV epidemic and put us back on track towards ending AIDS as a public health threat by 2030., Author(s): Peter Godfrey-Faussett 1,2,*, Luisa Frescura 1, Quarraisha Abdool Karim 3, Michaela Clayton 4, Peter D. Ghys 1,(on behalf of the 2025 prevention targets working group) Introduction Course correction needed [...]

Author(s): Elvin H. Geng 1,*, Michael J. A. Reid 2,3, Eric Goosby 2,3, Quarraisha Abdool-Karim 4,5 Many problems underscored by the Coronavirus Disease 2019 (COVID-19) pandemic, and highlighted in other [...]

Author(s): Michael Reid 1,*, Quarraisha Abdool-Karim 2,3, Elvin Geng 4, Eric Goosby 1 COVID-19 represents the greatest threat to global public health and economies in the 21[sup.st] century. To date, [...]

Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants. [ABSTRACT FROM AUTHOR]

Repeat HIV testing is important in high HIV burden communities to enable sustainability of prevention initiatives; however, an understanding of repeat testing practices is limited. Additional HIV testing approaches may be required to increase testing. HIV self-testing is an additional testing approach, but knowledge on its potential for repeat testing is limited. This study explored repeat HIV testing practices and uptake of HIV self-testing among repeat testers, following exposure to HIV self-testing. HIV testing practices were explored at two time points. During Phase 1, eighty in-depth interviews were conducted among 40 consenting adults, and 30 telephonic contacts were completed during Phase 2. Framework analysis was used to analyse the transcripts from the in-depth interviews. The practice of repeat HIV testing is primarily influenced by HIV status awareness and risk exposure. Thirteen regular testers and one HIV naïve tester at baseline had undergone repeat testing through the use of a traditional testing approach such as HIV counselling and testing as reported in Phase 2. HIV self-testing has a role among repeat testers, but affordability and access are barriers. [ABSTRACT FROM AUTHOR]

Background: A blood-based assay that could quantify HIV susceptibility would be very valuable for HIV prevention research. Previously, we developed and validated an ex vivo, flow-based, HIV entry assay to assess genital HIV susceptibility in endocervical CD4+ T cells. Methods: Here we assessed whether this tool could be used to predict HIV risk using blood-derived CD4+ T cells in a rigorously-blinded, nested case-control study using blood samples collected from high-risk, HIV-uninfected South African women enrolled in the CAPRISA 004 clinical trial. Cases, subsequently acquiring HIV were sampled prior to HIV infection and compared with controls, who remained HIV-uninfected. The primary endpoint was ex vivo entry of a CCR5-tropic HIV founder virus into blood CD4+ T cells. Secondary endpoints included HIV entry into CD4+ central (TCM) and effector (TEM) memory T cells, and into CD4+ T cell subsets expressing CCR5, CD69, CCR6, α4β1 or α4β7. Results: Compared to bulk CD4+ T cells (4.9% virus entry), CD4+ T cells expressing CCR5, CCR6 or α4β1 and TEM were highly susceptible (15.5%, 8.8%, 8.2% and 10.8% entry, respectively, all p<0.0001), while TCM, CD69+ or α4β7+ CD4+ cells were moderately susceptible (6.4%, 6.0% and 5.8% respectively, p ≤ 0.003). While the proportion of the aforementioned highly susceptible cells correlated with overall virus entry into CD4+ T cells within an individual (r = 0.68, 0.47, 0.67, and 0.60 respectively, p<0.0001), blood virus entry did not predict subsequent mucosal HIV acquisition after controlling for sexual behaviour and condom use (OR 0.92, 95% CI 0.77–1.11, p = 0.40). Conclusions: Although virus entry identified several previously known highly susceptible cellular HIV targets, blood HIV entry did not predict subsequent heterosexual HIV acquisition. Assessment of mucosal HIV susceptibility may require sampling at the site of HIV exposure. [ABSTRACT FROM AUTHOR]

Purpose: Young women are at high risk for negative sexual health outcomes. Despite their high risk, many sexually-active women never experience negative sexual health outcomes. This study explored the ecological risk factors associated with the risk profiles of sexually-active female high school-learners in rural KwaZulu-Natal, South Africa. Methods: Using baseline data from N = 596 sexually-active school-going women, we explored the ecological factors associated with being sexually-active and managing risk successfully [SARS] or unsuccessfully [SARU]. Generalised estimated equations (GEE) were applied to data collected at multiple levels while adjusting for school and other included variables. GEE were used to calculate probability of being SARU. Results: Amongst SARU learners, 21.9% had HIV, 38.6% had HSV-2, 12.5% were pregnant, 28.7% self-reported STI symptoms and 51.9% reported a previous pregnancy. Individual-level factors had the greatest impact on being SARU. Univariate and multivariate analysis highlighted several important partner factors associated with SARU. Age was significantly associated with the risk profiles (p<0.0001), a greater proportion of SARU learners were 18 or older compared to the SARS learners. The odds of being SARU decreased when ≥18 years (aOR = 0.2577, 95% CI 0.1462–0.4542) or if not falling pregnant was important (aOR = 0.6343, 95% CI 0.4218–0.9538). Having >1 HIV test (aOR = 2.2161, 95% CI 1.3964–3.5169) increased the odds a SARU profile. Conclusion: Individual and partner level factors are important for the sexual health profile of an adolescent female. While the exploratory findings require further research; managing multiple sexual health outcomes, tailoring responses around a risk profile and including partners is essential for successful interventions. [ABSTRACT FROM AUTHOR]

In attaining UNAIDS targets of 90-90-90 to achieve epidemic control, understanding who the current utilizers of HIV treatment services are will inform efforts aimed at reaching those not being reached. A retrospective chart review of CAPRISA AIDS Treatment Program (CAT) patients between 2004 and 2013 was undertaken. Of the 4043 HIV-infected patients initiated on ART, 2586 (64.0%) were women. At ART initiation, men, compared to women, had significantly lower median CD4+ cell counts (113 vs 131 cells/mm3, p <0.001), lower median body mass index (BMI) (21.0 vs 24.2 kg/m2, p<0.001), higher mean log viral load (5.0 vs 4.9 copies/ml, p<0.001) and were significantly older (median age: 35 vs. 32 years, p<0.001). Men had higher mortality rates compared to women, 6.7 per 100 person-years (p-y), (95% CI: 5.8–7.8) vs. 4.4 per 100 p-y, (95% CI: 3.8–5.0); mortality rate ratio: 1.54, (95% CI: 1.27–1.87), p <0.001. Age-standardised mortality rate was 7.9 per 100 p-y (95% CI: 4.1–11.7) for men and 5.7 per 100 p-y (95% CI: 2.7 to 8.6) for women (standardised mortality ratio: 1.38 (1.15 to 1.70)). Mean CD4+ cell count increases post-ART initiation were lower in men at all follow-up time points. Men presented later in the course of their HIV disease for ART initiation with more advanced disease and experienced a higher mortality rate compared to women. [ABSTRACT FROM AUTHOR]

The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clade C epidemic regions in southern Africa are imminent; passive administration of the monoclonal antibody VRC01, and active immunization with a clade C modified RV144-like vaccines. We have created a large representative panel of C clade viruses to enable assessment of antibody responses to vaccines and natural infection in Southern Africa, and we investigated the genotypic and neutralization properties of recently transmitted clade C viruses to determine how viral diversity impacted antibody recognition. We further explore the implications of these findings for the potential effectiveness of these trials. A panel of 200 HIV-1 Envelope pseudoviruses was constructed from clade C viruses collected within the first 100 days following infection. Viruses collected pre-seroconversion were significantly more resistant to serum neutralization compared to post-seroconversion viruses (p = 0.001). Over 13 years of the study as the epidemic matured, HIV-1 diversified (p = 0.0009) and became more neutralization resistant to monoclonal antibodies VRC01, PG9 and 4E10. When tested at therapeutic levels (10ug/ml), VRC01 only neutralized 80% of viruses in the panel, although it did exhibit potent neutralization activity against sensitive viruses (IC50 titres of 0.42 μg/ml). The Gp120 amino acid similarity between the clade C panel and candidate C-clade vaccine protein boosts (Ce1086 and TV1) was 77%, which is 8% more distant than between CRF01_AE viruses and the RV144 CRF01_AE immunogen. Furthermore, two vaccine signature sites, K169 in V2 and I307 in V3, associated with reduced infection risk in RV144, occurred less frequently in clade C panel viruses than in CRF01_AE viruses from Thailand. Increased resistance of pre-seroconversion viruses and evidence of antigenic drift highlights the value of using panels of very recently transmitted viruses and suggests that interventions may need to be modified over time to track the changing epidemic. Furthermore, high divergence such as that observed in the older clade C epidemic in southern Africa may impact vaccine efficacy, although the correlates of infection risk are yet to be defined in the clade C setting. Findings from this study of acute/early clade C viruses will aid vaccine development, and enable identification of new broad and potent antibodies to combat the HIV-1 C-clade epidemic in southern Africa.