Despite advances in prevention methods and expanded access to combination antiretroviral therapy (ART), HIV incidence remains high in key populations, particularly young women in sub-Saharan Africa.1 Therefore, development of effective interventions targeting this risk group is imperative.2 Improved understanding of the behavioural factors and biological mechanisms underlying increased HIV acquisition risk in young women is important for prevention strategies.3 Furthermore, because of inherent adverse effects of lifelong therapy, and persistent immune activation, an HIV cure is needed.4, 5, 6, 7 Investigation of the earliest immunological and virological events after HIV infection is essential to vaccine and cure research. ART initiation during the earliest stages of acute HIV infection can reduce transmission risk, viral reservoir size, and T-cell activation and, in some individuals, lead to long-term viral remission after withdrawal of treatment.8, 9, 10, 11 However, detection and treatment during Fiebig stage I infection, when viraemia first becomes detectable, is challenging.
One approach to the detection of acute HIV infection during Fiebig stage I is to test uninfected individuals who are at high risk of infection, which requires a cohort capable of adhering to a frequent surveillance schedule. In South Africa, gender inequalities and poor access to education and economic opportunities place young women at disproportionately high risk of HIV infection.12, 13 In the South African province KwaZulu-Natal, HIV incidence in young women is around 10·0 per 100 person-years.14 Surveillance testing in this group could enable detection during acute HIV infection, even if combined with interventions to reduce HIV incidence. Collection of blood and mucosal tissue before infection would permit identification of factors associated with acquisition and early interactions between host and virus that determine disease progression. Treatment initiated immediately after detection would be expected to limit viraemia and establishment of viral reservoirs. Moreover, because research on acute HIV infection tends to be done mainly in men who have sex with men, serodiscordant couples, and blood donors,15 inclusion of women, who bear a disproportionate burden of HIV globally, is vitally important.
Research in context
Evidence before this study
We searched PubMed between Jan 1, 2008, and Jan 31, 2017, for original and review English language articles on acute HIV infection, HIV in young women in sub-Saharan Africa, HIV susceptibility and incidence in young women, HIV cure strategies, and antiretroviral therapy (ART) for acute HIV infection using the search terms “acute HIV,” “infection,” “HIV eradication,” “HIV cure strategies,” “immediate ART,” “early ART,” “HIV cure,” “HIV vaccine,” “HIV reservoirs,” and “Fiebig stage I HIV infection”. We found several studies of acute HIV infection, but these studies had substantial limitations in that, in almost all studies, no mucosal or peripheral blood samples were taken before infection that could help unravel biological and behavioural risk factors for HIV acquisition. Furthermore, previous studies of acute HIV infection did not have frequent sampling during the critical stage before peak viraemia and, therefore, missed the opportunity to explore virological and host events associated with subsequent control of HIV. Although early initiation of ART has been proposed as a strategy to achieve a functional cure and to understand the mechanisms of viral reservoir formation, we found no studies of this strategy in sub-Saharan Africa, and, even in the most resource-rich settings, this strategy has only been attempted after seroconversion when the reservoir might already be well established.
Added value of this study
We showed that Fiebig stage I acute HIV infection could be identified in a high-incidence, resource-poor setting by frequent sampling before and immediately after infection. Our observations of CD4 cell preservation and reduction of peak viraemia with combination ART might have important implications for attempts to inhibit reservoir formation and subsequently purge the virus to achieve a functional cure. A socioeconomic empowerment programme, designed to coincide with sampling before and after infection, might facilitate HIV prevention and pathogenesis research.
Implications of all the available evidence
We have established a unique cohort optimised for prevention, vaccine, and cure research in a highly endemic, resource-poor setting.
With the aim of detecting acute HIV infection during Fiebig stage I, we established the Females Rising through Education, Support, and Health (FRESH) study in KwaZulu-Natal to enrol young, HIV-uninfected women at risk of infection. We hypothesised that HIV RNA testing twice a week in a high-risk cohort, coupled with frequent, longitudinal collection of biological specimens before and immediately after infection, would provide the opportunity for HIV prevention and cure research in this at-risk population. To encourage participant enrolment and adherence to the protocol, we designed a socioeconomic intervention, scheduled to coincide with study visits, which delivered tangible and sustained benefit to participants.