Elsevier

The Lancet HIV

Volume 5, Issue 1, January 2018, Pages e35-e44
The Lancet HIV

Articles
Detection and treatment of Fiebig stage I HIV-1 infection in young at-risk women in South Africa: a prospective cohort study

https://doi.org/10.1016/S2352-3018(17)30146-7Get rights and content

Summary

Background

HIV incidence among young women in sub-Saharan Africa remains high and their inclusion in vaccine and cure efforts is crucial. We aimed to establish a cohort of young women detected during Fiebig stage I acute HIV infection in whom treatment was initiated immediately after diagnosis to advance research in this high-risk group.

Methods

945 women aged 18–23 years in KwaZulu-Natal, South Africa, who were HIV uninfected and sexually active consented to HIV-1 RNA testing twice a week and biological sampling and risk assessment every 3 months during participation in a 48–96 week life-skills and job-readiness programme. We analysed the effect of immediate combination antiretroviral therapy (ART) on viraemia and immune responses, sexual risk behaviour, and the effect of the socioeconomic intervention.

Findings

42 women were diagnosed with acute HIV infection between Dec 1, 2012, and June 30, 2016, (incidence 8·2 per 100 person-years, 95% CI 5·9–11·1), of whom 36 (86%) were diagnosed in Fiebig stage I infection with a median initial viral load of 2·97 log10 copies per mL (IQR 2·42–3·85). 23 of these 36 women started ART at a median of 1 day (1–1) after detection, which limited the median peak viral load to 4·22 log10 copies per mL (3·27–4·83) and the CD4 nadir to 685 cells per μL (561–802). ART also suppressed viral load (to <20 copies per mL) within a median of 16 days (12–26) and, in 20 (87%) of 23 women, prevented seroconversion, as shown with western blotting. 385 women completed the 48 week socioeconomic intervention, of whom 231 were followed up for 1 year. 202 (87%) of these 231 women were placed in jobs, returned to school, or started a business.

Interpretation

Frequent HIV screening combined with a socioeconomic intervention facilitated sampling and risk assessment before and after infection. In addition to detection of acute infection and immediate treatment, we established a cohort optimised for prevention and cure research.

Funding

Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases, International AIDS Vaccine Initiative, Wellcome Trust, Howard Hughes Medical Institute.

Introduction

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.

Section snippets

Study design and participants

FRESH is an ongoing prospective cohort study in KwaZulu-Natal, South Africa, designed to diagnose acute HIV infection in young at-risk women, obtain blood and mucosal samples before and after infection, and enable study of HIV pathogenesis and biological and behavioural risk factors for HIV acquisition, as well as research on vaccine and cure strategies. Eligible women were HIV uninfected, aged 18–23 years, sexually active, not pregnant, non-anaemic (haemoglobin ≥10 g/L), without other barriers

Results

Between Dec 1, 2012, and June 30, 2016, 1290 women aged 18–23 years were screened for HIV-1 infection, 945 (73%) of whom were eligible and enrolled (figure 1; table 1). Median age was 21 years. Most women had regular or steady partners; however, cohabitation was uncommon (table 1). At enrolment, no participants were employed or attending school full time.

42 (4%) participants had acute HIV infection after enrolment, reflecting an incidence of 8·2 per 100 person-years (95% CI 5·9–11·1). The

Discussion

Young, socioeconomically disadvantaged women at high risk of HIV infection are able to adhere to frequent follow-up and collection of biological specimens, thereby allowing very early detection of acute HIV infection. 42 women were diagnosed with acute HIV infection, many of whom had initial viral loads of less than 100 RNA copies per mL of plasma (1·99 log10 copies per mL). 36 (86%) of the 42 women were in Fiebig stage I HIV infection, of whom 23 were started on immediate ART. These women

References (30)

  • TJ Hope et al.

    A shot in the arm for HIV prevention? Recent successes and critical thresholds

    AIDS Res Hum Retroviruses

    (2015)
  • B Ensoli et al.

    Challenges in HIV vaccine research for treatment and prevention

    Front Immunol

    (2014)
  • V Jain et al.

    Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size

    J Infect Dis

    (2013)
  • A Saez-Cirion et al.

    Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study

    PLoS Pathog

    (2013)
  • AL Hill et al.

    Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1

    Proc Natl Acad Sci USA

    (2014)
  • Cited by (0)

    View full text