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

Abstract

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.

Figure 1.. Study profile

ART=combination antiretroviral therapy. *Early ART was defined as treatment initiated during acute HIV infection, immediately after detection of HIV RNA.

Figure 2.. Effect of early treatment on viral load and CD4 cell dynamics in acute HIV infection.

(A) The plasma viral load for 14 participants untreated during acute HIV infection is plotted against days after detection of HIV-1 RNA, with day 0 being the day of detection. (B) Effect of ART on viral load for 28 participants initiated on treatment immediately after detection of HIV-1 RNA; the horizontal boxes show median time to viral suppression (<20 copies per mL) for Fiebig stage I (16 days, IQR 12–26, range 6–78) versus Fiebig stage II-V (25 days, 19–38, 9–72). (C) Effect of immediate ART on viral-load dynamics in 23 participants with Fiebig stage I acute HIV infection compared with 13 untreated women with Fiebig stage I infection; median viral load is plotted against longitudinal sampling timepoints; the vertical bars on each curve represent the range for viral load at each timepoint. (D) Reduction of peak HIV viraemia by immeidate initiation of ART in participants detected during Fiebig stage I acute HIV infection; median peak viral load (bold lines) and IQR (thin lines) are shown for 13 untreated (median 7.11 log₁₀ copies per mL, IQR 6.98–7.48) and 23 early treated (4.22 log₁₀ copies per mL, 3.27–4.83) participants (p<0.0001). (E) Dynamics of the CD4 cell count for 13 untreated and 23 early treated participants with Fiebig stage I acute HIV infection; pre-infection CD4 was the absolute CD4 cell count from the sampling point preceding detection of acute HIV infection; nadir CD4 was the lowest absolute CD4 cell count measured after detection of infection; rebound CD4 cell count was the absolute count collected at the scheduled 42 days sampling point. ART=combination antiretroviral therapy.

Figure 3.. Effect of ART initiated during acute HIV infection on western blot development

Longitudinal western-blot testing is shown for 36 participants with Fiebig stage I HIV infection, of whom 13 were untreated and 23 received immediate ART. *Fiebig stage III. †Fiebig stage V.