Insights to a Cure: Unique Controller Phenotypes in the Rotterdam HIV-2 Cohort

Background HIV-2, although less common than HIV-1, exhibits a higher proportion of elite controllers (ECs), who can suppress HIV without antiretroviral therapy (ART), a phenomenon rarely observed in HIV-1. Studying ECs could yield insights into viral control mechanisms and potentially lead to a cure. Methods We retrospectively characterized a cohort of people with HIV-2 who received care at the Erasmus University Medical Center, Rotterdam, Netherlands. The aim was to identify categories of ECs based on plasma viral loads, CD4+ T-cell count, and responses to ART. Results Between 1989 and 2023, 52 people with HIV-2 were included, primarily of West African origin (80.8%). Follow-up ranged from <1 to 32 years (median, 16 years). Seven participants were lost to follow-up (13.5.%), and 18 participants died (34.6%), 7 before ART availability due to AIDS. The remaining 40 participants were included in the detailed analysis. Thirteen were ECs with CD4+ T cells >350 cells/mm3 and viral loads <200 copies/mL without use of ART. Four participants progressed to CD4+ T cells <350 cells/mm3 without symptoms of HIV despite undetectable viral loads (nonviremic progressors). Three individuals demonstrated EC status for at least 5 years but lost viral and immunologic control. Nineteen participants exhibited a classical phenotype of viremic progression. Five participants had HIV-1 and HIV-2. Finally, 1 participant had a unique phenotype with loss of control with an unexplained rebound in viremia, followed by resuppression without ART for >10 years (recontroller). Conclusions These data highlight relevant trajectories among ECs. Understanding the underlying mechanisms can inform decisions on treatment and contribute to finding a cure for all people with HIV.