TY - JOUR
T1 - Insights to a Cure
T2 - Unique Controller Phenotypes in the Rotterdam HIV-2 Cohort
AU - Hensley, Kathryn S.
AU - Gruters, Rob A.
AU - Van Nood, Els
AU - De Mendonça Melo, Mariana
AU - Overmars, Ronald J.
AU - Górska, Alicja U.
AU - Rokx, Casper
AU - Lungu, Cynthia
AU - Van De Vijver, David A.M.C.
AU - Mesplède, Thibault
AU - Van Kampen, Jeroen J.A.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/7
Y1 - 2025/7
N2 - 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 <200copies/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.
AB - 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 <200copies/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.
UR - https://www.scopus.com/pages/publications/105009778571
U2 - 10.1093/ofid/ofaf336
DO - 10.1093/ofid/ofaf336
M3 - Article
C2 - 40599486
AN - SCOPUS:105009778571
SN - 2328-8957
VL - 12
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 7
M1 - ofaf336
ER -
