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

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Human Immunodeficiency Virus type 2 (HIV-2) is less common than HIV-1 but shows a higher rate of elite controllers (ECs).
• Elite controllers naturally suppress HIV without antiretroviral therapy (ART), a rare phenomenon in HIV-1.
• Studying HIV-2 ECs may reveal viral control mechanisms and pathways toward an HIV cure.

Purpose of the Study:

• To retrospectively characterize a cohort of people with HIV-2.
• To identify categories of elite controllers (ECs) within this cohort.
• To analyze viral loads, CD4+ T-cell counts, and responses to antiretroviral therapy (ART) in HIV-2 patients.

Main Methods:

• Retrospective analysis of a cohort of 52 individuals with HIV-2 receiving care between 1989 and 2023.
• Categorization of elite controllers (ECs) based on plasma viral loads (<200 copies/mL) and CD4+ T-cell counts (>350 cells/mm³).
• Assessment of various HIV-2 disease progression phenotypes, including nonviremic progressors and recontrollers.

Main Results:

• Thirteen out of 40 analyzed participants were identified as elite controllers (ECs).
• Diverse HIV-2 trajectories were observed, including nonviremic progressors, those losing control, classical progressors, and a unique recontroller.
• The cohort was primarily of West African origin (80.8%), with a median follow-up of 16 years.

Conclusions:

• The study identified distinct clinical and virological trajectories among HIV-2 elite controllers (ECs).
• Understanding these diverse HIV-2 control mechanisms is crucial for informing treatment strategies.
• Further research into ECs could contribute to developing a functional cure for HIV.