HIV Pathogenesis

The HIV Pathogenesis Programme is dedicated to understanding the earliest stages of HIV infection and the host–virus interactions that shape disease progression, immune control, and long-term outcomes. This department leads several key studies, including the CAPRISA 002 Acute Infection Cohort, the CAPRISA 012C broadly neutralizing antibody trials, the NeutART trial focused on HIV cure strategies.

CAPRISA 002: The Acute HIV Infection Study

This flagship study, initiated in 2004, has made significant contributions to global understanding of acute HIV-1 subtype C infection. The primary aim is to investigate viral set point dynamics, clinical progression, and the viral, host genetic, and immunological factors that influence disease outcomes.

Key findings from CAPRISA 002 include:

Symptomatic seroconversion occurred in 57% of women, with a rapid depletion of CD4+ T cells—up to 50% lost within the first weeks post-infection.
High early viral loads correlated with symptom severity but were not predictive of long-term disease progression.
Over 50% of participants reached the ART initiation threshold (CD4 <350 cells/mm³) within two years, highlighting the aggressive course of untreated subtype C infection.
Sexually transmitted infections (STIs) diagnosed in the lab were strongly associated with HIV acquisition, while self-reported vaginal discharge was not a reliable predictor.
Elevated genital tract cytokines during early infection were linked to increased viral loads and faster CD4+ T cell decline, suggesting that inflammation may facilitate HIV pathogenesis.

Virologically, ~80% of participants were infected with a single founder virus. Deep sequencing revealed early immune escape mutations driven predominantly by cytotoxic T lymphocyte (CTL) responses. These mutations, some unique to subtype C, were associated with transient loss of viral control. Notably, certain HLA class I genotypes were linked to mutations in the transmitted virus, potentially conferring a survival advantage to HIV.

A landmark achievement from CAPRISA 002 was the observation that approximately 20% of participants developed broadly neutralizing antibodies (bnAbs) within three years of infection. These bnAbs evolved through selective pressure against early strain-specific antibodies targeting regions such as C3-V4 and V1/V2 on the HIV envelope. This has informed the identification of bnAb epitopes that has guided the development of next-generation antibody-based interventions, such as those being evaluated in the CAPRISA 012C and NeutART trials.

Broader Vision

Through these integrated clinical studies, CAPRISA continues to advance the understanding of HIV pathogenesis with a focus on the earliest events post-infection. The programme is actively translating these insights into preventive, therapeutic and cure strategies, including bnAb-based interventions, HIV cure research, artificial intelligence, machine learning and personalised treatment approaches for women in high-burden settings.