Antiretroviral therapy for HIV controllers: indications and outcomes in the French ANRS-CO21 CODEX cohort


BACKGROUND: Less than 1% of HIV-infected individuals are able to achieve spontaneous viral control without requiring antiretroviral therapy (ART). Whether these HIV controllers (HIC) are at risk of HIV-associated comorbidities and could benefit from ART is debated, but recent studies reported decreased T-cell activation upon ART initiation. We report the frequency of ART initiation, reasons to treat, treatment outcome on immunovirological parameters, and rate of side-effects and treatment discontinuation in the French cohort of HIC.
METHODS: Participants included in the ANRS CODEX cohort of HIC were prospectively followed. ART initiation, indication, discontinuation, non-AIDS-defining events, side-effects, and immunovirological parameters were recorded. Undetectable HIC (u-HIC) were defined as participants with strictly undetectable viral loads based on routinely used assays throughout the follow-up and blipper HIC (b-HIC) as participants with possible detectable viral loads above the detection threshold during follow-up.
RESULTS: Among 302 HIC followed for a median of 14.8 years [10.3-20.2], 90 (30%) received ART (7 u-HIC and 83 b-HIC). The main reasons for ART initiation were decreased CD4 T-cell counts (n=36, 40%), loss of virological control (n=13, 14%), and non-AIDS-defining events (n=12, 13%). Sixteen (18%) participants experienced 17 grade 1-2 adverse events. In b-HIC, ART slightly increased the CD4/CD8 ratio (median +0.19, p<0.0001) and decreased the frequency of circulating CD38+ HLA-DR+ CD4 and CD8 lymphocytes (median -0.75%, p=0.003, and -2%, p<0.0001, respectively), but these changes were not observed for treated u-HIC. Thirteen (14%) participants discontinued ART (5 (38%) because of side-effects, and 10 remained HIC after treatment cessation (median follow-up: 305 days [235-728]).
CONCLUSIONS: Only 30% of participants in this large cohort of HIC required ART during a median follow-up of 14.8 years. These results show that HIC status is very stable and can be maintained for decades and vouch for a patient-centered treatment decision based on the individual benefit/risk balance.