Temporal trends in viral setpoint and peak CD4+ cell count soon after HIV-1 seroconversion

OBJECTIVES: To examine whether HIV-1 virulence, as measured by prognostic markers soon after seroconversion, has changed over time and across subgroups in the context of widespread ART availability. DESIGN: Observational cohort study of individuals with well estimated HIV-1 seroconversion dates recruited from clinics in eight European countries and Canada (CASCADE Collaboration). METHODS: We analyzed data from 21 933 participants who seroconverted 1980-2014, while ART-naïve and AIDS-free. Piecewise linear mixed models with one knot at 1 year after seroconversion for log 10 HIV-1 RNA (setpoint viral load, SPVL) and 4 months for square-root CD4 + cell count (peak CD4) were fitted. Models adjusted for age, sex/probable exposure route, region of origin, diagnosis during acute infection, and assay type. RESULTS: SPVL increased and peak CD4 declined over time until approximately 2000, then stabilized, with a mild reversal after 2005. Estimated (95% CI) average SPVL for those seroconverting on 1/1/1980, 1/1/1995, 1/1/2005, and 31/12/2014 was 3.2 (3.0-3.4), 4.0 (3.9-4.1), 4.3 (4.2-4.4), and 4.2 (4.1-4.3) log10 copies/ml, respectively. Corresponding estimates for peak CD4 were 960 (898-1025), 615 (584-648), 521 (492-551), and 560 (526-594) cells/μl. The increase in SPVL up to 2005 was less pronounced in European/North American MSM (1.0 log 10 copies/ml) than in men and women with heterosexual exposure from the same region or from Africa (1.5 and 1.4 log 10 copies/ml, respectively). CONCLUSIONS: SPVL and peak CD4 stabilized by 2000-2005, consistent with HIV-1 adaptation to the population. The subsequent trend reversal, most evident among MSM, warrants ongoing monitoring.