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.