Temporal trends in viral SetPoint and peak CD4 cell count soon after HIV-1 seroconversion.

Area of Science:

• Virology and Immunology
• Epidemiology
• Public Health

Background:

• HIV-1 virulence may have changed over time due to widespread antiretroviral therapy (ART) availability.
• Prognostic markers, such as setpoint viral load (SPVL) and peak CD4 count, offer insights into HIV-1 virulence.
• Understanding temporal trends in HIV-1 virulence is crucial for public health strategies.

Purpose of the Study:

• To investigate temporal changes in HIV-1 virulence using prognostic markers.
• To analyze these changes across different subgroups of individuals.
• To assess the impact of ART availability on HIV-1 virulence over time.

Main Methods:

• An observational cohort study utilizing data from the CASCADE Collaboration.
• Analysis of 21,933 participants with well-estimated HIV-1 seroconversion dates (1980-2014).
• Piecewise linear mixed models were used to analyze setpoint viral load (SPVL) and peak CD4 count, adjusting for covariates.

Main Results:

• Setpoint viral load (SPVL) increased and peak CD4 count declined until approximately 2000, then stabilized with a mild reversal after 2005.
• Estimated average SPVL rose from 3.2 log10 copies/mL in 1980 to 4.3 log10 copies/mL in 2005, then slightly decreased.
• Peak CD4 count decreased from 960 cells/μL in 1980 to 521 cells/μL in 2005, followed by a slight increase.

Conclusions:

• HIV-1 virulence, as indicated by SPVL and peak CD4, stabilized between 2000-2005, suggesting potential viral adaptation.
• A subsequent trend reversal, most notable in men who have sex with men (MSM), necessitates ongoing surveillance.
• These findings highlight the dynamic nature of HIV-1 in response to population-level interventions.