OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression.

DESIGN: An observational cohort collaboration study.

METHODS: A total of 158 385 pairs of consecutive viral load and CD4(+) cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual changes and factors associated with these changes were estimated using generalized estimating equations.

RESULTS: Viral load continued to rise at a mean [95% confidence interval (CI)] rate of 0.091 (0.086-0.096) log10 copies/ml per year. A faster rise in viral load was significantly associated with older age, such that for every 10 years older, it was a mean 0.022 log10 copies/ml per year greater. The mean (95% CI) CD4(+) cell count change was -78.0 (-80.1 to -76.0) cell/μl per year and it was strongly associated with a higher current viral load: for every 1 log10 copies/ml higher, CD4(+) cell count declined by an additional 37.6 cells/μl per year (P < 0.001). Current viral load was a stronger predictor of CD4(+) cell count depletion than baseline viral load. Neither sex, race nor transmission by injecting drug use was associated with change in either the viral load or CD4(+) cell count.

DISCUSSION: We found that in ART-naive individuals, viral load continues to increase over time and more sharply in those who are older. Our results also suggest that higher current viral load is strongly associated with ongoing rate of CD4(+) cell count depletion.