Abstract

Association between acquired HIV drug resistance and HIV plasma RNA and CD4+ cell counts during early infection and during the set point phase

Presented by Vivek Jain (United States).

V. Jain¹, E. Vittinghoff², F. Hecht¹, S. Deeks<sup>1

1</sup>University of California San Francisco (UCSF), HIV/AIDS Division, San Francisco General Hospital, San Francisco, United States, ²University of California San Francisco (UCSF), Department of Epidemiology and Biostatistics, San Francisco, United States

Background: Drug resistance mutations are often associated with reduced fitness in vitro. The in vivo consequences of these mutations are not certain. We evaluated the impact of transmitted drug resistance (TDR) on viral load (VL) and CD4 cell counts over time in patients naive to antiretroviral therapy (ART).
Methods: Genotypic resistance measurements were performed at baseline on a large cohort of individuals identified during acute/early infection (UCSF Options cohort). We used linear mixed models with cubic splines to compare secular patterns in logVL and square root CD4 (sqrtCD4) in those with and without transmitted drug resistance, censoring data upon ART initiation. In addition, average logVL and sqrtCD4 levels were compared during set point (6 months to 2 years).
Results: Of 556 individuals with genotypic data available, 104 (19%) had transmitted drug resistance. Approximately 60 days after the estimated infection date, VL was higher in WT than in TDR (0.38 logs, p< 0.001), as well as in subgroups with NRTI (0.32 logs, p=0.02) and PI (0.56 logs, p=0.001) resistance. Individuals with NNRTI resistance had a trend suggesting higher VL (0.27 logs, p=0.11). These differences in VL waned over time; VL was not significantly different between groups at 180 and 360 days. There were no differences in CD4 cell counts, either early after infection or during set point.
Conclusions: Patients with transmitted NRTI and PI, but not NNRTI, resistance mutations have lower viral loads during the acute phase of infection; this effect, however, is not sustained. These data provide evidence that drug resistance mutations have an in vivo impact on viral fitness. The waning of the differences in viral load over time suggests that further viral evolution likely attenuates the impact of drug resistance mutations, either through reversion of mutations to wild-type, or through other genetic changes that compensate for fitness costs.