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. Deeks1
1University 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.
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