Envelope coreceptor tropism, drug resistance, and viral evolution among subtype C HIV-1-infected individuals receiving nonsuppressive antiretroviral therapy.
BACKGROUND
In resource-constrained settings, antiretroviral treatment (ART) is often continued based on clinical and CD4 responses, without virologic monitoring. ART with incomplete viral suppression was assessed in 27 subjects with subtype C HIV-1.


METHODS
Plasma HIV-1 RNA, drug resistance, viral tropism, and evolution in polymerase (pol) and envelope (env) genes were measured. The association between these viral parameters and CD4 cell change over time was analyzed using linear regression models.


RESULTS
Increased area under the curve of HIV-1 RNA replication was a predictor of lower CD4 cell gains (P < 0.007), while less drug resistance measured as a genotypic susceptibility score (GSS) (P = 0.065), and lower rates of evolution in pol and env genes (P = 0.08 and 0.097, respectively) measured as genetic distance were modestly associated with increasing CD4 cell counts. Evolution of pol and env were correlated (R2 = 0.48, P = 0.005), however, greater evolution was identified in env vs. pol (P < 0.05). CXCR4-usage (X4) was detected in 14/27 (52%) but no differences in CD4 cell change or plasma viremia were associated with X4-usage.


CONCLUSIONS
Among subtype C HIV-1 infected patients in Zimbabwe receiving incompletely suppressive ART, higher virus replication and lower CD4 cell gains were associated with drug resistance and evolution of polymerase and envelope.
Kassaye
Seble
S
Department of Medicine, Division of Infectious Diseases, Stanford University Medical Center, Stanford, CA 94305, USA. skassaye@stanford.edu
Johnston
Elizabeth
E
McColgan
Bryan
B
Kantor
Rami
R
Zijenah
Lynn
L
Katzenstein
David
D
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015752:Genes, env / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D018523:Tropism
D019380:Anti-HIV Agents; D012367:RNA, Viral