Role of Baseline pol Genotype in HIV-1 Fitness Evolution.

Department of Virology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 08/2003; 33(4):448-60. DOI: 10.1097/00126334-200308010-00005
Source: PubMed

ABSTRACT Viral fitness can be modified upon development of antiretroviral drug resistance, usually by selection of compensatory mutations. In this study, we have used HIV-1 isolates from individuals receiving a protease inhibitor (PI)-based regimen to analyze the impact of basal genetic background on viral fitness evolution. Paired plasma samples and HIV-1 isolates were obtained from 10 PI-naive HIV-infected individuals enrolled in 2 different studies of combination antiretroviral therapy. Genomic regions from pol and env were sequenced. Viral fitness was measured using growth competition experiments followed by heteroduplex tracking analysis. Baseline genotypic analyses of pol showed that 9 of 10 viruses had a different degree of secondary mutations in the protease gene at codons associated with PI resistance (i.e., 10I, 36I, 63P, 71T, and 77I). After 48 weeks of PI-based therapy, a strong correlation was observed between protease genetic divergence and viral fitness difference (r = 0.78, P = 0.03), but not with reverse transcription or Env divergence, suggesting that genotypic changes in the protease gene were driving HIV-1 evolution in these patients. As expected, an inverse correlation was observed between the number of protease and reverse transcription primary mutations and viral fitness (r = -0.65, P < 0.0001). However, our results suggest that the preexistence of secondary mutations in protease genetic background may have implications in HIV-1 fitness evolution and virologic response to antiretroviral therapy.

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Available from: Hector Rafael Rangel, Jan 16, 2015
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    • "Furthermore, in the context of transmission, 'fitness' per se may not necessarily equate to infectivity. The impact of measures of fitness on the transmission of resistant HIV, remains an area of research activity (Brenner et al., 2002; Goudsmit et al., 1997; Martinez-Picadao et al., 1999; Simon et al., 2003; Weber et al., 2003). Since transmission of resistance is now well documented, the use of baseline resistance testing of newly diagnosed HIV infections is likely to become more routine (Little et al., 2002), especially where some resistance mutations appear to persist or become 'fixed' within a local HIV-infected population (Taylor et al., 2003), making the transmission of HIV resistance more likely. "
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