High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy.

ABSTRACT: Objectives:Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. Methods:At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ?6?months; GVL when PVL >2000?copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000?copies/mL. Wilcoxon rank-sum and Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Inter-compartmental resistance discordance was evaluated using generalized estimating equations. Results:Of 200 women, 37% had detectable (>400?copies/mL) PVL and 31% had PVL >1000?copies/mL. Of women with detectable PVL, 74% had PVL >2000?copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34?years, median ART duration of 33?months, median CD4 count of 217?cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10?copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. Conclusions:We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.

SUBMITTER: Saravanan S 

PROVIDER: S-EPMC6927885 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature