A baseline study has been conducted to determine the polymorphism of reverse transcriptase, protease, and envelope genes of HIV-1 isolates from 146 antiretroviral drug-naive Cambodian patients including 22 seroconverters and 124 pregnant women having been diagnosed HIV positive for less than 1 year. Amplification of at least one gene was successful for 144 isolates. All three genes were obtained for 136 isolates. Subtyping showed that CRF01_AE was predominant (130 cases). According to the ANRS September 2004 list, polymorphism substitutions (>50% versus the subtype B consensus) of CRF01_AE at drug resistance positions were observed only in protease: I13V (81%), E35D (87%), M36I (100%), R41K (96%), and H69K (100%). Two strains bore one major resistance mutation to PIs: M46I and N88D. Five other strains carried drug resistance mutations to RTIs: K70R (one strain), V75M (three strains), and K101E (one strain). Of the isolates 4.9% had drug resistance mutations to antiretroviral drugs.
The tenofovir-emtricitabine (FTC) combination was proposed during the perinatal period for prevention of motherto-child transmission (PMTCT) of HIV and/or to reduce viral resistance to nevirapine, thanks to administration to pregnant women at the start of labor (2, 5). In a previous study using a population pharmacokinetic approach, we proposed the following doses and schemes for the use of FTC during the perinatal period: for the mother, two tablets of tenofovir disoproxil fumarate (TDF) (300 mg)-FTC (200 mg) were given at the onset of labor, and if she did not deliver within the 12 h from the first administration, another two tablets of TDF-FTC, followed by one tablet per day were administered for 7 days postpartum. For the neonate, a 2-mg/kg FTC single dose within the 12 h after birth was proposed; this recommendation was based on pharmacokinetics data obtained from neonates from the transplacental transfer of FTC, after administration of FTC to the pregnant women before delivery (9). It was coadministered with a single dose of 13 mg/kg of TDF.The first objective of the following study was to evaluate our selected dose of FTC in pregnant women and their neonates. The second objective was to measure the active intracellular metabolites of FTC in neonates, as previously high intracellular phosphorylated metabolites for lamivudine triphosphate (3TC-TP) and zidovudine triphosphate (AZT-TP) during the first 2 weeks of life have been detected (7).
This study explores amino acid changes of the reverse transcriptase (rt) of CRF01_AE isolates from pregnant women naive to antiretroviral drugs before and 2, 6, and 52 weeks after exposure to single dose nevirapine (sdNVP). Results based on 51 observations showed that the proportion of isolates with nonnucleoside reverse transcriptase inhibitor (NNRTI) RMs in the group treated with sdNVP (n = 35) increased from 0% pre-NVP to 22.9% at week 2 postpartum (pp) and 22.9% at week 6 pp. In the group treated with zidovudine + sdNVP (n = 16), the proportion with RM was 31.3% and 18.8% at weeks 2 and 6 pp, respectively. Only a few RMs were still detected at week 52 pp. No apparent subtype-specific treatment-related mutations were detected. NNRTI RM occurrence in CRF01_AE strains is similar to subtype A, D, and CRF02_AG strains after exposure to antiretroviral drugs for PMTCT.
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