Addition of 7 days of zidovudine plus lamivudine to peripartum single-dose nevirapine effectively reduces nevirapine resistance postpartum in HIV-infected mothers in Malawi

Abstract

Background: We assessed whether 7 days of zidovudine + lamivudine postpartum with single-dose nevirapine at labor decreases nevirapine resistance in HIV-infected women in Malawi.

Methods: HIV-infected pregnant women receiving intrapartum single-dose nevirapine and 7 days of zidovudine + lamivudine (n = 132) and women receiving intrapartum single-dose nevirapine alone (n = 66) were followed from an antenatal visit through 6 weeks postpartum. Plasma specimens at 2 and 6 weeks postpartum were tested for genotypic resistance to nevirapine by population sequencing and sensitive real-time polymerase chain reaction. Poisson regression was used to determine predictors of postpartum nevirapine resistance.

Results: Median HIV RNA was similar at entry (4.27 log vs. 4.35 log, P = 0.87), differed at 2 weeks postpartum (2.67 log vs. 3.58 log, P < 0.0001) but not at 6 weeks postpartum (4.49 log vs. 4.40 log, P = 0.79), between single-dose nevirapine/zidovudine + lamivudine and single-dose nevirapine groups, respectively. Nevirapine resistance, measured by population sequencing and sensitive real-time polymerase chain reaction, was significantly less common in those receiving single-dose nevirapine/zidovudine + lamivudine compared with single-dose nevirapine, respectively, at 2 weeks [10% (4 of 40) vs. 74% (31 of 42), P < 0.0001] and 6 weeks postpartum [10% (11 of 115) vs. 64% (41 of 64), P < 0.0001; adjusted relative risk = 0.18, 95% confidence interval (0.10 to 0.34)].

Conclusions: The significant decrease in nevirapine resistance conferred by 1 week of zidovudine + lamivudine should help policymakers optimize peripartum HIV prophylaxis recommendations.

Trial registration: ClinicalTrials.gov NCT00164762.

Figure 1. Median viral load† and percent of women with detectable nevirapine‡ (NVP) by drug regimen among HIV-infected mothers*, Lilongwe, Malawi

*Among women with testable plasma specimens at 2 weeks (sdNVP: n=45; sdNVP/ZDV+3TC: n=53) and 6 weeks postpartum (sdNVP: n=65; sdNVP/ZDV+3TC: n=120); ^†Chi square p-value for viral load: antenatal: p=0.87; 2 weeks postpartum: p<0.0001, 6 weeks postpartum: p=0.79 ^‡Chi square p-value for NVP concentration: delivery: p=0.47; 2 weeks postpartum: p<0.0001; 6 weeks postpartum: p=0.79

Figure 2. Prevalence of NVP resistance mutations by drug regimen among HIV-infected mothers*, Lilongwe, Malawi

*Among women with testable plasma specimens at 2 weeks (sdNVP: n=45; sdNVP/ZDV+3TC: n=53) and 6 weeks postpartum (sdNVP: n=65; sdNVP/ZDV+3TC: n=120) and no NVP resistance at an antenatal visit