Emergence and Persistence of Minor Drug-Resistant HIV-1 Variants in Ugandan Women after Nevirapine Single-Dose ProphylaxisReport as inadecuate




Emergence and Persistence of Minor Drug-Resistant HIV-1 Variants in Ugandan Women after Nevirapine Single-Dose Prophylaxis - Download this document for free, or read online. Document in PDF available to download.

Background

Nevirapine NVP single-dose is still a widely used antiretroviral prophylaxis for the prevention of vertical HIV-1 transmission in resource-limited settings. However, the main disadvantage of the Non-nucleoside Reverse Transcriptase Inhibitor NNRTI NVP is the rapid selection of NVP-resistant virus with negative implications for subsequent NNRTI-based long-term antiretroviral therapy ART. Here, we analysed the emergence of drug-resistant HIV-1 including minor variants in the early phase after NVP single-dose prophylaxis and the persistence of drug-resistant virus over time.

Methods and Findings

NVP-resistant HIV-1 harbouring the K103N and-or Y181C resistance mutations in the HIV-1 reverse transcriptase gene was measured from 1 week up to 18 months after NVP single-dose prophylaxis in 29 Ugandan women using allele-specific PCR assays capable of detecting drug-resistant variants representing less than 1% of the whole viral population. In total, drug-resistant HIV-1 was identified in 18-29 62% women; rates increased from 18% to 38% and 44% at week 1, 2, 6, respectively, and decreased to 18%, 25%, 13% and 4% at month 3, 6, 12 and 18, respectively. The proportion of NVP-resistant virus of the total viral population was significantly higher in women infected with subtype D median 40.5% as compared to subtype A median 1.3%; p = 0.032, Mann-Whitney U test. 33% of resistant virus was not detectable at week 2 but was for the first time measurable 6–12 weeks after NVP single-dose prophylaxis. Three 10% women harboured resistant virus in proportions >10% still at month 6.

Conclusions

Current WHO guidelines recommend an additional postnatal intake of AZT and 3TC for one week to avoid NVP resistance formation. Our findings indicate that a 1-week medication might be too short to impede the emergence of NVP resistance in a substantial proportion of women. Furthermore, subsequent NNRTI-based ART should not be started earlier than 12 months after NVP single-dose prophylaxis.



Author: Andrea Hauser, Kizito Mugenyi, Rose Kabasinguzi, Claudia Kuecherer, Gundel Harms, Andrea Kunz

Source: http://plos.srce.hr/



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