Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose nevirapine is substantially underestimated.
ABSTRACT Conventional sequence analysis detects human immunodeficiency virus (HIV)-1 drug resistance mutations in approximately 40% of women shortly after they receive intrapartum single-dose nevirapine (SD-NVP). Using sensitive real-time polymerase chain reaction assays for the K103N and Y181C resistance mutations, we tested genotyped virus before and after SD-NVP in 50 South African women infected with HIV-1 subtype C. By sequence analysis, 40 women had no detectable resistance mutations, and an additional 6 women were negative for Y181C after SD-NVP. We found K103N in 16 (40%) of 40 women and Y181C in 5 (11%) of 46 women at 6-36 weeks postpartum. Clonal sequencing confirmed K103N in 5 of 5 representative samples and Y181C in 4 of 4 samples. Four of the 5 women with newly identified Y181C also had K103N. These findings indicate that resistance mutations emerged in at least 65% of the women after SD-NVP and emphasize the importance of further research to determine the clinical implications.
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ABSTRACT: The Thai HIV programme is a leader in the public health approach to HIV treatment. Starting at transmission of HIV and ending with transition to adult services this paper assesses the paediatric HIV treatment continuum from three perspectives: service-user, provider and policy maker, to understand what works well and why.PLoS ONE 01/2014; 9(6):e99061. · 3.53 Impact Factor
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ABSTRACT: Background. The iPrEx study demonstrated that oral FTC/TDF as pre-exposure prophylaxis (PrEP) protects against HIV acquisition in men who have sex with men and transgender women. Selection for drug resistance could offset PrEP benefits.Methods. Phenotypic and genotypic clinical resistance assays characterized major drug resistant mutations. Minor variants with FTC/TDF mutations K65R, K70E, M184 V/I were measured using 454 deep sequencing and a novel AS-PCR diagnostic tolerant to sequence heterogeneity.Results. Control of primer-binding site heterogeneity resulted in improved accuracy of minor variant measurements by AS-PCR. Of the 131 on-study infections (48 randomized to FTC/TDF), none showed FTC/TDF mutations by clinical assays despite detectable drug within the infection window in 8 participants. Two randomized to FTC/TDF had minor variant M184I detected at 0.53% by AS-PCR or 0.75% by deep sequencing, only one of which had low but detectable drug prior to seroconversion. Among those with acute infection at randomization to FTC/TDF, M184 V or I mutations that were predominant at seroconversion waned to background levels within 24 weeks after discontinuing drug.Conclusions. Drug resistance was rare in iPrEx on-study FTC/TDF-randomized seroconverters, and only as low-frequency minor variants. FTC resistance among those initiating PrEP with acute infection waned rapidly after drug discontinuation.Trial registration. ClinicalTrials.gov identifier: NCT00458393.The Journal of Infectious Diseases 04/2014; · 5.85 Impact Factor
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ABSTRACT: Human immunodeficiency virus (HIV) causes approximately 2.5 million new infections every year, and nearly 1.6 million patients succumb to HIV each year. Several factors, including cross-species transmission and error-prone replication have resulted in extraordinary genetic diversity of HIV groups. One of these groups, known as group M (main) contains nine subtypes (A-D, F-H and J-K) and causes ~95% of all HIV infections. Most reported data on susceptibility and resistance to anti-HIV therapies are from subtype B HIV infections, which are prevalent in developed countries but account for only ~12% of all global HIV infections, whereas non-B subtype HIV infections that account for ~88% of all HIV infections are prevalent primarily in low and middle-income countries. Although the treatments for subtype B infections are generally effective against non-B subtype infections, there are differences in response to therapies. Here, we review how polymorphisms, transmission efficiency of drug-resistant strains, and differences in genetic barrier for drug resistance can differentially alter the response to reverse transcriptase-targeting therapies in various subtypes.Viruses. 01/2014; 6(9):3535-3562.