Decreased emergence of HIV-1 drug resistance mutations in a cohort of Ugandan women initiating option B+ for PMTCT

Abstract

BackgroundSince 2012, WHO guidelines for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in resource-limited settings recommend the initiation of lifelong antiretroviral combination therapy (cART) for all pregnant HIV-1 positive women independent of CD4 count and WHO clinical stage (Option B+). However, long-term outcomes regarding development of drug resistance are lacking until now. Therefore, we analysed the emergence of drug resistance mutations (DRMs) in women initiating Option B+ in Fort Portal, Uganda, at 12 and 18 months postpartum (ppm).Methods and findings124 HIV-1 positive pregnant women were enrolled within antenatal care services in Fort Portal, Uganda. Blood samples were collected at the first visit prior starting Option B+ and postpartum at week six, month six, 12 and 18. Viral load was determined by real-time RT-PCR. An RT-PCR covering resistance associated positions in the protease and reverse transcriptase HIV-1 genomic region was performed. PCR-positive samples at 12/18 ppm and respective baseline samples were analysed by next generation sequencing regarding HIV-1 drug resistant variants including low-frequency variants. Furthermore, vertical transmission of HIV-1 was analysed. 49/124 (39.5%) women were included into the DRM analysis. Virological failure, defined as >1000 copies HIV-1 RNA/ml, was observed in three and seven women at 12 and 18 ppm, respectively. Sequences were obtained for three and six of these. In total, DRMs were detected in 3/49 (6.1%) women. Two women displayed dual-class resistance against all recommended first-line regimen drugs. Of 49 mother-infant-pairs no infant was HIV-1 positive at 12 or 18 ppm.ConclusionOur findings suggest that the WHO-recommended Option B+ for PMTCT is effective in a cohort of Ugandan HIV-1 positive pregnant women with regard to the low selection rate of DRMs and vertical transmission. Therefore, these results are encouraging for other countries considering the implementation of lifelong cART for all pregnant HIV-1 positive women.

Human immunodeficiency virus type 1 ((HIV-1) subtypes in the northwest region, Cameroon

“…However, these findings were similar to those obtained elsewhere by Vergne et al, [27] and Mbunkah et al , [28]. This high level of NRTIs mutations detected in this study could be associated with the shift from the use of monotherapy NNRTI to the use of HAART among HIV infected pregnant and breast feeding women in the prevention of mother to child transmission of HIV [29, 30]. The detected NRTIs, K219Q mutation is known to confer resistance to Zidovudine (AZT) or Stavudine (D4T) [28].…”

Increasing proportions of HIV-1 non-B subtypes and of NNRTI resistance between 2013 and 2016 in Germany: Results from the national molecular surveillance of new HIV-diagnoses

“…HIV-1 genotypes from the protease (PR) and reverse transcriptase (RT) genomic region (2013–2016) and the integrase (INT) genomic region (2014–2016) were generated according to the previously published protocols [ 20 , 21 ]. Since 2015, Sanger sequencing has been substituted by next generation sequencing (NGS) using the Illumina MiSeq platform as described previously [ 22 ]. After extensive evaluations, a 20% threshold for defining ambiguities was applied to the NGS generated sequences to maintain consistency ( S1 Text).The HIV-1 subtype was assigned by applying the REGA HIV Subtyping Tool (3.0) [ 23 ] and COMET HIV-1 (1.0) [ 24 ] to the pol -sequence.…”

Food insecurity, drug resistance and non-disclosure are associated with virologic non-suppression among HIV pregnant women on antiretroviral treatment

“…Among women with unsuppressed VL in our study, 65% had detectable resistance mutations, mainly to NNRTIs. Rates of drug resistance among women on Option B+ in SSA have ranged from 6% to 46% in smaller studies [ 4 , 5 ]. Our findings suggest a need for resistance testing among pregnant women receiving NNRTI regimens.…”