Minority M184V variants detected in women after receiving 3TC/FTC and LPV/r-containing regimens in pregnancy

Short-term antiretroviral therapy (START) of two NRTIs and a ritonavir boosted PI is used frequently to prevent mother to child transmission in the UK. Resistance is rarely detected using standard genotyping following this strategy.

Sabrina Surah and colleagues conducted a multicentre study to determine whether minority M184V variants emerge with 3TC/FTC and LPV/r containing START regimens in pregnancy, and, if so, whether this has an impact on future treatment success.

The investigators used an allele-specific real time PCR (ASPCR), optimised for subtypes B, C and AG, to detect minority M184V variants. This assay has a lower limit of detection of 0.5%.

Plasma samples were tested pre and post treatment and routine population based sequencing (Viroseq) was also performed.

Samples from 38 women were tested and ASPCR failed in 15 (39%). Of the remaining 23 women, 16 (42%) had wild type (WT) virus and 7 (18%) had minority M184V sequences with a range of detection between 0.5% and 14%. The investigators noted that all samples were WT with population-based sequencing.

ASPCR failed to amplify from pre- treatment samples in 4/7 women with minority M184V and was WT in 3. Therapeutic drug monitoring of lopinavir was performed in a subset of women.

The investigators found no difference in prior ART, duration of START, drug concentration of LPV/r or virological suppression with subsequent ART in women with or without mutations. There were more women with subtype C among those with M184V mutations, 5/7 (62%) than those with WT, 1/16 (6%).

The investigators suggested that the possible association with HIV-1 subtype C requires further evaluation and a clade effect on acquisition of resistance has been reported following nevirapine use in pregnancy.

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That there was no difference in subsequent virological suppression between women with minority M184V mutations after START regimens is reassuring.

Surah S et al.: Minority M184V variants in women exposed to 3TC/FTC-containing lopinavir-ritonavir (LPVr) regimens in pregnancy. 10th International Congress on Drug Therapy in HIV Infection, November 7-11. Glasgow. Poster 159. Published in Journal of the International AIDS Society 2010 13(Suppl4):P159. http://www.jiasociety.org/content/13/S4/P159