Minority M184V variants detected in women after receiving 3TC/FTC and LPV/r-containing regimens in pregnancy
Polly Clayden, HIV i-Base
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.
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