Breast‐Milk Shedding of Drug‐Resistant HIV‐1 Subtype C in Women Exposed to Single‐Dose Nevirapine

Abstract

Single-dose nevirapine reduces intrapartum human immunodeficiency virus 1 type (HIV-1) transmission but may also select for nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance in breast milk (BM) and plasma. Among 32 Zimbabwean women, median 8-week postpartum plasma and BM HIV-1 RNA levels were 4.57 and 2.13 log(10) copies/mL, respectively. BM samples from women with laboratory-diagnosed mastitis (defined as elevated BM Na(+) levels) were 5.4-fold more likely to have HIV-1 RNA levels above the median. BM RT sequences were not obtained for 12 women with BM HIV-1 RNA levels below the lower limit of detection of the assay used. In 20 paired BM and plasma samples, 65% of BM and 50% of plasma RT sequences had NNRTI-resistance mutations, with divergent mutation patterns.

Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

“…Our findings confirm previous studies reporting high frequencies of drug-resistant virus in breast milk of NVP-SD-exposed pregnant women infected with HIV-1 [13][14][15]. Additionally, we found that most of the detected resistance mutations were present as minor drug-resistant variants accounting for <5% of the total viral population.…”

“…Different mutation patterns in breast milk and plasma is a consistent finding [13,14,23]. Furthermore, HIV-1 mutation patterns can also differ between samples from the right and left breast of the same women [14]. While it has been shown that a short-course of combivir (zidovudine and lamivudine) over 1 week can prevent the formation of NVP resistances in plasma after NVP-SD intake [24], it is not known whether this holds true for other compartments, that is, for breast milk.…”

“…Lee et al [14] found drug-resistant virus in 65% of breast milk samples of women infected with HIV-1 subtype C 8 weeks after NVP-SD exposure using a population-based approach. Similarly, drug-resistant viruses in plasma have been shown to emerge at higher frequencies in subtype C as compared with subtype A and D [4,11], which also appears to be true for breast milk.…”

“…So far, only three studies have determined the emergence of NVP-resistant virus in breast milk following intake of NVP-SD. Two studies analysed breast milk of women infected with HIV-1 subtype C and showed that HIV-1 variants in breast milk emerged frequently and often differed in sequences from resistant HIV-1 variants in plasma [13,14]. Recently, a third study analysed breast milk samples of women mainly infected with HIV-1 subtypes A and D using a population-based approach with a detection limit for drug-resistant HIV-1 variants of approximately 20% [15].…”

HIV/AIDS epidemiology, pathogenesis, prevention, and treatment

“…143 Around half the women who received one dose of nevirapine to prevent mother-to-child transmission harbour viruses resistant to non-nucleoside reverse transcriptase inhibitors (NNRTI). 144,145 These resistant viruses replicate efficiently and can be transmitted by breast milk, 146 and minor resistant populations present long after the intervention can possibly decrease the effectiveness of subsequent NNRTI-based treatment regimens. 147 The combination of short-course zidovudine, lamivudine, and nevirapine prevents peripartum transmission while reducing the risk of nevirapine resistant viruses.…”