Initiation of antiretroviral treatment in women after delivery can induce multiclass drug resistance in breastfeeding HIV-infected infants

Abstract

Background: The World Health Organization currently recommends initiation of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected lactating women with CD4+ cell counts <350 cells/μL or stage 3 or 4 disease. We analyzed antiretroviral drug resistance in HIV-infected infants in the Post Exposure Prophylaxis of Infants trial whose mothers initiated HAART postpartum (with a regimen of nevirapine [NVP], stavudine, and lamivudine). Infants in the trial received single-dose NVP and a week of zidovudine (ZDV) at birth; some infants also received extended daily NVP prophylaxis, with or without extended ZDV prophylaxis.

Methods: We analyzed drug resistance in plasma samples collected from all HIV-infected infants whose mothers started HAART in the first postpartum year. Resistance testing was performed using the first plasma sample collected within 6 months after maternal HAART initiation. Categorical variables were compared by exact or trend tests; continuous variables were compared using rank-sum tests.

Results: Multiclass resistance (MCR) was detected in HIV from 11 (29.7%) of 37 infants. Infants were more likely to develop MCR infection if their mothers initiated HAART earlier in the postpartum period (by 14 weeks vs after 14 weeks and up to 6 months vs after 6 months, P = .0009), or if the mother was exclusively breastfeeding at the time of HAART initiation (exclusive breastfeeding vs mixed feeding vs no breastfeeding, P = .003).

Conclusions: Postpartum maternal HAART initiation was associated with acquisition of MCR in HIV-infected breastfeeding infants. The risk was higher among infants whose mothers initiated HAART closer to the time of delivery or were still exclusively breastfeeding when they first reported HAART use.

Figure 1.

Human immunodeficiency virus (HIV) genotyping results obtained for infants who acquired multiclass resistance (MCR). HIV genotyping results are shown for 11 infants who acquired MCR after their mothers started highly active antiretroviral therapy (HAART); test results from all available samples are shown. The top row indicates the PEPI-Malawi study visit. Shaded boxes indicate the study visit at which the mothers first reported that they were receiving HAART. Non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistance mutations are shown in plain text and nucleoside reverse transcriptase inhibitor (NRTI)-resistance mutations are shown in bold. Infant designations 1-11 correspond to the designations in Table 2. Wk: weeks; Mo: months; WT: wild type (no resistance mutations detected).

Figure 2.

Factors associated with multiclass resistance (MCR) in infants whose mothers started highly active antiretroviral therapy (HAART) postpartum. A, Panel A shows the proportion of infants with MCR whose mothers reported that they had started HAART by 14 weeks postpartum (by 14 wk), at 6 months postpartum (6 mo), or after 6 months postpartum (after 6 mo). The P value for the comparison of all three groups is shown (Cochran–Armitage trend test). B, Panel B shows the proportion of infants with MCR whose mothers reported that they were exclusively breastfeeding, providing mixed feeding, or not breastfeeding at the visit where they first reported that they were receiving HAART. The P value for the comparison of all three groups is shown (Cochran–Armitage trend test). BF, breastfeeding.