Background:  Nevirapine (NVP) monotherapy appears highly efficacious in preventing mother-to-child transmission (PMTCT) of HIV-1. Unfortunately, NVP-based PMTCT results in NVP resistance. Women starting highly active anti-retroviral therapy (HAART) soon after NVP-based PMTCT may have more virologic failure than NVP-naïve individuals. Long-term outcome data are not yet available.

Methods:  We performed stochastic simulations of 20 years of follow-up in cohorts of 10,000 pregnant sub-Saharan African women under 4 scenarios. We modeled single-dose NVP (SD-NVP) PMTCT with 100, 50, and 10% subsequent access to HAART in eligible women. We compared these scenarios to HAART-based PMTCT (all women receive HAART during pregnancy and 6 months’ lactation) with 100% subsequent HAART access. Model parameters were based on published and unpublished data, preferentially from African populations, and reviewed by clinical HIV experts. We assumed that NVP monotherapy doubled risks of both initial failure of HAART to suppress HIV, and of virologic failure among those who suppressed. Sensitivity analysis was performed for key parameters.

Results:  Simulations predict that with 100% access to HAART, the effect of NVP resistance on long-term survival is small. Survival with SD-NVP and 100% HAART compared favorably with survival with HAART-based PMTCT at both 5 years (58 vs 60%) and 10 years (37 vs 41%). Predicted excess mortality due to NVP resistance is ~2% per 5 years. The effect of HAART access appears more substantial: in the SD-NVP scenarios, 10-year survival among populations with 10, 50, and 100% access to HAART was 6, 21, and 37%.

Conclusions:  Our model suggests that the effect of NVP resistance on mortality may not be apparent for many years; and, once it appears, may be small. Current forecasts, based on short-term follow-up of PMTCT programs involving initiation of HAART < 2 years post-delivery, may exaggerate the influence of NVP resistance on survival. Two main factors may explain our results. First, HIV-infected pregnant women are fairly healthy, with relatively high CD4 counts. Second, HAART can have a sustained effect on survival, even after HAART failure. The long-term effects of NVP resistance on survival appear minor compared with the effects of less-than-universal access to HAART. It follows that concerns about NVP resistance should not slow roll-out of non-HAART PMTCT, and that wide access to HAART will have vast public health benefits in the developing world.

Keywords: Prevention of mother to child transmission (PMTCT); Nevirapine resistance; Stochastic modeling