Objective: Antiretroviral therapy (ART) effectively prevents mother-to-child transmission of HIV (PMTCT), but a severe neurologic syndrome in the children may result from in utero ART exposure. Our objective was to quantify the effects of recommended PMTCT regimens on HIV transmission and neurologic toxicity (NT).

Methods: Using a decision analytic model of ART for PMTCT in developing countries, we investigated total cases of HIV and NT resulting from six different strategies: no ART; single-dose nevirapine (sdNVP); World Health Organization (WHO) 1st, 2nd, and 3rd-line recommendations; and 3-drug ART. Published HIV transmission risks (0.8-7.0% antepartum, 0.7-19.9% intrapartum, 0-18.2% postpartum) and neurologic toxicity risks (0.01- 2.0%) were used for each regimen. In sensitivity analysis, we created "worst case" scenarios for HIV and NT risks, examined the effects of formula-feeding, and varied the disability of NT relative to HIV infection.

Results: Total cases of HIV+NT range from a high of 34.6% with no ART to a low of 4.5% with 3-drug ART:

ART strategy (#  of toxic antepartum drugs)		HIV infection (%)	Neurologic toxicity (%)	HIV  + NT (%)
No ART	(0)	34.4	0.2	34.6
sdNVP	(0)	14.5	0.2	14.7
WHO 3rd-line	(0)	12.1	0.2	12.3
WHO 2nd-line	(1)	9.4	2.0	11.4
WHO 1st-line	(1)	9.1	2.0	11.1
3-drug ART	(2)	2.3	2.2	4.5

When "worst case" risks are true for both HIV and NT, WHO 1st- and 2nd-line strategies minimize total adverse outcomes compared to 3-drug ART. Formula-feeding does not change the ordering of the strategies with regard to total adverse outcomes. Only if disability from NT exceeds that of HIV infection by 4.8-fold, WHO 3rd-line ART (which excludes toxic antepartum drugs) minimizes total adverse outcomes.

Conclusions: The most effective PMTCT regimens also appear to increase risk for neurologic toxicity in exposed children. However, these regimens substantially decrease total adverse pediatric outcomes, unless neurologic toxicity is much more common than currently reported or more morbid than pediatric HIV infection. Three-drug ART should be used for PMTCT wherever possible.