In Utero NRTI Exposure and Mitochondrial Dysfunction: How Much Should We Worry?

Several reports indicate that mitochondrial dysfunction might occur in HIV-negative infants with in utero exposure to NRTIs, but the evidence is inconsistent. To evaluate this issue further, researchers studied 1037 HIV-negative children who were born to HIV-positive mothers between 1991 and 2002 and who were enrolled in PACTG 219/219C. Neuropsychological testing was performed every 6 months until age 2 or 3 and annually thereafter.

Twenty of the children (1.9%) met strict criteria for clinical manifestations suggestive of mitochondrial dysfunction. Overall, in utero NRTI exposure (all NRTIs or a specific NRTI) was not associated with possible mitochondrial dysfunction. In fact, 3 (15%) of the 20 babies with possible mitochondrial dysfunction — and 101 (10%) of the 1017 without — had no in utero antiretroviral exposure. However, babies with possible mitochondrial dysfunction were significantly more likely to have had first exposure to 3TC or AZT/3TC during the third trimester. They were also more likely to be male and to have been born in earlier calendar years. Babies with and without possible mitochondrial dysfunction did not differ significantly with respect to race, birth weight, prematurity, receipt of antiretroviral prophylaxis as neonates, median peak maternal viral load during the third trimester or at delivery, or in utero exposure to tobacco, alcohol, or psychoactive drugs. However, information on maternal viral load and in utero drug exposure was unavailable for 37% and 24% of infants, respectively.