Abstract
Six weeks of zidovudine (ZDV) is recommended for postnatal prophylaxis of HIV-exposed infants, but combination antiretrovirals are indicated if HIV transmission risk is increased. We investigated the frequency and severity of adverse events (AE) in infants receiving multiple drug prophylaxis compared to ZDV alone. In this retrospective review of 148 HIV-exposed uninfected infants born between 1997–2009, we determined clinical and laboratory AE that occurred between days of life 8–42. Thirty-six infants received combination prophylaxis; among those, a three-drug regimen containing ZDV, lamivudine, and nevirapine was most common (53%). Rates of laboratory AE grade ≥1 were as follows for the combination prophylaxis and ZDV alone groups, respectively: neutropenia 55% and 39%; anemia 50% and 39%; thrombocytopenia 0 and 3%; elevated aspartate aminotransferase 3% and 3%; elevated alanine aminotransferase 0 and 1%; hyperbilirubinemia 19% and 42%. Anemia occurred more frequently in infants who received three-drug prophylaxis compared to infants who received ZDV alone (63% vs. 39%, p = 0.04); all anemia AE were grade 1 or 2 in the three-drug prophylaxis group. Overall, 75% of infants on combination prophylaxis and 66% of infants on ZDV alone developed grade ≥1 AE (p = 0.32), and 17% of infants in either group developed grade ≥3 AE. Stavudine was substituted for ZDV in 23 infants due to anemia or neutropenia. After this antiretroviral change, 50% of evaluable infants demonstrated improvement in AE grade, and 25% had no change. In conclusion, low grade anemia, neutropenia, and hyperbilirubinemia occurred frequently regardless of the prophylactic regimen, but serious AE were uncommon. Although most AE were typical of ZDV toxicity, the combination of ZDV with lamivudine and nevirapine resulted in an increased frequency of low-grade anemia. Further studies are needed to identify prophylactic regimens with less toxicity for infants born to HIV-infected mothers.
Highlights
Perinatal transmission of HIV has been reduced to less than 1% with use of antenatal, intrapartum, and postnatal antiretroviral prophylaxis (ARV) [1, 2]
The proportion of infants born preterm, a known risk factor for adverse events (AE), was not significantly different for those receiving combination ARV compared to ZDV alone [9/36 (25%) vs. 17/112 (15%), p = 0.21]
We found a slightly higher frequency of grade 2 anemia in our three-drug prophylaxis group than was noted in the three-drug prophylaxis group in the NICHD-HPTN 040/PACTG 1043 trial (32% vs 26%), possibly owing to the fact that the mothers in that study did not receive antenatal ARV, which likely has a cumulative effect upon infant laboratory AE [9]
Summary
Perinatal transmission of HIV has been reduced to less than 1% with use of antenatal, intrapartum, and postnatal antiretroviral prophylaxis (ARV) [1, 2]. For infants with increased transmission risk, such as those with absent or incomplete antenatal prophylaxis, or elevated maternal viral load at delivery, ZDV with the addition of three doses of nevirapine (NVP) in the first week of life is recommended [3]. The recent NICHD-HPTN 040/PACTG 1043 trial, which compared three postnatal prophylaxis regimens in infants who did not receive antenatal prophylaxis, found more neutropenia in infants who received ZDV, 3TC, and nelfinavir than in infants who received ZDV and three doses of NVP, or infants who received ZDV alone [9]. We report a low incidence of severe adverse events (AE) in HIV-exposed, uninfected infants who received either combination postnatal ARV or ZDV alone
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