Safety and tolerability of antiretrovirals during pregnancy.

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥ 3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.

Kinetics and determining factors of the virologic response to antiretrovirals during pregnancy.

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log(10) after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to >/=95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar characteristics.

Resistance to antiretrovirals in HIV-infected pregnant women.

BACKGROUND: Antiretrovirals suppress HIV replication and prevent mother-to-child-transmission of HIV (PMTCT). Resistance to antiretrovirals may reduce the efficacy of PMTCT and/or complicate treatment of maternal or infant infection. OBJECTIVES: To assess resistance to antiretrovirals during pregnancy. DESIGN: Retrospective chart review of 44 pregnancies. RESULTS: Twenty-two patients were antiretroviral treatment-naïve, 8 were on therapy, and 14 had prior therapy, but were off medication when the genotyping was performed. Major mutations were found in 10 antiretroviral-experienced women, including 5 women with major mutations to 2 classes of drugs (none to 3 classes). Major mutations were most common for lamivudine, nevirapine, zidovudine, stavudine, and abacavir. Three women had significant resistance to zidovudine/lamivudine, a combination recommended in PMTCT guidelines. Despite significant antiretroviral resistance, 6 of 8 women with plasma HIV RNA measured within 4 weeks of delivery achieved <50 copies/mL. All neonates were uninfected. Among 6 women who received antiretrovirals exclusively for PMTCT, there were no remarkable changes of the HIV genotype before and after pregnancy. CONCLUSIONS: Resistance to antiretrovirals was common in antiretroviral-experienced pregnant women, but not in naïve women. The 14% prevalence of resistance to zidovudine and lamivudine in antiretroviral-experienced women suggests that alternative NRTI are desirable for this group of patients.