Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.

Treatment response and drug resistance in patients infected with HIV type 1 group O viruses.

Information about the efficacy of antiretroviral drugs in HIV-1 group O strains as well on the virus evolution in terms of resistance development in vivo is very limited. We assessed the clinical, immunological, and virological response to antiretroviral therapy as well as the selection of drug resistance in six HIV-1 group O-infected patients. All but one initiated antiretroviral therapy with two nucleoside reverse transcriptase inhibitors (NRTI) plus one protease inhibitor (PI). At baseline, median plasma HIV-1 group O RNA and CD4 counts were 32,256 (15,770-74,132) copies/ml and 88 cells/microl (13-170), respectively. Four patients reached undetectable plasma viremia 12 weeks after beginning treatment. However, viremia rebounded in one of them due to poor compliance. Another two patients had an initial reduction in plasma HIV-RNA greater than 1 log, but rebounded soon thereafter. At baseline, all patients' viruses revealed changes associated with NNRTI resistance (98G and 181C). Two out of three patients failing therapy developed resistance mutations. One selected changes M41L, E44D, D67N, V75M, M184V, and T215Y at the RT, and G48M, F53L, I54V, V82A, and L90M at the protease. Another selected mutations K70N, V75A, and M184V at the RT, and D30D/N and I84V at the protease while failing on indinavir. Interestingly, both patients showed a shift at codon 181 from C to Y, which might restore NNRTI susceptibility. Sustained viral suppression in HIV-1 group O-infected patients can be successfully achieved using antiretroviral regimens based on two NRTI and a boosted PI. Drug resistance mutations in HIV-1 group O seem to be selected at similar positions to those in HIV-1 group M viruses.