Primary and secondary antiretroviral resistance mutations among HIV-1 infected pregnant women from Central West Brazil
J. Bacelar Acioli Lins, K. Correia Alcantara, L. Vaz Cardoso, M. Guarda Reis, A. Augusto Silveira, M. Martins de Araujo Stefani
Federal University of Goias, Immunology, Goiania, Brazil
Background: Antiretroviral (ARV) drug therapy (nucleoside reverse transcriptase inhibitors, NRTI; nonnucleoside reverse transcriptase inhibitors, NNRTI; protease inhibitors, PI) during pregnancy can prevent HIV-1 mother-to-child transmission (MTCT). However, drug resistance mutations may reduce the efficacy of therapy increasing the risk of MTCT.
Objectives: To assess ARV resistance mutations among HIV-1 infected pregnant women.
Methods: Patiens recruited in Goiás State, central west Brazil (2008-2009) had viral loads, CD4 counts assessed. Protease/PR and partial Reverse Transcriptase/RT genes were PCR-amplified and sequenced from plasma RNA. ARV mutations in PR/RT were analyzed by the Stanford Database/International AIDS Society-USA list.
Results: Main features of 94 pregnant women were: median age =26 years (16-42 range), 57% (54/94) were recently diagnosed (21 weeks median gestational age); 38% were AIDS cases, 67% were ARV-naïve; 19% (18/94) were under ARV and 14% discontinued ARV. Seventy samples were genotyped, 24 were not PCR-amplified. Among naïve women 5.7% (3/53) had primary drug resistance mutations: PI mutations M46I (n=1) and NNRTI mutations K103N, M230L (n=2). Secondary drug resistance was observed in 35.3% (6/17) of ARV-experienced patients, 2 had major mutations to three ARV classes. Major PI mutations- D30N, M46L, I50L, V82A, N88D, L90M (n=3); intermediate/high NNRTI resistance mutations- L100I, K101E, K103N, Y181C, G190A, P225H (n=5); NRTI mutations- D67N/G, K70R, M184V, T215Y and K219E (n=4) were observed. Resistance mutations to nevirapine, lamivudine and zidovudine prevailed among multidrug experienced women: 4/6 were on HAART (zidovudine/lamivudine/lopinavir) and 2 discontinued medication. Medians of viral loads and CD4+T cell counts of ARV-experienced women were 9,646 copies/mL and 387 CD4+cells/mL.
Conclusions: Moderate level of primary and high level of secondary ARV resistance mutations were observed among HIV-1 infected pregnant women. Among ARV experienced group, the high frequency of resistance mutations to zidovudine/lamivudine, the most used NRTI combination for MTCT prophylaxis in Brazil, raises concerns.
FUNDING: UNESCO/AIDS/STD/Brazilian Ministry of Health (Grant#310-06). MS/MCT/CNPq/SCTIE/DECIT/CT-Saúde (GRANT #022/2007).
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