Journal of Medical Virology 86:8–17 (2014) Polymorphisms in the HIV-1 gp41 env Gene, Natural Resistance to Enfuvirtide (T-20) and pol Resistance Among Pregnant Brazilian Women Mo ˆ nica Nogueira da Guarda Reis, Keila Correa de Alca ˆ ntara, Ludimila Paula Vaz Cardoso, and Mariane Martins Arau ´ jo Stefani* Tropical Pathology and Public Health Institute, Federal University of Goia´s, Goiaˆnia, Goia´s, Brazil The selective pressure of antiretroviral drugs (ARVs) targeting HIV-1 pol can promote drug resistance mutations in other genomic regions, such as env. Drug resistance among women should be monitored to avoid horizontal and mother-to-child transmission. To describe nat- ural resistance to T-20 (enfuvirtide), gp41 env polymorphisms, mutations in pol and HIV-1 subtypes, 124 pregnant women were recruited. For 98 patients, the gp41 env, protease (PR) and reverse transcriptase (RT) fragments were sequenced. The patients were ARV naı¨ve (n ¼ 30), taking mother-to-child transmission prophylaxis (n ¼ 50), or being treated with highly active ARV therapy/HAART (n ¼ 18). The Stanford and IAS/USA databases and other sources were used to analyze PR/RT, gp41 env resistance mutations. The HIV-1 genetic diver- sity was analyzed by REGA/phylogenetic analy- ses. The patients’ median age was 25 years (range, 16–42), 18.4% had AIDS. The frequency of natural resistance to T-20 (N42D, L44M, and R46M-low-impact mutations) was 6.1% (6/98); 20.4% (20/98) had compensatory mutations in HR2. The prevalence of transmitted drug resis- tance in the pol was 13.3% (4/30), and the prevalence of secondary drug resistance was 33.3% (6/18). Two patients were infected with multidrug resistant/MDR viruses. The analysis of HIV-1 subtypes (PR/RT/gp41) revealed that 61.2% (60/98) were subtype B, 12.2% (12/98) were subtype C, 4.1% (4/98) were subtype F1, and 22.4% (22/98) were possible recombinants (BF1 ¼ 20.4%; BC ¼ 2%). Natural resistance to T-20 was not associated with pol resistance or previous ARV use. The high rate of secondary resistance, including MDR, indicates that the number of women that may need T-20 salvage therapy may be higher than anticipated. J. Med. Virol. 86:8–17, 2014. # 2013 Wiley Periodicals, Inc. KEY WORDS: enfuvirtide; HIV-1 resistance; pregnant women; Central-West Region Brazil INTRODUCTION During the last two decades, the proportion of women infected with HIV-1 has grown significantly worldwide, and women now represent nearly half of the 34 million persons infected with HIV-1 [WHO/UNAIDS, 2006; WHO/UNAIDS, 2011]. In Brazil, the ratio of man to woman infected with HIV-1 has changed from 40:1 in 1983 to 1.7:1 in 2010 [Brazil, 2011]. In the context of the “feminization” of the AIDS epidemic, prenatal screening for HIV-1 infection has become an important public health issue and a unique opportunity to provide early diagnosis, treatment, and prevention of mother-to-child transmission of HIV-1. Grant sponsor: United Nations Educational Scientific and Cultural Organization (UNESCO) AIDS/STD National Program; Brazilian Ministry of Health; Grant number: 310-06.; Grant sponsor: MS/MCT/CNPq–SCTIE-DECIT/CT-Sau ´ de; Grant number: 022/2007.; Grant sponsor: Fundac ¸a ˜o de Amparo a ` Pesquisa do Estado de Goia ´s (FAPEG to K. C. Alca ˆ ntara); Grant number: 200910267000696.; Grant sponsor: FAPEG (to M. N. G. Reis); Grant number: 201210267000386.; Grant sponsor: Conselho Nacional de Desenvolvimento Cientı ´fico e Tecnolo gico (CNPq to L. P. Cardoso); Grant number: 141820/2006-3.; Grant sponsor: CNPq (to M. M. Stefani); Grant number: 310582/2011-3. The authors declare that there is no conflict of interest involving this manuscript.  Correspondence to: Mariane Martins de Arau ´ jo Stefani, Universidade Federal de Goia ´ s, Instituto de Patologia Tropical e Sau ´de Pu ´ blica, Rua 235 s/n Setor Universita ´rio, 74605-050 Goia ˆnia, Goia ´ s, Brasil. E-mail: mariane.stefani@pq.cnpq.br Accepted 20 July 2013 DOI 10.1002/jmv.23738 Published online 13 September 2013 in Wiley Online Library (wileyonlinelibrary.com).  C 2013 WILEY PERIODICALS, INC.