Combination antiretroviral treatment for women previously treated only in pregnancy: week 24 results of AIDS clinical trials group protocol a5227.
BACKGROUND
Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF).


METHODS
Nonpregnant women with plasma HIV-1 RNA of ≥500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for ≥24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks.


RESULTS
Fifty-four women were enrolled between October 2007 and December 2009; 52 of 54 completed 24 weeks of follow-up. Median baseline CD4 T-cell count was 265/mm and baseline plasma HIV-1 RNA was 4.6 log10 copies per milliliter. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42 of 52 women or 81% (exact 95% confidence interval: 68% to 90%). There were no differences in response by country, by number, or class of prior pMTCT exposures. Although confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence.


CONCLUSIONS
In this first prospective clinical trial studying combination antiretroviral retreatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported nonadherence.
*Weill Cornell Medical College of Cornell University, New York Presbyterian Hospital, New York, NY; †Center for Biostatistics and AIDS Research, Harvard School of Public Health, Boston, MA; ‡Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY; §STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; ‖Asociación Civil IMPACTA Salud y Educación, Lima, Perú; ¶Social and Scientific Systems, Inc, Silver Spring, MD; #HIV Research Branch, Division of AIDS, National Institute of Allergy and Infectious Disease, National Institute of Health, Bethesda, MD; **University of Rochester School of Medicine and Dentistry, Rochester, NY; and ††Birmingham Veterans Affairs Medical Center and University of Alabama at Birmingham School of Medicine, Birmingham, AL.
Mary A
MA
Vogler
Laura M
LM
Smeaton
Rodney L
RL
Wright
Sandra W
SW
Cardoso
Jorge
J
Sanchez
Rosa
R
Infante
Laura E
LE
Moran
Catherine
C
Godfrey
Lisa M
LM
Demeter
Victoria A
VA
Johnson
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D063065:Organophosphonates / Q000627:therapeutic use; D011247:Pregnancy; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz