Combination Antiretroviral Treatment for Women Previously Treated Only in Pregnancy

Abstract

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 co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) Methods Non-pregnant women with plasma HIV-1 RNA of ≥ 500 copies/mL, previously cART- exposed for pMTCT only, were eligible if they were off ART for ≥ 24 weeks prior to 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 54 women were enrolled between 10/07 and 12/09; 52/54 completed 24 weeks of follow- up. Median baseline CD4+ T-cell count was 265/mm3 and baseline plasma HIV-1 RNA was 4.6 log10 copies/mL. 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 42/52 women or 81% (exact 95% CI: 68%–90%). There were no differences in response by country, by number or class of prior pMTCT exposures. While 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 re- treatment 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 non-adherence.

Factors Affecting Virological Outcome When First-Line Antiretroviral Therapy Is Reintroduced After Unplanned Interruption

“…Several other studies, notably by Vogler et al 12 and Touloumi et al, 13 which did not succeed in proving this association, had patients with different CD4 count characteristics from our study, where their average CD4 counts before treatment resumption was higher, ranging at 265 to 332 cell/mm 3 . 12,13 Patients in Vogler and Touloumi studies achieved virological response rate higher than our studies (81% and 86%). Vogler mentioned that baseline CD4 count was not associated with virological response but mentioned nonadherence as the main factor for failures.…”

“…There were 61% of patients with CD4 count <200 cell/mm 3 . Median previous ART duration was 12 There is no guideline concerning choice of antiretroviral therapy (ART) for HIV-infected patients after unplanned interruption, despite evidences that reintroduction of firstline ART may resulted in failure of control of viral load.…”

“…[8][9][10] Several studies used protease inhibitors (PIs) antiretroviral class, which is only used as second-line ART in Indonesia, 11,12 or the studies involved patients with history of planned interruptions. 8,[11][12][13] Other studies did not address tenofovir (TDF) as base nucleoside reverse transcriptase inhibitors (NRTIs), 14 while TDF is also the drug of choice for first-line ART in Indonesia. The outline of this study is to analyze factors that contribute to virological success in first-line ART reintroduction based on Indonesia ART regimen.…”

sierra-local: A lightweight standalone application for secure HIV-1 drug resistance prediction

“…Structuring our processing pipeline in this way means we cannot, from NucAmino, directly obtain the requisite level of information necessary to make our analyses and resistance predictions. Thus, we had to develop several extra methods in sierra-local to supplement the information found in the NucAmino results: [14,15]. Because the HIVdb HIV Subtyping Program is very simple and does not perform phylogenetic analysis or bootstrapping, its results may not be as accurate as more sophisticated systems more commonly used such as the Rega Institute HIV-1 Automated Subtyping Tool [4].…”

HIV and Pregnancy

“…Another study of 54 non-pregnant women previously treated with cART in pregnancy, who had no evidence of drug resistance by bulk population genotyping at a median of 22 months following their last delivery, and then restarted treatment with an EFV based regimen, had few virologic failures. All were in women who reported incomplete adherence [61].…”