6 research outputs found
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Predictors of Viremia in Postpartum Women on Antiretroviral Therapy.
BackgroundHIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study.MethodsWomen with pre-ART CD4 T-cell counts â„400 cells/mm who started ART during pregnancy were randomized postpartum to continue ART (CTART) or discontinue ART (DCART). Viral load and self-reported adherence were collected every 12 weeks, up to 144 weeks. Women in DCART reinitiated therapy when clinically indicated. Viremia was defined as 2 consecutive viral loads >1000 copies/mL after 24 weeks on ART. Adherence was dichotomized as missing versus not missing ART doses in the past 4 weeks. Predictors of viremia were examined using Cox proportional hazards regression with adherence as a time-varying covariate.ResultsAmong 802 women in the CTART arm, median age at entry was 27 years and median CD4 T-cell count 696 cells/mm. Of 175 women in CTART with viremia (22%), 141 had resistance data, and 12% had resistance to their current regimen. There was an estimated 0.12 probability of viremia by week 48 and 0.25 by week 144. Predictors of viremia included missed ART doses within the past 4 weeks, younger age, shorter duration of pre-entry ART, and being from the South American/Caribbean region. Of 137 women in DCART who reinitiated therapy, probability of viremia was similar to CTART (0.24 by week 96; 0.27 by week 144).ConclusionsRates of postpartum viremia are high and viremia is more likely in younger postpartum women who start ART later in pregnancy. Interventions should target these higher-risk women
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Slow acceptance of universal antiretroviral therapy (ART) among mothers enrolled in IMPAACT PROMISE studies across the globe
CITATION: StranixâChibanda, L., et al. 2019. Slow acceptance of universal antiretroviral therapy (ART) among mothers enrolled in IMPAACT PROMISE studies across the globe. AIDS and Behavior, 23:2522-2531, doi:10.1007/s10461-019-02624-3.The original publication is available at https://link.springer.comThe PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the âTreat Allâ strategy.https://link.springer.com/article/10.1007/s10461-019-02624-3Publisher's versio
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Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy
BackgroundAdverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting.MethodsHuman immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts â„400 cells/ÎŒL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm.ResultsSubsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/ÎŒL (IQR, 492-833 cells/ÎŒL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4]).ConclusionsWomen randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens
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Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1â2 trial
BackgroundSafe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children.MethodsInternational Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir. A 5 mg dispersible tablet formulation of dolutegravir was studied in children aged 4 weeks to less than 6 years old, weighing at least 3 kg, with HIV RNA of greater than 1000 copies per mL and no previous treatment with integrase strand transfer inhibitor recruited from IMPAACT clinical research sites in Africa, the Americas, and Asia. Doses were selected on the basis of intensive pharmacokinetic evaluation on days 5-10, with safety and tolerability assessed up to 48 weeks. The primary objectives of this study are to evaluate the pharmacokinetics of dolutegravir in combination with optimised background therapy and to establish the dose of dolutegravir that achieves the targeted 24-h trough concentration and 24-h area under the curve for infants, children, and adolescents with HIV-1, to establish the safety and tolerability of dolutegravir at 24 and 48 weeks, and to select a dose that achieves similar exposure to the dolutegravir 50 mg once daily dose in adults. This analysis included participants treated with the proposed dose of dolutegravir dispersible tablets in two stages for each of three age cohorts. This trial is registered at ClinicalTrials.gov (NCT01302847) and is ongoing.FindingsWe recruited 181 participants from April 20, 2011, to Feb 19, 2020; of these, 96 received dolutegravir dispersible tablets. This analysis included 73 (35, 48% female) participants who received the final proposed dose with median (range) age of 1 year (0·1 to 6·0), weight (minimum-maximum) of 8·5 kg (3·7 to 18·5), plasma HIV-1 RNA concentration of 4·2 log10 copies per mL (2·1 to 7·0), and CD4% of 24·0% (0·3 to 49·0); 64 (87·7%) were treatment-experienced. The selected dose within each age cohort (â„2 years to <6 years, â„6 months to <2 years of age and â„4 weeks to <6 months) achieved geometric mean trough (ng/mL) of 688, 1179, and 1446, and 24 h area-under-the-curve (h·mg/L) of 53, 74, and 65, respectively. No grade 3 or worse adverse events were attributed to dolutegravir.InterpretationIn this study, the proposed once daily dosing of dolutegravir dispersible tablets provided drug exposures similar to those for adults, and was safe and well tolerated. These data support the use of dolutegravir dispersible tablets as first-line or second-line treatment for infants and children aged less than 6 years living with HIV-1.FundingNational Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Mental Health, and ViiV Healthcare-GlaxoSmithKline
Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial
Meeting abstract FRAB0101LB from 21st International AIDS Conference 18â22 July 2016, Durban, South Africa.
Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIVâinfected adults and children with advanced disease in subâSaharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown.
Methods:
The REALITY 2Ă2Ă2 factorial openâlabel trial (ISRCTN43622374) randomized ARTânaĂŻve HIVâinfected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (antiâtuberculosis) and fluconazole (antiâcryptococcal/candida), 5 days azithromycin (antiâbacterial/protozoal) and singleâdose albendazole (antiâhelminth)), versus standardâofâcare cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixedâdose combination. Two other randomizations investigated 12âweek adjunctive raltegravir or supplementary food. The primary endpoint was 24âweek mortality.
Results:
1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% lossâtoâfollowâup). Median baseline CD4 was 36 cells/mm3 (IQR: 16â62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54â0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58â0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2).
Conclusions:
Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIVâinfected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this lowâcost broad infection prevention package which could save 3.3 lives for every 100 individuals treated