Primary HIV prevention in pregnant and lactating Ugandan women: A randomized trial.
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ABSTRACT:
SUBMITTER: Homsy J
PROVIDER: S-EPMC6388930 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Primary HIV prevention in pregnant and lactating Ugandan women: A randomized trial.
Homsy Jaco J King Rachel R Bannink Femke F Namukwaya Zikulah Z Vittinghof Eric E Amone Alexander A Ojok Francis F Rukundo Gordon G Amama Sharon S Etima Juliane J Matovu Joyce J Weissglas Fitti F Ojom Lawrence L Atim Pamela P Darbes Lynae L Byamugisha Josaphat J Rutherford George G Katabira Elly E Fowler Mary Glenn MG
PloS one 20190225 2
<h4>Background</h4>The 'Primary HIV Prevention among Pregnant and Lactating Ugandan Women' (PRIMAL) study aimed to assess the effectiveness of an enhanced HIV counseling intervention for preventing HIV acquisition among HIV-uninfected mothers during pregnancy and throughout the breastfeeding period.<h4>Methods</h4>We conducted an unblinded randomized control trial between 22 February 2013 and 22 April 2016 to assess the effectiveness of an extended repeat HIV testing and enhanced counseling (ERH ...[more]
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Project description:IntroductionSecondary distribution of HIV self-tests (HIVST) by HIV-negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV).MethodsWe conducted an open-label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard-of-care (SOC; invitation letter to male partner for fast-track testing). Women were followed until 12 months post-partum. Male partners were offered confirmatory HIV testing and facilitated linkage to antiretroviral treatment (ART) or oral pre-exposure prophylaxis (PrEP). Using intention-to-treat analysis, primary outcomes were male partner testing at the clinic and initiation on PrEP or ART evaluated through 12 months post-partum (ClinicalTrials.gov, NCT03484533).ResultsFrom November 2018 to March 2020, 500 PWLHIV were enrolled with a median age of 27 years (interquartile range [IQR] 23-30); 332 were randomized to HIVST and 168 to SOC with 437 PWLHIV (87.4%) completing 12 months follow-up post-partum. Of 236 male partners who tested at the clinic and enrolled (47.2%), their median age was 31 years (IQR 27-36), 45 (88.3%) men with HIV started ART and 113 (61.1%) HIV-negative men started PrEP. There was no intervention effect on male partner testing (hazard ratio [HR] 1.04; 95% confidence interval [CI]: 0.79-1.37) or time to ART or PrEP initiation (HR 0.96; 95% CI: 0.69-1.33). Two male partners and two infants acquired HIV for an incidence of 0.99 per 100 person-years (95% CI: 0.12-3.58) and 1.46 per 100 person-years (95% CI: 0.18%-5.28%), respectively. Social harms related to study participation were experienced by six women (HIVST = 5, SOC = 1).ConclusionsAlmost half of the partners of Ugandan PWLHIV tested for HIV with similar HIV testing rates and linkage to ART or PrEP among the secondary distribution of HIVST and SOC arms. Although half of men became aware of their HIV serostatus and linked to services, additional strategies to reach male partners of women in antenatal care are needed to increase HIV testing and linkage to services among men.
| S-EPMC10483500 | biostudies-literature
Project description:Introduction: Tenofovir alafenamide (TAF)-containing fixed-dose drug combinations (FDCs) are increasingly being used in managing pregnant women living with HIV. However, TAF is not currently recommended during pregnancy due to limited pharmacokinetic and safety data. TAF, a newer nucleotide phosphonamidate prodrug of tenofovir (TFV), achieves high levels of tenofovir-diphosphate in lymphoid cells and hepatocytes, and 90% lower systemic concentrations of TFV compared to tenofovir disoproxil fumarate (TDF), thereby maximizing TAF's antiviral efficacy, potency and clinical safety.Areas covered: This review discusses the currently available information on the pharmacology of TAF in pregnant women living with HIV. Pharmacokinetic studies with TAF during pregnancy have yielded varying results compared to postpartum, but TAF exposures during pregnancy have been within the range of those typically observed in non-pregnant adults. The efficacy and safety of TAF in treatment-naïve pregnant women living with HIV is currently being evaluated in the VESTED study, a phase-III NIH randomized clinical trial.Expert opinion: Initial pregnancy data suggest that TAF-based FDCs have high efficacy and low risk of adverse effects during pregnancy. TAF is likely to become part of first-line regimens for use in pregnant women living with HIV once additional pregnancy data from phase III trials are available.
| S-EPMC9214649 | biostudies-literature
Project description:BackgroundNipple pain and damage in breastfeeding mothers are common causes of premature breastfeeding cessation. Peppermint water is popularly used for the prevention of nipple cracks in the North West of Iran. The aim of this study was to determine the effectiveness of peppermint water in the prevention of nipple cracks during breastfeeding in comparison with the application of expressed breast milk (EBM).MethodsOne hundred and ninety-six primiparous breastfeeding women who gave birth between February and May 2005 in a teaching hospital in Tabriz, Iran, were randomized to receive either peppermint water or EBM. Each woman was followed for up to three visits or telephone calls within 14 days and then by telephone call at week six postpartum.ResultsWomen who were randomized to receive peppermint water were less likely to experience nipple and areola cracks (9%) compared to women using EBM (27%; p < 0.01). Women who used the peppermint water on a daily basis were less likely to have a cracked nipple than women who did not use peppermint water (relative risk 3.6, 95%CI: 2.9, 4.3). Nipple pain in the peppermint water group was lower than the expressed breast milk group (OR 5.6, 95% CI: 2.2, 14.6; p < 0.005).ConclusionThis study suggests that peppermint water is effective in the prevention of nipple pain and damage. Further studies are needed to assess the usefulness of peppermint water in conjunction with correct breastfeeding techniques.
| S-EPMC1865372 | biostudies-literature
Project description:BACKGROUND:Protease inhibitor-based antiretroviral therapy (ART) has been associated with preterm birth in some studies. We examined risk factors for preterm birth among women randomized to lopinavir/ritonavir (LPV/r)- or efavirenz (EFV)-based ART. METHODS:This was a planned secondary analysis of the PROMOTE-Pregnant Women and Infants Study, an open-label, randomized controlled trial comparing the risk of placental malaria among HIV-infected, ART-naive pregnant Ugandan women assigned to initiate LPV/r- or EFV-based ART at 12-28 weeks gestation. Gestational age was determined based on last menstrual period and ultrasound biometry. All women received bednets and trimethoprim-sulfamethoxazole. Stillbirths, spontaneous abortions, and multiple gestations were excluded from the primary analysis. Potential risk factors for preterm birth (<37 weeks gestation) were evaluated by univariate and multivariate logistic regression. RESULTS:Three hundred fifty-six women were included in this analysis. At enrollment, median gestational age was 21 weeks and median CD4 cell count was 368 cells per cubic millimeter. 14.7% of deliveries in the EFV arm and 16.2% in the LPV/r arm were preterm. Preterm birth was associated with gestational weight gain below 0.1 kg/week versus 0.1 kg/week or more [odds ratio (OR) = 2.49; 95% confidence interval (CI): 1.38 to 4.47; P = 0.003]. Neither ART regimen of LPV/r versus EFV (OR = 1.12; 95% CI: 0.63 to 2.00; P = 0.69) nor placental malaria (OR = 0.74; 95% CI: 0.38 to 1.44; P = 0.37) was associated with preterm birth. CONCLUSIONS:LPV/r was not associated with an increased risk of preterm birth compared with EFV. However, interventions are needed to address modifiable risk factors for preterm birth, such as nutritional status (ClinicalTrials.gov, NCT00993031).
| S-EPMC4414017 | biostudies-literature
Project description:Hair concentrations are a noninvasive measure of cumulative antiretroviral exposure and the strongest predictor of viral suppression in large cohorts of nonpregnant patients. We examined hair concentrations of antiretrovirals in relation to virologic outcomes in pregnant and breastfeeding women for the first time.The Prevention of Malaria and HIV Disease in Tororo trial (NCT00993031) enrolled HIV-infected pregnant Ugandan women at 12-28 weeks gestation who were randomized to lopinavir or efavirenz-based antiretroviral therapy (ART). Small hair samples were collected at 30-34 weeks gestation and 10-25 weeks postpartum. Efavirenz and lopinavir hair concentrations were measured via liquid chromatography/tandem mass spectrometry. Multivariate logistic regression models examined predictors of viral suppression (HIV-1 RNA ?400?copies/ml) at delivery and 24 weeks postpartum.Among 325 women, median CD4 cell count was 366?cells/?l (interquartile range 270-488) at ART initiation. Mean self-reported 3-day adherence was greater than 97% in each arm. Viral suppression was achieved by 98.0% (efavirenz) and 87.4% (lopinavir) at delivery. At 24 weeks postpartum, 92.5% (efavirenz) and 90.6% (lopinavir) achieved viral suppression; 88% of women were breastfeeding. In multivariate models including self-reported adherence and pretreatment HIV-1 RNA, antiretroviral hair concentrations were the strongest predictor of viral suppression at delivery [efavirenz: adjusted odds ratio (aOR) 1.86 per doubling in concentration, 95% confidence interval (CI) 1.14-3.1, P?=?0.013; lopinavir: aOR 1.90, 95% CI 1.33-2.7, P?=?0.0004] and 24 weeks postpartum (efavirenz: aOR 1.81, 95% CI 1.22-2.7, P?=?0.003; lopinavir: aOR 1.53, 95% CI 1.05-2.2, P?=?0.026).Antiretroviral hair concentrations represent an innovative tool that strongly predicts viral suppression among HIV-infected childbearing women during the critical periods of delivery and breastfeeding.
| S-EPMC4438773 | biostudies-literature
Project description:Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)-convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low-income and middle-income countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical.
| S-EPMC8167886 | biostudies-literature
Project description:ObjectiveCombination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4⁺ cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda.DesignRandomized clinical trial.MethodsWe performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naive pregnant women at 12-28 weeks gestation and any CD4⁺ cell count were randomized. ART was provided and participants were counseled to breastfeed for 1 year postpartum.ResultsThe median age of the 389 study participants was 29 years; median CD4⁺ cell count was 370 cells/μl. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm (P < 0.001). At 48 weeks postpartum, 91.0% of women on efavirenz and 88.4% on lopinavir/ritonavir had viral suppression (P = 0.49). Grade 1 or 2 gastrointestinal adverse events were higher among women on lopinavir/ritonavir versus efavirenz. Only two infants acquired HIV (both in the lopinavir/ritonavir arm), and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz) (P = 0.10).ConclusionVirologic suppression at delivery was higher with an efavirenz versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through 1 year postpartum and the risk of transmission to infants was low.
| S-EPMC4428759 | biostudies-literature
Project description:Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications.To describe and analyze the major ethical challenges faced in HPTN 052.The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described.When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV infection and AIDS. Furthermore, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV-prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the guidelines used at the sites where the research was being conducted. In addition, questions were raised about whether there was an obligation to notify subjects about 'unlinked' transmissions of HIV, that is, infections acquired from someone other than the designated sexual partner enrolled in the study.The ethical issues described are limited to those discerned by the authors and not those of other stakeholders who may have identified additional issues or had a different perspective in analyzing them.Understanding the ethical challenges faced in HPTN 052 promises to inform the design and conduct of future complex, long-term clinical trials aimed at addressing critical scientific and public health questions, where data and practice patterns emerge over the course of the trial.
| S-EPMC3486723 | biostudies-other
Project description:BackgroundDisclosure of Human Immune Virus (HIV) serostatus by pregnant and lactating women is crucial for the successful prevention of mother to child transmission of HIV/AIDS. However, little has been studied regarding the prevalence and factors associated with HIV status disclosure among HIV positive pregnant and lactating women in Ethiopia.MethodsAn institution-based cross-sectional study was conducted in the Nekemte Public Health facilities among 380 pregnant and lactating women enrolled in universal antiretroviral therapy (ART) treatment from January 2015-December, 2019. The data were collected by using a checklist, developed from Prevention of Mother to Child Transmission (PMTCT) logbook, ART intake forms, and medical cards of the patients. Epidata version 3.2 was used for data entry, and then the data were exported to STATA version 14 for further analysis. The binary logistic regression model was employed to determine factors associated with the disclosure status among HIV positive pregnant and lactating women. Adjusted Odds Ratio (AOR) with 95% confidence intervals was computed and statistical significance was declared when it is significant at a 5% level (p-value < 0.05).ResultsA total of 380 women have participated in the study. Two hundred seventy-six (73.4%) of women had disclosed their HIV status to at least one individual. The study found living in urban (OR = 1.83, 95% CI: 1.04, 3.20), married women (OR = 4.16, 95% CI: 1.87, 9.24), higher educational status (OR = 2.35, 95% CI: 1.31, 5.51), positive HIV status of partner (OR = 2.35, 95%CI: 1.17, 4.70), and being multipara (OR = 4.94, 95% CI: 2.29, 10.66) were independent determinants of HIV status disclosure.ConclusionsHIV status disclosure among pregnant and lactating women in the study area was sub-optimal. Empowering women through education, encouraging partners for HIV testing, and enhancing active male involvement in HIV treatment and control programs should get due attention.
| S-EPMC7978369 | biostudies-literature
Project description:ObjectiveTrimethoprim-sulfamethoxazole prophylaxis is recommended for HIV-exposed infants until breastfeeding ends and HIV infection has been excluded. Extending prophylaxis with a focus on preventing malaria may be beneficial in high transmission areas. We investigated three regimens for the prevention of malaria in young HIV-exposed children.DesignAn open-label, randomized controlled trial.SettingTororo, Uganda, a rural area with intense, year-round, malaria transmission.ParticipantsTwo hundred infants aged 4-5 months enrolled and 186 randomized after cessation of breastfeeding and confirmed to be HIV uninfected (median 10 months of age).InterventionNo chemoprevention, monthly sulfadoxine-pyrimethamine, daily trimethoprim-sulfamethoxazole or monthly dihydroartemisinin-piperaquine given from randomization to 24 months of age.Main outcome measuresThe primary outcome was the incidence of malaria during the intervention period. Secondary outcomes included the incidence of hospitalization, diarrhoeal illness, or respiratory tract infection; prevalence of anaemia and asymptomatic parasitemia; measures of safety; and incidence of malaria over 1 year after the intervention was stopped.ResultsDuring the intervention, the incidence of malaria in the no chemoprevention group was 6.28 episodes per person-year at risk. Protective efficacy was 69% [95% confidence interval (95% CI) 53-80, P < 0.001] for dihydroartemisinin-piperaquine, 49% (95% CI 23-66, P = 0.001) for trimethoprim-sulfamethoxazole and 9% for sulfadoxine-pyrimethamine (95% CI -35 to 38, P = 0.65). There were no significant differences in any secondary outcomes, with the exception of a lower prevalence of asymptomatic parasitemia in the dihydroartemisinin-piperaquine arm.ConclusionMonthly chemoprevention with dihydroartemisinin-piperaquine was well tolerated and associated with a significant reduction in malaria in young HIV-exposed children.
| S-EPMC4487368 | biostudies-literature