NIH Study Finds Lower PrEP Drug Concentration In Pregnant Teens And Young Women

Press release

Monday March 9, 2020

Strict adherence to daily PrEP is especially important during pregnancy, the researchers conclude.

Among adolescent girls and young African women who took daily HIV pre-exposure prophylaxis (PrEP), levels of tenofovir, a PrEP drug, were more than 30% lower in pregnant women than in those who had recently given birth. All 40 study participants took PrEP under direct observation, confirming their near-perfect adherence. Levels of PrEP drugs were lower to a similar degree in pregnant adolescent girls and young African women compared to American men and non-pregnant and non-lactating women who took PrEP daily under direct observation in an earlier study. These results from the NIH-funded IMPAACT 2009 study were reported today at the Conference on Retroviruses and Opportunistic Infections (CROI).

However, study investigators suggest that daily PrEP can provide substantial protection to pregnant African adolescent girls and young women as part of a comprehensive HIV prevention program.

“Adolescent girls and young women in sub-Saharan Africa, including those who are pregnant or have recently given birth, urgently need safe, desirable and effective HIV prevention tools,” said Anthony S. Fauci, MD , director of the National Institute of Allergies. and infectious diseases (NIAID) at NIH. “While taking PrEP as directed daily is important for all who receive it, these new data suggest that daily PrEP adherence will be especially essential for pregnant adolescents and young women. More research is needed to determine the level of protection that daily PrEP can provide for this population. “

NIAID is a co-founder of IMPAACT 2009.

The significantly lower drug concentration found in the dried blood spots of pregnant African adolescent girls and young women in the study did not necessarily indicate lower PrEP effectiveness for this group, according to IMPAACT 2009 researchers. The response to any drug follows a curve which rises from zero as the dose increases until the curve reaches a plateau where a range of doses reaches a biological response sufficient to have the desired effect – in this cases, prevent HIV infection. Based on the available data, the study researchers believe that the concentration of the drug in target cells of pregnant adolescents and women who take PrEP daily will fall near this plateau. However, more research is needed to determine if this is the case.

During pregnancy, the kidneys remove drugs from the blood faster than at other times, and the level of red blood cells in the plasma decreases. These physiological changes help explain the lower concentration of the drug PrEP seen in the dried blood spots of pregnant study participants. One of the goals of IMPAACT 2009 was to determine how much lower the drug concentration in pregnant adolescents and young women would be.

In sub-Saharan Africa, adolescent girls and young women are the most affected by new HIV cases. Girls account for four in five new HIV cases among adolescents aged 15 to 19, and adolescent girls and women aged 15 to 24 are twice as likely to be living with HIV as men. In addition, the risk of contracting HIV more than doubled for this population during pregnancy and the six months following childbirth, also known as the postpartum period.

PrEP is a powerful HIV prevention strategy that could potentially protect adolescent girls and young pregnant and postpartum women from acquiring the virus. This is to take one daily oral tablet containing two anti-HIV medicines. Studies have shown that PrEP reduces the risk of contracting HIV through sex by over 90% in men and women when taken daily. Additional studies have shown that women need to take PrEP tablets six to seven days a week for drug concentrations to reach protective levels in the female genital tract.

In two large clinical trials of PrEP in African women, VOICE and Fem-PrEP, the daily dosing regimen did not meet the needs of the study participants and therefore the HIV prevention strategy did not work. Therefore, scientists are looking for ways to introduce PrEP to African women and support their drug uptake so that this HIV prevention tool is a desirable and effective option for them.

The results reported today are from the first phase of the IMPAACT 2009 NIH-funded clinical trial. The study is designed to assess whether adolescent girls and young pregnant and postpartum women in southern and eastern Africa are willing and able to consistently take daily PrEP when they are supported, and whether PrEP is without it. danger to them and their infants. Investigators hypothesize that pregnant and breastfeeding women may be motivated only to start PrEP and take it consistently to protect themselves and their babies. A recent review studies on the safety of PrEP in pregnant and breastfeeding women have concluded that the benefits clearly outweigh the potential risks.

In this first phase of the trial, investigators measured the concentration of tenofovir in the red blood cells of pregnant and postpartum adolescents and young women who were taking PrEP or almost daily under direct observation of a member of the body. study team for 12 weeks. This data will serve as a baseline to accurately determine whether study participants are taking PrEP daily during the second phase of the trial, if it is being conducted, and in future studies of this drug PrEP in similar populations.

The study team recruited 40 adolescent girls and young women aged 16 to 24 in Malawi, South Africa, Uganda and Zimbabwe. Half of the participants were 14-24 weeks pregnant and half had given birth 6-12 weeks prior to enrollment. With the intense support of highly trained and experienced study staff, the women and adolescents collectively took more than 99% of their required daily PrEP doses under direct observation. Observation was primarily in person and occasionally via live video call. This allowed investigators to reliably confirm an almost perfect adhesion. The drug PrEP used in the study contains two drugs, tenofovir and emtricitabine.

The study team collected blood samples from study participants every week by dabbing a drop of blood on filter paper, where it dried. Scientists then took a hole punch from each dried blood spot and measured the tenofovir concentration in it. The researchers found that the median steady-state concentration of tenofovir was 965 femtomoles (fmol) per punch during pregnancy and 1,406 fmol / punch postpartum, a difference of 31%. Using a model that estimates how quickly tenofovir is cleared from the blood for each participant, the predicted median steady-state tenofovir concentrations were similar: 890 fmol / punch during pregnancy and 1418 fmol / punch postpartum. , a difference of 37%.

IMPAACT 2009 is sponsored and funded by NIAID, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all of which are part of the NIH. The study is being conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network under the direction of protocol co-chairs Benjamin Chi, MD, M.Sc., and Lynda Stranix-Chibanda, MBCh.B., M.Med . Dr Chi is Professor of Global Women’s Health in the Department of Obstetrics and Gynecology and the Department of Epidemiology at the University of North Carolina at Chapel Hill. Dr Stranix-Chibanda is a pediatrician and part-time lecturer at the College of Health Sciences, University of Zimbabwe in Harare. Gilead Sciences, Inc. donates PrEP drugs for the trial.

The first phase of IMPAACT 2009 was led by Peter Anderson, Pharm.D., Director of the Graduate Program in Pharmaceutical Sciences and Professor in the Department of Pharmaceutical Sciences at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of Colorado to Aurora.

More information on IMPAACT 2009 is available at ClinicalTrials.gov identifier under study NCT03386578.

NIAID conducts and supports research – at the NIH, in the United States, and around the world – to study the causes of infectious and immune-mediated diseases and to develop better ways to prevent, diagnose, and treat these diseases. Press releases, fact sheets and other materials related to NIAID are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the principal federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH… Transforming Discovery into Health®

Reference

P Anderson, et al. TFV-DP in DBS for pregnant / postpartum adolescents and young women on PrEP in Africa. Conference on retroviruses and opportunistic infections. Presented March 9, 2020.

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