Getting pregnant in HIV clinical trials: women’s choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials

Serris, Alexandra; Zoungrana, Jacques; Diallo, Mamadou Hassimiou; Toby, Roselyne; Ngolle, M.; Gac, Sylvie Le; Coutherut, J.; Cournil, Amandine; Beaudrap, Pierre De; Koulla‐Shiro, Sinata; Delaporte, Eric; Ciaffi, Laura

doi:10.1080/15284336.2016.1248624

Cited by 4 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To complement these approaches, well-designed, postlicensure pregnancy registries that can identify rare events not identified in clinical trials and allow for well-controlled causality assessments are needed, particularly in sub-Saharan Africa where HIV prevalence is high and pharmacovigilance efforts are nascent but urgently needed for HIV prevention and other interventions such as vaccines. 47…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

HIV Incidence Among Pregnant and Nonpregnant Women in the FACTS-001 Trial: Implications for HIV Prevention, Especially PrEP Use

Rees

Chersich

Munthali

et al. 2021

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

Background: During pregnancy and postpartum period, the sexual behaviors of women and their partners change in ways that may either increase or reduce HIV risks. Pregnant women are a priority population for reducing both horizontal and vertical HIV transmission.Setting: Nine sites in 4 South African provinces.Methods: Women aged 18-30 years were randomized to receive pericoital tenofovir 1% gel or placebo gel and required to use reliable modern contraception. We compared HIV incidence in women before, during, and after pregnancy and used multivariate Cox Proportional hazards models to compare HIV incidence by pregnancy status.Results: Rates of pregnancy were 7.1 per 100 woman-years (95% confidence interval [CI]: 6.3 to 8.1) and highest in those who reported oral contraceptive use (25.1 per 100 woman-years; adjusted hazard ratio 22.97 higher than other women; 95% CI: 5.0 to 105.4) or had 2 children. Birth outcomes were similar between trial arms, with 59.8% having full-term live births. No difference was detected in incident HIV during pregnancy compared with nonpregnant women (2.1 versus 4.3%; hazard ratio = 0.56, 95% CI: 0.14 to 2.26). Sexual activity was low in pregnancy and the early postpartum period, as was consistent condom use. Conclusions:Pregnancy incidence was high despite trial participation being contingent on contraceptive use. We found no evidence that rates of HIV acquisition were elevated in pregnancy when compared with those in nonpregnant women. Risks from reductions in condom use may be offset by reduced sexual activity. Nevertheless, high HIV incidence in both pregnant and nonpregnant women supports consideration of introducing antiretroviral-containing preexposure prophylaxis for pregnant and nonpregnant women in high HIV prevalence settings.

show abstract

Section: Discussionmentioning

confidence: 99%

“…45,46 Trials that include pregnant women can generate these insights prelicensure. To complement these approaches, well-designed, postlicensure pregnancy registries that can 47 This study had a number of strengths and limitations. The study had a high retention rate, monthly contraceptive counseling, and pregnancy assessments.…”

Section: Discussionmentioning

confidence: 99%

HIV Incidence Among Pregnant and Nonpregnant Women in the FACTS-001 Trial: Implications for HIV Prevention, Especially PrEP Use

Rees

Chersich

Munthali

et al. 2021

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

show abstract

“…Fetal exposure is evidently unavoidable during clinical trials that include women of childbearing potential. 26,27 Structures are needed to collect postmarketing safety and efficacy data of sufficient quality and quantity to assess outcomes from exposures in pregnancy.…”

Section: Discussion Products For Pregnant and Breastfeeding Womenmentioning

confidence: 99%

Long-acting or extended-release antiretroviral products for HIV treatment and prevention in infants, children, adolescents, and pregnant and breastfeeding women: knowledge gaps and research priorities

et al. 2019

View full text Add to dashboard Cite

Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10-19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations. Research should focus not only on how best to transition long-acting products to these populations, but also on early engagement across sectors and among stakeholders. A parallel rather than sequential approach is needed when establishing adult, adolescent, and paediatric clinical trials and seeking regulatory approval. Pregnant and lactating women should be included in adult clinical trials. Adolescent-friendly trial design is needed to improve recruitment and retention of young people.

show abstract

“…Some studies have allowed women who become pregnant to continue on the study drug, and conducted additional PK evaluations on these women. However, the number of evaluable women tends to be fairly small [96]. Overall, opportunistic evaluations can provide the basis for dosage recommendations in pregnancy, raise concerns requiring further prospective study and provide some description of drug safety.…”

Section: Antiretroviral Pharmacokinetics During Pregnancy: Implicatmentioning

confidence: 99%

Inclusion of pregnant women in antiretroviral drug research: what is needed to move forwards?

et al. 2019

Self Cite

View full text Add to dashboard Cite

Introduction To adequately ascertain drug safety and efficacy, drug trials need to include participants from all groups likely to receive the medication following approval. Pregnant women, however, are mostly excluded from trials, and women participating are often required to use highly effective contraception and taken off study product (even off study) if they conceive. There is little commercial incentive for including pregnant women in clinical trials, even when preclinical animal and human pharmacokinetic and safety data appear reassuring. With this conservative approach, large numbers of pregnant women are exposed to drug postlicensing with little known about drug safety and efficacy, and little done to systematically monitor outcomes of pregnancy exposure. Discussion The article focuses on antiretrovirals for treating and preventing HIV, and presents potential approaches which could extend to other therapeutic areas, to obtaining adequate and timely data to inform use of these drugs in this population. Most importantly the pregnancy risk profile of investigational agents can be systematically stratified from low to high risk, based on guidelines from regulatory bodies. This stratification can determine the progress through preclinical work with animals and non‐pregnant women to opportunistic studies among women who become pregnant on a clinical trial or within routine clinical treatment. Stratification can include pregnant women in clinical trials, concurrent with Phase II/III trials in non‐pregnant adults, and ultimately to postmarketing surveillance for outcomes in pregnant women and their infants. Each step can be enabled by clear criteria from international and local regulatory bodies on progression through study phases, standardized protocols for collecting relevant data, collaborative data sharing, pregnancy outcomes surveillance systems supported by committed funding for these endeavours. Conclusions A formalized step‐wise approach to including pregnant women in antiretroviral drug research should become the new norm. Systematic implementation of this approach would yield more timely and higher quality pregnancy dosing, safety and efficacy data. Through more vigorous action, regulatory bodies could responsibly overcome reluctance to include pregnant women in drug trials. Funders, researchers and programme implementers need to be galvanized to progressively include pregnant women in research – the use of newer, more effective drugs in women is at stake (349).

show abstract

Getting pregnant in HIV clinical trials: women’s choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials

Cited by 4 publications

References 23 publications

HIV Incidence Among Pregnant and Nonpregnant Women in the FACTS-001 Trial: Implications for HIV Prevention, Especially PrEP Use

HIV Incidence Among Pregnant and Nonpregnant Women in the FACTS-001 Trial: Implications for HIV Prevention, Especially PrEP Use

Long-acting or extended-release antiretroviral products for HIV treatment and prevention in infants, children, adolescents, and pregnant and breastfeeding women: knowledge gaps and research priorities

Inclusion of pregnant women in antiretroviral drug research: what is needed to move forwards?

Contact Info

Product

Resources

About