High levels of adherence to study medication among women who conceived during HIV PrEP study

HIV pre-exposure prophylaxis (PrEP) appears to be an acceptable strategy for safer conception for HIV-negative women in a relationship with an HIV-positive partner, according to the results of a study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Data from the Partners PrEP study showed there was a high incidence of pregnancy and that adherence to study medication was equally high among women who became pregnant and those who did not conceive.

“By multiple measures,” write the authors, “adherence to study drug (blinded PrEP or placebo) was high among women experiencing pregnancy.”

PrEP is a very promising biomedical method of HIV prevention. It involves an HIV-negative individual taking daily antiretroviral therapy to reduce their risk of infection with HIV.

Glossary

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

plasma

The fluid portion of the blood.

blinding

When a clinical trial is blinded, the participants are unaware as to whether they are receiving the experimental drug or a placebo (or another drug). Double blinding refers to the participant, their doctor and researchers running the trial not knowing which treatment is received by each group until all data have been recorded. Blinding is done to reduce bias in clinical trials.

demonstration project

A project that tests and measures the effect of a treatment or prevention approach in a ‘real world’ setting. Usually done after clinical trials have shown that the intervention is efficacious, but while there are outstanding questions about how it can be best implemented.

The efficacy of PrEP depends on adherence. Investigators from the Partners PrEP study wanted to see if women who conceived during the trial were adherent to their therapy.

Serodiscordant heterosexual couples in Kenya and Uganda were recruited to the research. None of the HIV-positive partners were taking antiretroviral therapy. The authors focused on 1785 couples where the female partner was HIV negative. They gathered data on pregnancy incidence and compared rates of adherence to allocated medication (PrEP or placebo) between women who conceived and those who did not. Adherence was assessed by pill count. Participants who took 80% or more of their doses were classified as highly adherent. A sub-set of patients taking tenofovir/emtricitabine PrEP had their plasma concentrations of the drug monitored.

The women had a median age of 33 years. Approximately a quarter (23%) reported unprotected sex in the month prior to enrolment in the study and 53% were not using effective contraception.

During 2828 person-years of follow-up, 267 women had 288 pregnancies, an incidence of 10.2 per 100 person-years.

Factors associated with conceiving included reporting unprotected sex, having an additional sexual partner, younger age and not using effective contraception.

Adherence to study medication was high. Pill count revealed that 97% of dispensed doses were taken by women who conceived, compared to 98% of doses for women who did not become pregnant. Some 98% of women who fell pregnant were classified as highly adherent as were 99% of women who did not conceive.

There was no evidence that planning to conceive had an impact on pill taking. For the women who became pregnant, adherence rates in the three months before conception were no different to their adherence rates at other times during the study or to the levels of adherence observed in women who did not conceive.

To further assess adherence, the investigators evaluated plasma concentrations of tenofovir in 73 women who became pregnant and 103 women who did not conceive.

The drug was detected in 71% of samples obtained from women who conceived compared to 81% of samples from women not conceiving. This difference was not significant.

“These data suggest that women were willing to use PrEP around the time of conception,” comment the investigators. “Now that emtricitabine/tenofovir is approved and recommended for use as oral PrEP, and there is enthusiasm for PrEP as a safer conception strategy, implementation and demonstration projects should include women with pregnancy and/or plans for pregnancy in order to understand the risks, the benefits, and challenges to biomedical prevention in this high priority group.”

References

Matthews LT et al. High medication adherence during periconception periods among HIV-1-uninfected women participating in a clinical trial of antiretroviral pre-exposure prophylaxis. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI. 0000000000000246 (2014).