Women under-represented in HIV clinical trials

Less than a quarter of people taking part in clinical trials for antiretroviral medications are women, potentially limiting the generalisability of findings, according to a systematic review published in the February 1 edition of the Journal of Acquired Immune Deficiency Syndromes.

The authors say that gender differences in prevalence, incidence, symptoms, disease progression and outcomes have been noted across a range of diseases. Differences in pharmacokinetics (how drugs are absorbed and distributed in the body) and pharmacodynamics (the effect of a drug on the body) can result in differences in side-effects and response to treatment.

Moreover gender differences in power, personal relationships, life experiences and health literacy can influence people’s risk of infection, health-seeking behaviour and use of health services.

Glossary

retention in care

A patient’s regular and ongoing engagement with medical care at a health care facility. 

disease progression

The worsening of a disease.

clinical trial

A research study involving participants, usually to find out how well a new drug or treatment works in people and how safe it is.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

cure

To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 

Limited participation of women is a concern for clinical trials across a wide range of disease areas, but the problem appears to be particularly acute in HIV.

The researchers searched for clinical trials of antiretroviral medications (of any phase) that were published in eight major medical journals. In order to examine evolution over time, three time periods were selected: 1994-1997, 2001-2004 and 2008-2011.

In 387 separate studies with 95,305 participants, only 23% of participants were female. The average proportion in each individual study was 19%. The average has improved over time – from 9% in the mid-1990s to 22% more recently.

Research conducted in higher-income countries involved fewer women.

Studies funded by universities and charitable foundations recruited more women than pharmaceutical companies and public bodies. Although the US National Institutes of Health has been legally obliged since 1993 to only fund studies which will allow meaningful gender comparisons, in the third of the studies which they part-funded only 20% of participants were women.

The researchers also examined 53 clinical trials of vaccines for HIV prevention. An average of 38% of participants were women. However in 104 studies working towards a cure for HIV, the average rate of female participation was only 11%, with over a quarter of studies recruiting no women at all despite both sexes being eligible.

“Our study showed a persistent under-representation of women in HIV clinical trials,” comment the authors. “Only with sufficient knowledge of sex and gender differences and similarities can optimal and evidence-based treatment, prevention, and care be delivered to both women and men living with or at risk for HIV.”

They note barriers limiting women’s participation in studies – safety concerns especially in relation to unborn children, requirements to use contraceptives while taking part, family and caregiving responsibilities making time commitments challenging, socio-economic inequalities, low education and lack of understanding of what trials are.

The authors also point to a phase III clinical trial in the United States which sets out to address these barriers and in which 67% of participants were women (mostly women of colour). Clinics with large numbers of female patients (primarily in the Deep South) were selected as study sites even if they had less experience of running clinical trials; study sites had quotas requiring more female than male participants; an experienced patient advocate worked with clinics on tailored recruitment strategies; outreach activities were conducted; community groups were engaged with; the reimbursement of transport and childcare costs was publicised; and enrolment criteria were broad.

Nonetheless those running this trial reflected that they should have given as much attention to retention strategies as to initial recruitment – individualised support to help women continue to engage with healthcare might have improved retention in this study.