By Esther Nakkazi
Uganda will participate in a clinical trial that will evaluate the safety and efficacy of a six months long-lasting injectable, Lenacapavir (LEN), and an oral daily pill, Descovy (F/TAF) as pre-exposure prophylaxis (PrEP) products.
These products will be compared to Truvada (TDF) that is already in use as PrEP in many African countries including Uganda for preventing HIV infection.
The Gilead Women’s PrEP Study will enroll about 5,000 participants – only adolescent girls and young women (AGYW) at high risk of HIV infection and will happen in both Uganda and South Africa.
In Uganda, the study will be led by Dr. Flavia Matovu Kiweewa of the Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration and will be conducted at the sites in Kalangala, Masaka, Mubende, Mityana, Lwamata, Hoima, and Kapeeka. Other study sites are located in South Africa.
The primary objective of the study is to evaluate the efficacy of Lenacapavir for HIV PrEP and to evaluate the efficacy of F/TAF for HIV PrEP in adolescent girls and young women, said Alex Kintu, a member of the Gilead research team.
“We would like that the studies are conducted in regions with a high background HIV incidence so that we know that the drugs we will be assessing can work for HIV prevention,” said Kintu.
Study design and benefits:
The study will be a double-blinded randomized, phase three trial in which every participant gets an injection and a pill. Participants will be randomized into one of the three groups and they will not know what group they are in. If they are in the Lenacapavir group, they will receive an active shot of long-acting subcutaneous Lenacapavir and a placebo pill. If they are in the Truvada or Descovy group, they will receive an active pill of Truvada or Descovy and a placebo shot.
One arm of participants will be given Descovy – a smaller pill than Truvada used for PrEP. Following findings from the DISCOVER trial that were released in 2019, the US Food and Drug Administration has approved Descovy as a second option for PrEP in men who have sex with men and transgender women but not cisgender women.
This is why we are conducting this study in women specifically women in Africa with the highest burden of HIV, said Moupali Das, Executive Director of PrEP clinical development at Gilead Sciences.
The study will be only for adolescent girls and young women (AGYW) aged 16-30 years and at high risk of HIV infection. The rationale for the inclusion of these is because girls in this age group have a high HIV incidence and “prevention of HIV of infection in adolescent girls may have a significant impact on life course and trajectory,” said Kintu.
Different from other studies, study participants who become pregnant and those who are breastfeeding in this study will be allowed to continue after providing informed consent to continue on study product.
“We will be evaluating two new options of prevention at the same time – the long-acting injectable Lenacapavir and a smaller pill Descovy for PrEP, compared to Truvada for PrEP,” said Das.
“I look at this as an opportunity for us to cut down on the levels of HIV transmission. One of the ways why people are not suppressing the virus is because they are not adhering but this will be addressed by this single injection,” said Ruth Owori, an HIV positive AGYW.
In a closed virtual meeting held on 12th November 2020 with key stakeholders including Ministry of Health, National Drug Authority (NDA), Uganda National Council for Science and Technology (UNCST), Institutional Review Boards (IRBs), scientists, PrEP implementing Partners, and Civil society participants agreed that the long-acting injection given twice a year as PrEP will be convenient and tally well with the long-acting family planning method Depo Provera as well users do not have to worry about food before using it.
About 15 million women in sub-Saharan Africa use Depo-Provera, it is popular because it is a reversible contraceptive, it is safe, discreet, highly effective when used consistently (less than 0.2% failure rate), and easy to administer (IM injection) by the health workers. Women have to pick up Depo Provera every three months.
“The long-acting PrEP is important for women at risk. Truvada is effective but we do not know if women really take it at least for us in resource-limited settings. The idea of trying to take a pill a day is hard so I think that the long-acting PrEP is so important for women obviously the longer the better,” said Philippa Musoke an associate professor at the Department of Child Health at Makerere University and principal researcher at MU-JHU.
Having an injection every six months for women at risk who may also be taking Depo-Provera every three months means that these women participate less in trying to engage in PrEP and only have to come a few times to the health facilities, said Dr. Kiweewa
The current oral PrEP pill has had challenges including low uptake due to stigma, poor access due to long distances that make it difficult for women to continuously go to the health facilities, and forgetting to swallow the daily pill. In addition, the fact that the pill resembles ARVS and is dispensed in similar tins that make noise further limits PrEP uptake.
“I feel that women embrace PrEP but the issues are around poor access and uptake. Using a long-acting injection for six months will solve some of the barriers of adherence to PrEP, said Dr. Herbert Kadama, Chair MOH, PrEP Technical Working Group.
“Whereas we have a wide range of interventions that we are implementing to address HIV, we continue to experience significant deaths. We think that we need to expand PrEP which we are implementing but not yet up to scale, said Joshua Musinguzi, the head of the AIDS control program at the Ministry of Health.
“This is a game-changer of sorts on how we can approach PrEP…..the longer-acting technologies will move us a long way and help us in programming and impacts of our intervention,” said Dr. Musinguzi.
A young lady now who is HIV negative and with an HIV positive husband and almost three and a half years since she was initiated on PrEP said it has made her relationship more interesting and stronger.
“PrEP has enabled me and my husband to have an HIV-negative baby who is now three years old which would not be possible if we were using condoms. PrEP has made our sex life more interesting since we have no worries about getting infected. I am 100 percent sure that I will stay HIV negative if I adhere to PrEP,” she said.
Stakeholders on the zoom meeting were concerned about having pregnant and breastfeeding women in the study when there is limited data about LEN in pregnancy and in breast milk, how to involve men in the study because ‘behind every pregnant woman there is a man’ and on how to consent, adolescent girls, especially those below 18 years and have to get ascent from their parents.
“How do you maintain confidentiality and enroll girls who are sexually active,” wondered Dr. Sabrina Bakeera-Kitaka a pediatrician and a senior lecturer at Makerere University College of Health Sciences. “By requesting parents to give consent for a girl who is sexually active you are breaking confidentiality.”
The researchers said that the girls’ confidentiality will be protected as well as women who fall pregnant and are breastfeeding will have to be re-consented to establish if they are still willing to participate in the study.
“ There is a need for more treatment and therapeutic options that can safely be used in pregnancy. More clinical trials are therefore now adopting strategies for safely following up pregnant women on investigational study drugs,” assured Kintu.
“We will have an extensive clinical safety database on Lenacapavir before trial initiation, and will closely monitor pregnant and breastfeeding women throughout the study,” said Das.