Researchers and activists in the trenches of the long fight against HIV got a rare piece of exciting news this week: Results from a large clinical trial in Africa showed that a twice-yearly injection of a new antiviral drug gave young women total protection from the virus.
“I got cold shivers,” said Dr. Linda-Gail Bekker, an investigator in the trial of the drug, lenacapavir, describing the startling sight of a line of zeros in the data column for new infections. “After all our years of sadness, particularly over vaccines, this truly is surreal.”
Yvette Raphael, the leader of a group called Advocacy for Prevention of HIV and AIDS in South Africa, said it was “the best news ever.”
The randomized controlled trial, called Purpose 1, was conducted in Uganda and South Africa. It tested whether the every-six-months injection of lenacapavir, made by Gilead Sciences, would provide better protection against HIV infection than two other drugs in wide use in high-income countries, both daily pills.
The results were so convincing that the trial was halted early at the recommendation of the independent data review committee, which said all participants should be offered the injection because it clearly provided superior protection against the virus.
None of the 2,134 women in the arm of the trial who received lenacapavir contracted HIV. By comparison, 16 of the 1,068 women (or 1.5%) who took Truvada, a daily pill that has been available for more than a decade, and 39 of 2,136 women (1.8%) who received a newer daily pill called Descovy were infected.
The findings were announced by Gilead. The data has not yet been subject to peer review. A second trial, conducted in six other countries, including Brazil and the United States, is assessing the effectiveness of lenacapavir in men who have sex with men, in transgender people and in those who use injection drugs. Midterm review of those results will take place later this year.
While Truvada, taken daily, provides high levels of protection against HIV infection and has been widely used by gay men in the United States and other high-income countries for years, it has not proved to be a potent prevention tool in Africa, where uptake has been low, particularly among young African women, the group with the highest rates of new infection.
The hope is that a twice-a-year injection, which women can put on their calendars and then not think about for months, will prove more effective.
“For a young woman who can’t get to an appointment at a clinic in a town, a young woman who can’t keep pills without facing stigma or violence, an injection just twice a year is the option that could keep her free of HIV,” said Lillian Mworeko, who leads a group called the International Community of Women Living With HIV Eastern Africa.
The outstanding question is access: Gilead charges $42,250 per patient per year for lenacapavir, in the United States, where it was approved as a treatment for HIV.
“Africa is excited. Women are excited. We have waited long for this,” Mworeko said. “Now we need to know, how do we get this into the hands of people who need it? We need an answer to this yesterday.”
Gilead said it was committed to making large volumes of the drug available “at prices that enable widespread availability” as quickly as possible at an accessible price in low-income countries with HIV incidence rates.
Janet Dorling, Gilead’s senior vice president for global patient solutions, said the company intended to sign voluntary licenses with generic drugmakers in several regions, sharing its intellectual property in exchange for a licensing fee so that eventually, a cheaper generic product would become available for low- and middle-income countries.
It can take generic makers years to get ready to produce a drug, and they need to have a sense of the potential market in order to commit to investing in production. So in the meantime, Gilead will aim to ship “sufficient volumes” of lenacapavir to low-income countries as soon as it has regulatory approval, she said.
Lenacapavir and the two pills studied are all known as preexposure prophylaxis drugs, or PrEP. Another effective injectable PrEP drug is available in some African countries, but its rollout has been bedeviled by access questions. Long-acting cabotegravir, which is delivered as an injection every two months, also showed excellent results in clinical trials in Africa. It is made by ViiV Healthcare, which is majority-owned by the pharmaceutical giant GSK; the company is charging $180 per patient per year for cabotegravir in developing countries, a price out of reach for most people and health systems in Africa.
South Africa’s current budget for oral PrEP is about $40 per patient per year.
Facing criticism by activists on pricing, ViiV granted a license to the Medicines Patent Pool, a United Nations-backed agency that tries to make medical technologies more accessible, which subsequently contracted with three generic makers. But none is expected to have a product available before 2027.
“Gilead has to have an access plan that is bold — not countries weighting up who will get it because they can’t afford to give it to everyone — or else this amazing clinical trial will not translate into any impact on HIV,” said Carmen Peréz Casas, who works on access to technologies to fight the virus at the global health initiative Unitaid.
The Purpose 1 trial is unusual for the young age of the participants, who were between 16 and 25, and for the fact that it enrolled pregnant and lactating women and kept women in the trial if they got pregnant. While pharmaceutical companies have historically been reluctant to test drugs in those groups, Mworeko said community participants were adamant that this trial must include those most at risk of new infection — that is, sexually active late-adolescent girls.
Lenacapavir is also the first HIV prevention drug for which trial results have become available for women before men; most are tested in gay men in industrialized countries before trials reach African women, long the most vulnerable population.
The New York Times News Service
