An injectable drug that protects people at high risk of HIV infection has been recommended for use by the World Health Organization (WHO). Cabotegravir (also known as CAB-LA), which is given every two months, was initially approved by the US Food and Drug Administration in December 2021.
Cabotegravir is currently manufactured by ViiV Healthcare, a UK-based company jointly owned by GSK in London, Pfizer in New York City and Shionogi in Osaka, Japan. On 28 July, the day that the WHO issued its recommendation, ViiV announced a voluntary licensing agreement in which up to three other companies would be allowed to produce and supply generic versions of the drug; these would be intended for use in 90 of the world’s lowest-income countries, where the majority of new HIV cases occur.
“We believe that widening access to cabotegravir could be game-changing in HIV prevention and could significantly contribute towards the goal of ending the HIV epidemic,” a ViiV Healthcare spokesperson said. But many are concerned that the drug will be too expensive to have an impact. Campaign groups say that the drug’s price tag — estimated at US$3,700 per vial in the United States — puts it out of reach of the poorest countries. The medical charity Médecins sans Frontières, also known as Doctors Without Borders, has called the licence “limited and disappointing”.
ViiV has promised to provide the drug at a “not for profit price” for public programmes in low-income countries. It has not said what this price would be — but it has told Nature that it will be more than $10 per dose, the price that campaign groups are urging.
Some 1.5 million people (between 1.1 million and 2 million) became infected with HIV in 2021, according to the latest update from the Joint United Nations Programme on HIV/AIDS (UNAIDS), also published last week. The majority of new infections and deaths occur in Africa. Between 510,000 and 860,000 people died from HIV in 2021, according to the UNAIDS update.
Cabotegravir is the latest WHO-recommended drug that protects against HIV infection. In January 2021, the agency approved the use of a vaginal ring coated with the anti-HIV drug dapivirine. And in 2015, the WHO recommended an oral pill, tenofovir disoproxil (TDF), which is also available in generic forms and is in use in some 80 countries.
Uninfected people can use the pill discretely and not at the time of sex — characteristics that could make such medication especially important for young women and adolescent girls, UNAIDS says. Studies, however, have shown that women and girls can be reluctant to take it because of the stigma associated with the disease, and also from the fear of violence if they are found out.
A study1 published in April showed cabotegravir to be more effective than TDF in preventing HIV. Moreover, it does not need to be taken so often, and the vaccine can be administered in a clinic, potentially providing more privacy.
The study, led by Sinead Delany-Moretlwe, director of research at the Wits Reproductive Health and HIV Institute in Johannesburg, reported the results of a phase III clinical trial in South Africa between 2017 and 2020. It involved 3,224 women, with half given the injection and half taking oral tablets. Forty HIV infections were reported during the trial period: 4 in the cabotegravir group and 36 in the oral-pill group. “Access to cabotegravir as an additional choice should be a priority,” Delany-Moretlwe told delegates at the 24th International AIDS Conference in Montreal, Canada, last week.
Who will pay?
The WHO’s cabotegravir announcement — and ViiV’s licensing deal — garnered both praise and criticism from many attending or following the conference, which ended on 2 August. “Affordability is the most significant barrier to global implementation,” said Iskandar Azwa, an infectious-disease specialist at the University of Malaya in Kuala Lumpur, at the conference.
According to a preprint2 from Lise Jamieson, a biostatistician at the University of the Witwatersrand in Johannesburg, and her colleagues, posted in March this year, each injection would need to be priced at between $9 and $14 to be similar to or more cost-effective than an oral pill. An analysis from the Clinton Health Access Initiative, a philanthropic health-care organization based in Boston, Massachusetts, presented at a workshop in February suggested that generics manufacturers could produce cabotegravir for around $20 per person per year.
For now, additional international funding for HIV/AIDS drugs will be a tough request, the conference heard. Indeed, official assistance from many large bilateral donors outside the United States has plummeted by 57% over the past decade. Overall, in 2021, international resources available for HIV were 6% lower than in 2010, according to UNAIDS. On this basis, an expensive new drug will not be affordable, researchers and campaigners are arguing.
In an open letter to ViiV’s chief executive Deborah Waterhouse, a group of more than 70 politicians, civil-society activists, researchers and heads of philanthropic organizations urged the company to set the price of cabotegravir “as close as possible” to that of existing HIV prevention medicines, which they say is around $60 per person per year — equivalent to $10 per cabotegravir dose.
A ViiV spokesperson said in an e-mail to Nature that a $10 price is not realistic because cabotegravir is more complex and therefore more expensive than “a simple white tablet”. Moreover, a low price could prevent generics manufacturers from coming forward. “It’s important not to stifle generic interest in development and manufacture through the voluntary licence agreement we have just finalized by setting unrealistic expectations on price now.”
The spokesperson said all manufacturers are welcome to apply to make generic copies of the drug, and that three licences will be awarded in the first instance. “We have the ability to increase the number of sub-licensees in future if we think the demand signals are supportive and there is a need,” the spokesperson added.