- Doctors studied a new HIV prevention drug that is injected every two months
- 3,223 women entered the clinical trial of injectable cabotegravir
- Long-acting cabotegravir reduced the risk of HIV infection and was generally safe
Taking anti-HIV drugs prior to possible sexual exposure in order to reduce the risk of acquiring HIV infection is called pre-exposure prophylaxis (PrEP). Truvada, a pill containing two anti-HIV drugs (tenofovir DF + FTC), is approved as PrEP in Canada and many other countries. It is also available in generic formulations. A majority of clinical trials have tested Truvada as PrEP when taken as one pill every day.
Some people dislike taking pills and/or may not remember to take them. Pharmaceutical companies are developing drugs for PrEP that need infrequent dosing. Some clinical trials have found that taking Truvada less frequently—on an “on demand” schedule—can also significantly reduce the risk of HIV infection.
The pharmaceutical company ViiV Healthcare is developing a form of PrEP with a long-acting formulation of the drug cabotegravir (cabotegravir LA). The drug is injected deep into muscle every two months and is slowly released from muscle into the blood.
Study HPTN 084
The U.S. National Institutes of Allergy and Infectious Diseases (NIAID), ViiV Healthcare and the Bill and Melinda Gates Foundation sponsored a study called HPTN 084. This study recruited 3,223 HIV-negative cisgender women who were at increased risk for HIV infection. The study took place in seven countries in Southern Africa and was randomized, double-blind and placebo controlled.
For the first four weeks of the study, participants took one of the following combinations orally:
- a cabotegravir tablet + a placebo Truvada tablet
- a Truvada tablet + a placebo cabotegravir tablet
This lead-in period was to ensure that participants did not develop side effects from cabotegravir. At the end of this time, participants were randomly assigned to receive one of the following interventions:
- long-acting cabotegravir injection + a placebo Truvada tablet
- placebo injection + a Truvada tablet
Participants were expected to be in the study for up to three years.
An early end to the study
An independent committee overseeing the study recommended that HPTN 084 be prematurely unblinded because the regimen of cabotegravir LA was better at protecting women than daily oral Truvada. The distribution of HIV infections was as follows:
- cabotegravir LA injection – 4 women; 0.21% incidence of HIV
- daily oral Truvada – 34 women; 1.79% incidence of HIV
According to the research team, cabotegravir LA was statistically “superior” to daily Truvada in its ability to protect women. Nine-fold more women taking daily Truvada became HIV positive vs. women taking cabotegravir LA. Another way to interpret the study results is that cabotegravir LA was almost 90% more effective than daily Truvada.
Thousands of people have received cabotegravir in clinical trials. In general, this drug is generally well tolerated. In trial 084, about 32% of women reported temporary pain at the injection site whether they got cabotegravir or placebo.
Research is underway to find out why some women taking cabotegravir LA became HIV positive. This research will also assess if the women have a strain of HIV that developed the ability to resist cabotegravir.
A similar study
The results from HPTN 084 with women are exciting and complement an earlier study of cabotegravir LA in 4,570 gay/bisexual men and transgender women—HPTN 083. In that trial, cabotegravir LA was also found to be highly effective at reducing the risk of HIV infection by about 66%.
Bold steps are needed to broaden access
It is likely that ViiV Healthcare will seek regulatory approval for cabotegravir LA to reduce the risk of HIV infection by the first quarter of 2021. After licensure, a critical aspect for ensuring that cabotegravir LA is widely used will be setting its price. In the coming year, ViiV has the opportunity to take a bold step: to set a modest price for this highly effective HIV prevention drug. A high price will likely mean that only people with private insurance coverage will get access to cabotegravir LA. ViiV will have spent much money and many years developing a drug that relatively few people can use if its price is high. By setting an affordable price for cabotegravir LA, ViiV can recoup its research and development cost over time and make a profit, as more people will be able to access the drug.
Nearly a decade ago, clinical trials found that Truvada was highly effective at reducing the risk for HIV. However, it took public drug subsidy programs (commonly called formularies) years before they finally agreed to pay for Truvada, and many waited until cheaper generic versions were available. It would be unfortunate if a similar situation happened with cabotegravir LA or other highly effective drugs for PrEP that are under development.
The coronavirus pandemic has devastated important sectors of the economy. This has reduced tax revenue for governments, which have had to borrow huge sums to support the economy. A result is that the cost of new drugs is likely to become a more pressing issue across many health conditions in the future. This looming future should stimulate all pharmaceutical companies to elaborate on new ideas about financing drug development. In this way, formularies remain sustainable and companies can keep the gates open for new medicines to come to market.
—Sean R. Hosein
Long-acting injectable drug prevents HIV – CATIE News
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