Two-monthly cabotegravir injections prevent HIV infection in African women: HPTN 084 study recommends early unblinding

On 9 November 2020, ViiV Healthcare announced new results showing that cabotegravir injections are highly effective as pre-exposure prophylaxis (PrEP) to prevent HIV infection in African women. [1]

This was based on a planned early analysis of the large randomised placebo-controlled international HPTN 084 study being run at 20 sites in seven countries in sub-Saharan Africa (Botswana, Kenya, Malawi, South Africa, Eswatini, Uganda and Zimbabwe). [2]

The results match a similar study last year in gay men and transgender women (HPTN 083). [3, 4]

Taken together cabotegravir injections could be submitted for approval as PrEP irrespective of sex and gender.

HPTN 084 randomised 3223 women at high risk of HIV to either cabotegravir injections every two months or to currently approved TDF/FTC taken as a daily oral pill, plus matched placebos. A planned interim analysis by the Data and Safety Monitoring Board (DSMB) found that cabotegravir was sufficiently better than oral PrEP that the comparative part of the study should finish early. This will mean that all participants will be offered cabotegravir injections.

So far, 38 women have become HIV positive. Of these, 4 were in the cabotegravir group and 34 were randomised to daily TDF/FTC. The HIV incidence rates for each group were 0.21% (95% CI: 0.06% to 0.54%) and 1.79% (95% CI 1.24% to 2.51%), respectively. This also made cabotegravir significantly more effective than TDF/FTC – by 89% (95% CI 68-96%).

However, the report also emphasised that both versions of PrEP were highly effective, which is important. With good adherence, oral PrEP is already known to be more than 99.9% effective, with low adherence usually explaining any infections. This is key to understanding the importance of the new results: many people find taking pills difficult so the option to only need six injections a year can provide a wider choice of PrEP, including to people who are not interested in taking oral pills.

Limited other details were included in the press statement, but serious side effects were rare in each group. Significantly more participants receiving active injections reported skin reactions at the injection site than with placebo injections (32% vs 9%), but these were generally mild and no women left the study for this reason.

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The early results are good news and will hopefully allow for earlier application to regulatory agencies for approval.

The option to use either injections or pills will broaden the options for people who want to use PrEP. Many people find taking a daily pill difficult and missing doses of oral PrEP is the likely explanation for injections being more effective in both 083 and 084 studies.

HPTN 083 also reported cabotegravir injections were significantly more effective at preventing infections, with a similar explanation that the difference would be from people being less adherent with oral pills.

References

1. ViiV Healthcare press statement. ViiV Healthcare announces investigational injectable cabotegravir is superior to oral standard of care for HIV prevention in women. (9 November 2020).
   https://viivhealthcare.com/en-gb/media/press-releases/2020/november/viiv-Healthcare-announces-investigational-injectable-cabotegravir-is-superior-to-oral-standard-of-care-for-HIV-prevention-in-women
2. ClinicalTrials.gov. Evaluating the safety and efficacy of long-acting injectable cabotegravir compared to daily oral TDF/FTC for pre-exposure prophylaxis in HIV-uninfected women.
   https://clinicaltrials.gov/ct2/show/NCT03164564a
3. Cabotegravir long-acting injections prevent HIV as PrEP, HTB (1 June 2019).
   https://i-base.info/htb/37961
4. Long-acting cabotegravir injections are effective as HIV PrEP in gay men and transgender women: results from HPTN 083. HTB (22 July 2020).
   https://i-base.info/htb/38534

 This article was first posted on 9 November 2020.