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Long-acting cabotegravir - focus on transgender women

The overall results from trial HPTN 083 were previously reported in this issue of TreatmentUpdate. In this trial, researchers compared the protective effects of daily oral tenofovir DF + FTC (sold as Truvada and available in generic formulations; hereafter abbreviated to TDF + FTC) vs. long-acting injectable cabotegravir (LA cab). Analysis found that LA cab was safe and highly effective in reducing the risk of HIV infection.

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The trial enrolled 570 transgender women—304 were assigned to received TDF + FTC and 266 were assigned to receive injectable cabotegravir.

At the time they entered the study, participants were on average around 23 years old. Almost half of the participants reported emotional intimate partner violence, while almost one-third reported physical intimate partner violence. Nearly 30% of all transgender women reported that they were not at risk for HIV infection. Nearly 25% of transgender participants reported what researchers termed “clinically significant” symptoms of depression.

Results

There was a total of nine newly diagnosed HIV infections during the study, distributed as follows:

  • TDF + FTC – seven infections
  • LA cab – two infections

Researchers found that participants assigned to take TDF + FTC who developed HIV had no or very low blood levels of TDF. In other words, they did not take sufficient medication. Indeed, in five of the seven participants who tested positive for HIV, no concentration of TDF could be detected in their blood samples.

One participant had HIV infection detected at the fourth week of the study, while they were supposed to be taking the oral formulation of cabotegravir prior to switching to the injectable formulation. Adherence was not directly observed, so researchers are not certain if the participant used oral cabotegravir consistently. Researchers stated that “it is possible that the participant acquired HIV shortly after enrollment and that this was not detected until the week four visit [to the study clinic].”

The other participants acquired HIV several years after their last injection of cabotegravir. Analysis of their blood samples around the time of infection did not detect any cabotegravir.

Hormones

Upon study entry, 44% of transgender women reported that they were using gender-affirming hormones. Subsequently, a further 14% of participants reported use of these hormones.

Commonly used hormones for gender affirmation by participants in this study included the following:

  • estradiol valerate
  • spironolactone
  • estradiol
  • cyproterone acetate

There were no differences in types of gender-affirming hormones used among participants who received TDF + FTC and those who received LA cab.

Use of gender-affirming hormones did not result in significant increased weight in transgender participants during the study.

Based on data from a sub-study of 53 transgender women, use of gender-affirming hormones did not affect cabotegravir levels in the blood.

Adverse events

Adverse events is the term used to describe unfortunate events that occur in a clinical trial. Adverse events can be caused by the study drug(s), an underlying illness or infection, or other issues unrelated to the study.

Adverse events were similar in participants regardless of whether they received TDF + FTC or LA cab. They were also similar in transgender women and cisgender men (data on these men came from the overall study analysis previously reported).

Two transgender people died during the study; their deaths were not related to the study medicines. Details were not released by the research team.

For the future

Based on the analysis of data from transgender women, the researchers stated that “an injection [of long-acting cabotegravir] every 2 months is convenient and discreet and might address the barriers to daily oral pill-taking, such as competing life priorities, HIV stigma, discrimination and violence” faced by transgender women.

The researchers used a relatively small number of transgender women to collect data about the potential for gender-affirming hormones to interact with cabotegravir (and vice versa). They called for additional studies to better understand this issue.

—Sean R. Hosein

REFERENCE:

Marzinke MA, Hanscom B, Wang Z, et al. Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial. Lancet HIV. 2023 Nov;10(11):e703-e712.