Two studies presented at the IAS 2021 conference underline the therapeutic value of the new injectable antiretroviral lenacapavir, both for people in escape, and as part of a first-line treatment.
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Lenacapavir, developed by Gilead, is an HIV capsid inhibitor with a very long half-life once injected into the body: It only takes two subcutaneous injections per year for it to be effective.
CAPELLA study: lenacapavir for escapees
CAPELLA is a study seeking to estimate the effectiveness of Lenacapavir in people on treatment withdrawal. At the start of the study, participants had to be on treatment, have a viral load greater than 400 copies, have resistance to at least two molecules among all classes of commonly used antiretroviral (ARV) drugs, and be able to rely only on the full effectiveness of two molecules in total. In CAPELLA, the effects of lenacapavir are not evaluated against a placebo and all participants will receive the injections, but at different times and with different combinations of ARVs in parallel. A total of 72 people were recruited in this study.
The first results, presented earlier this year at CROI 2021, already showed that, within the first two weeks, 88% of participants had noticed a drop of at least 0.5 logs in their viral load. Six months later, Professor Jean-Michel Molina (Saint-Louis hospital, Paris) presented new results measured just after the second annual injection. The data relate to 36 of the 72 participants, those who were actually receiving the equivalent of Lenacapavir monotherapy, since the ARV combination used in parallel is unfortunately ineffective. In this group, by week 26, 81% of participants have a viral load below 50 copies / ml and 89% have a viral load below 400 copies / ml. These results confirm the interest of this new injectable for people in exhaustion. No serious side effects were seen, but 18% of participants developed nodules or lumps under the skin at the injection site for 22 weeks, and 11% saw thickening of the skin at the injection site. for about 10 weeks.
CALIBRATE study: Lenacapavir for starting treatment
The first results of the CALIBRATE study suggest for its part that lenacapavir would also be effective as part of a first-line treatment, in combination with at least one other molecule. Data at 28 weeks, i.e. after the first injection, were presented by Professor Samir Gupta (Indiana University, USA). CALIBRATE is a study of 182 people living with HIV, with an average age of 29 years, without ARV treatment at the start of the study and with a CD4 count greater than 200. Fifteen percent of participants had a viral load quite high, starting at over 100,000 copies / mm3.
The study combines lenacapavir with tenofovir-alafenamide (TAF) and emtricitabine (FTC), then to TAF and bictegravir only, and compares it to an oral combination of bictegravir and TAF / FTC. In the arm evaluating the injectable version of lenacapavir, participants began with daily treatment with tablets, followed by injections every six months. The first data show excellent efficacy, with 94% virological success and only one person showing partial resistance, including one to HIV capsid inhibitors.
Regarding side effects, if the injection was well tolerated, 11% of participants reported injection site nodules and 17% reported pain, redness and swelling.
These encouraging results prompt the authors to request further trials, with lenacapavir in combination this time with islatravir, another prolonged-release injectable treatment.
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