Day 4; July 26th 2024
by Joe Caperna
Many important reports today. Most of today’s summary will focus on Artistry-1.
ARTRISTRY-1
Efficacy and Safety of Bictegravir Plus Lenacapavir: 48-Week Outcomes in Virologically Suppressed People With HIV-1 on Complex Antiretroviral Regimens at Baseline.” This was a switch study, meaning on an effective regimen, fully suppressed, and ‘switched’ to another treatment. Patients were on up to five drugs at a time, then switched to just two drugs, a simplified regimen of once daily oral bictegravir plus lenacapavir. (Lenacapavir was just announced in every 6-month injectable form to prevent 100% of HIV infections in African women. This study used daily oral.
This study was randomized for drug doses, making the results stronger. The regimen was effective and tolerated. It is important to know that this is not a recommended regimen, only being studied. The study compared different doses and found the most effective dose of each medicine. This combination cannot be used with active Hepatitis B.
Sorana Segal-Maurer, MD, principal investigator on the ARTRISTRY-1 trial, commented that
In general, we don’t really focus on people with HIV who are virologically suppressed, because they’re suppressed. We don’t always think that it’s burdensome to take multiple pills a day. And these persons are getting older, they’re having more metabolic comorbid conditions, more drug interactions,” she stated.
“This is the population of persons with HIV that was singled out as sort of being left behind—just because they’re suppressed. I think maybe we put them out of our mind. I like the focus of the study: Let’s make their lives simpler. Let’s make those drug interactions better, or less. It was a complex group—but they were all virally suppressed. So, it was a great opportunity to step in. I think it’s a tremendous study to offer persons with HIV,” Segal-Maurer said.
This was an ‘older’ group of 137 PLH on ARV’s, median age 60, most had a history of drug resistance (81%), a majority had been on ARV’s for 27 years and about 75% were on PI’s. With PI’s, there are food requirements, dangerous drug interactions and significant metabolic side-effects. About half were on twice a day regimen and a third were on 5 drugs, so this study made the regimen easier and safer. Females at birth were 19%, and Black race was 31%. This regimen was effective in almost everyone, with more than 90% of patients remain suppressed.
Bictegravir has a “high barrier to resistance.” Lenacapavir is a first-in-class capsid inhibitor, “where there’s no underlying resistance that persons with HIV would have if they’ve never taken it. So the 2 together can really offer a significant benefit or a potential for a good combination if somebody has prior history of resistance. They have very limited drug-drug interactions and no food requirement. This combination cannot be used with active Hepatitis B.
ARTISTRY-2 is planned in a larger group, with a new single tablet that has both drugs., bictegravir 75 mg plus lenacapavir 50 mg. It holds promise for an easier, safer and effective regimen in older PLH on arv’s for decades and with history of resistance. ARTISTRY-1 Reference
Do-Do Study (Dolutegravir and Doravirine)
This was another switch study, again in patients with resistance and this group was on arv’s for median of 27 years. There was median 3-year f/u, with up to 5 years on some, so longer f/u compared to the 48 weeks in ARTISTRY-1. The researchers checked drug levels, important to understand why a regimen ‘works’ or not. We learned that checking drug levels is common in Europe, where insurance or the health system pays for these tests. We do not have these tests easily available in the US. Study sites were in Germany and Austria. Patients were recruited from a prior study, comparing dolutegravir-FTC (Dovato©) with dolutegravir plus rilpivirine (NNRTI class with drug-interactions metabolic effects, and restriction to use acid blockers, PPI’s like omeprazole (Prilosec©), esomeprazole (Nexium©), lansoprazole (Prevacid©), pantoprazole (Protonix©).
Patients took dolutegravir with a newer NNRTI, doravirine (Pilfeltro©), which does not have the acid blocker restriction, metabolic effects and lower chance for drug interactions. 102/104 patients remained suppressed after median of 3 years. However, 13/104 (12%) stopped the regimen because of side-effects, 36/104 had no significant side-effects. This is another 2-drug combination that is not recommended yet but holds promise. This combination cannot be used in active Hepatitis B.
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New HIV preventive strategy sparks excitement— and protests—at AIDS conference
PrEP medications would need to cost less than $54 a year per patient for South Africa, for example, to afford them. Lenacapavir’s cost (injectable every 6 months) as HIV treatment in the United States in 2023 was $42,250 per new patient per year. Oral PrEP options, on the other hand, can cost less than $4 a month.
Generic cabotegravir (the current every 2 month injectable PrEP, called Apretude) will likely not be available in Africa until 2027. A group of MSF activists gathered at AIDS 2024 and called for an “immediate global action to break Gilead’s monopoly on lenacapavir.” NPR featured the protest on “Goats and Soda.”
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UNAIDS report shows AIDS pandemic can be ended by 2030,
but only if leaders boost resources and protect human rights now.
The report demonstrates that HIV prevention and treatment services will only reach people if human rights are upheld, if unfair laws against women and against marginalized communities are scrapped, and if discrimination and violence are tackled head on. There is great concern that funding for research, prevention and treatment will be cut, globally, and never eliminate HIV.
Lenacapavir is safe in pregnancy.
Importantly, this same injectable, lenacapavir, also known as Sunleca, HIV PrEP can safely be used during pregnancy.
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“Increased incidence of emergent integrase drug resistance with cabotegravir versus dolutegravir in randomized switching trials.” Abstract LB17
The researchers looked at patients reported in prior studies (ATLAS, FLARIR, LATTITUDE, CARES), who were using regimens with dolutegravir, one of the most common HIV medicines used worldwide. Although researchers reported low virologic failure with the dolutegravir regimens, they found that 65% of patients had INSTI mutations. The significance is not certain now, but worrisome that they reported such high level of mutations (65%) that could later affect the efficacy of INSTI’s.
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Sub-cutaneous rilpivirine/cabotegravir (Cabenuva©)
In a sub-study of the FLAIR phase 3 trial found that 93 patients were virologically suppressed on intramuscular Cabenuva and changed to under the skin injections. Although most (91/93) remained virologically suppressed, participants favored intramuscular injection of Cabenuva© over the subcutaneous version due to pain and the development of nodules and reddening of the skin.2. See review.