A multinational and multi -constitutional study led by Weill Cornell medicine researchers found little natural resistance to a new HIV therapy called Lenacapavir in a population of patients in Uganda.
The study, published on January 30 in the Antimicrobial Chemotherapy MagazineIt adds to the growing evidence that Lenacapavir can be a new powerful tool in the Global Arsenal of HIV medications. Approximately 1.5 million people live with HIV in Uganda.
“Our data show that only 1.6% of the individuals studied live with HIV strains that have resistance mutations associated with known Lenacapavir,” said Principal Author Dr. Ginebra Lee, assistant professor of Virology in Medicine at Weill Cornell Medicine. “That is important because it shows that Lenacapavir is likely to be effective against HIV strains that circulate in East Africa.”
Since the 1990s, HIV drug combinations aimed at different steps in the virus life cycle have been able to reduce virus load in patients to almost undetectable levels. But drug resistance is a growing concern since the virus has developed ways to frustrate existing therapies. Lenacapavir, however, is the first medication to interrupt the protective capsid layer that surrounds the genetic material (RNA) of HIV, blocking the virus’s ability to reproduce and transmit from person to person.
The treatment twice a year with Lenacapavir has been effective in patients who have never been treated and those with HIV strains that are resistant to other medications. Last year, clinical trials showed that Lenacapavir’s injections were 100% effective to prevent HIV infection among women in sub -Saharan Africa, which were negative HIV.
However, there was little information available on pre-existent resistance to Lenacapavir in HIV-1 strains less well studied such as subtype A1 and D, which are more common in the east and southern Africa. Subtype B strains of HIV-1, which predominantly affect Europe and the United States, rarely have pre-existing mutations that would cause resistance to Lenacapavir medications.
Dr. Lee and her colleagues from the University of Science and Technology of Mbarara at the General Hospital of Uganda and Massachusetts in Boston helped fill that void. The capsid proteins of the HIV-1 A1 and D subtypes of 546 Ugandes patients, who had never used antiretroviral therapy were sequenced. This approach allowed researchers to examine the viral variants that circulate naturally.
They discovered that none of the patients had genetic mutations that would lead to greater lenacapavir resistance. Only nine participants had lower Lenacapavir resistance mutations that could partially reduce effectiveness, but not enough to cause total medication resistance.
“Our study supports Lenacapavir’s potential efficacy in this region. As Lenacapavir is implemented in East Africa, additional studies must monitor the appearance of drug resistant strains,” said Dr. Lee. “It is important that we make sure that HIV investigation reaches little studied communities where unique viral strains circulate.”