HIV: Failed viral suppression in CAB/RPV linked to 3 Risk Factors

A body mass index (BMI) ≥30 kg/m², rilpivirine resistance–associated mutations, and the HIV-1 subtype A6/A1 can raise a person’s risk for confirmed virologic failure (CVF) of long-acting cabotegravir (CAB) and rilpivirine (RPV) therapy, new research suggests. A combination of at least two of these factors was necessary to increase risk.

Long-acting CAB/RPV (Cabenuva) is a US Food and Drug Administration–approved antiretroviral therapy that is administered intramuscularly on a monthly basis. Although CVF was rare in all three clinical trials of the drug regimen, understanding the factors that may predispose patients to this outcome is necessary, the authors write. “This information will help inform clinicians and patients,” they say, “allowing them to assess the potential benefits and risks of this novel long-acting therapy.” The results were published July 15 in AIDS.

In the study, researchers pooled the clinical data from the FLAIR, ATLAS, and ATLAS-2M trials for long-acting CAB/RPV. Using these data, they examined whether participant factors such as sex, body weight, resistance mutations, and dosing regimen influenced risk for CVF using a multivariable analysis.

Of the 1039 participants included in the analysis, 13 (1.3%) experienced CVF; 272 participants (26%) in the study population had at least one of the three risk factors, but no single variable raised risk on its own.

Dr Bill Spreen

“When we looked at the presence of only one baseline factor, it was no different than having no baseline factors,” Bill Spreen, PharmD, an author of the study, told Medscape Medical News. Spreen is the medicine development leader for cabotegravir at ViiV Healthcare, in Research Triangle Park, North Carolina. CVF rates for participants with no risk factors and those with only one risk factor were 0.4%.

In comparison, CVF occurred in 9 of the 35 participants (25.7%) who had at least two risk factors, and the one participant who had all three risk factors also experienced CVF. The HIV subtype A1/A6, a subtype largely limited to Russia, together with a BMI >30 was the most common combination, occurring in 21 individuals. Ten participants had both RPV resistance mutations and a BMI >30, and only three had HIV subtype A1/A6 and RPV resistance mutations.

“The higher the BMI, typically, the lower the absorption rate of the drug, so it was not surprising to see that come out,” Spreen said. Previous research has associated subtype A1/A6 with L74I polymorphism, which may lower the barrier to resistance to integrase strand transfer inhibitors such as CAB. In the current study, researchers found that the L74I polymorphism mutation was not associated with CVF, in particular among those individuals with non-A1/A6 subtypes.

Dr Susan Swindells

Although A1/A6 was the most common risk factor in the study, testing patients for the subtype prior to initiating CAB/RPV is likely unnecessary in the United States, where the subtype is very rare, Susan Swindells, MBBS, an expert in HIV/AIDS therapeutics from the University of Nebraska Medical Center, Omaha, Nebraska, told Medscape. Swindells was not an author of this study but was involved in all three CAB/RPV clinical trials. The most common risk factors healthcare professionals will likely encounter are high BMI and resistance mutations, she said.

In cases in which a patient may have both a high BMI and resistance mutations, Swindells would not recommend starting a CAB/RPV regimen “unless there was a very pressing reason to do it,” as, for example, in rare cases in which a patient can’t take medications orally. “It’s all a question of balancing the risk and benefit,” she said.

AIDS. Published July 15, 2021. Full text

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