Cabotegravir sodium

July 23, 2024 -- A single laboratory-based HIV viral load test used by U.S. clinicians who provide people with long-acting, injectable cabotegravir (CAB-LA) HIV pre-exposure prophylaxis (PrEP) did not reliably detect HIV in a multi-country study. In the study, a single positive viral load test was frequently found to be a false positive result. However, a second viral load test with a new blood sample was able to distinguish true positive results from false positive results for all participants whose initial viral load test was positive. The findings were presented at the 2024 International AIDS Conference (AIDS 2024) in Munich, Germany. “We are still learning how to optimize the package of services that accompany long-acting PrEP, including HIV testing,” said Jeanne Marrazzo, M.D., M.P.H., director of the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). “The viral load testing findings observed in this study illuminate performance gaps in the current U.S. HIV testing algorithm for injectable cabotegravir PrEP.” Long-acting, injectable cabotegravir PrEP, known as CAB-LA, is a highly effective HIV prevention method, administered by intramuscular injection every two months. Routine HIV status monitoring is recommended for any form of PrEP to ensure that people can promptly be aware if they acquire HIV while taking PrEP drugs. In the United States, people taking oral PrEP can do this with point-of-care rapid tests and self-tests that detect HIV antibodies, or laboratory-based HIV testing. However, the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) recommend that people starting or taking CAB-LA PrEP receive a laboratory-based viral load test that detects HIV genetic material in the blood. This recommendation was made because CAB-LA can keep HIV antibodies at such low levels following acquisition that they might not be detected on an antibody-based test. To better inform the U.S. CAB-LA PrEP HIV testing algorithm, researchers examined the accuracy of viral load test results in an open-label extension of a large CAB-LA PrEP efficacy study. The open-label study extension followed 2,620 gay, bisexual, and other men who have sex with men as well as transgender women who have sex with men from the original study population. Twenty-nine participants acquired HIV during the study extension. In five of those 29 participants (17.2%), HIV was first identified by an isolated positive viral load test result. Of these five, two had received CAB-LA in the previous six months, while three had not received CAB-LA for more than six months. The remaining 24 participants had multiple positive tests that identified the presence of HIV. Separately, 23 other participants had an isolated positive viral load test result, but 22 were later found to be HIV-negative in confirmatory testing, meaning their initial result was a false positive. One person’s status could not be determined at the time of analysis. These data indicate that a single positive viral load test alone had a 9.1% positive predictive value—that is, a 9.1% chance of being true HIV acquisition rather than a false positive—in study participants whose last CAB-LA injection was within six months, and a 60% positive predictive value in participants whose last CAB-LA injection had been more than six months ago. Notably, the positive predictive value increased to 100% when study participants had a second round of confirmatory viral load testing with a new blood sample, regardless of the timing of their last CAB-LA injection. “A false positive can result in PrEP interruptions that create potential vulnerability to HIV acquisition, and more importantly causes profound psychological distress while a person awaits confirmatory results from a second test,” said study chair Raphael Landovitz, M.D., professor of medicine in the Division of Infectious Diseases at the David Geffen School of Medicine at the University of California, Los Angeles. “These concerns need to be balanced against the anticipated benefits of slightly earlier HIV detection.” Previous analyses from this study showed combinations of two antibody-based tests had positive predictive values of between 83-100% in participants receiving CAB-LA PrEP. According to the authors, these findings help fill evidence gaps about the performance of available HIV testing tools to optimize CAB-LA PrEP implementation and global scale-up. The global NIAID-supported CAB-LA studies continue to inform HIV prevention policy and practice. NIAID supports this open-label extension study with ViiV Healthcare, Gilead Sciences, Inc., and the NIH-funded HIV Prevention Trials Network (HPTN). NIAID and ViiV Healthcare co-fund the trial, which is conducted by the HPTN. ViiV Healthcare and Gilead Sciences, Inc., provide study medications. The NIH National Institute of Mental Health, NIH National Institute on Drug Abuse, NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development collaborate with NIAID on this study. More information about the study, called HPTN 083, is available on ClinicalTrials.gov under identifier NCT02720094 . NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov . Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

The findings come from the HIV Prevention Trials Network (HPTN) 084 open label extension (OLE) study, which evaluated cis-gender women in sub-Saharan Africa who became pregnant while using Apretude for HIV pre-exposure prophylaxis (PrEP). According to ViiV Healthcare, the data showed that Apretude was generally well tolerated among pregnant women and maintained cabotegravir levels above those associated with HIV protection throughout pregnancy. Kimberly Smith, head of research and development at ViiV Healthcare, commented on the findings: “Today’s late-breaking pregnancy safety data from the HPTN 084 open label extension add to the body of evidence for Apretude as a prevention option for women, including those who conceive while on this long-acting regimen. Women continue to tell us they need more options for HIV prevention, which is why we have been focused on studying cabotegravir LA for PrEP in women from the very beginning. We will continue to prioritize their needs, and those of others disproportionately affected by HIV, as part of our ongoing commitment to ending the epidemic.” The new data will be presented at the 25th International AIDS Conference in Munich, Germany, that started on July 22nd finishing on the 26th. Study findings The HPTN 084 OLE included 2,472 participants who were given the option to use either cabotegravir LA for PrEP or daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) tablets. Participants who became pregnant could choose to continue their Apretude regimen throughout pregnancy. Among the 367 confirmed pregnancies in 348 participants, maternal and pregnancy outcomes for those using cabotegravir LA for PrEP were consistent with those using FTC/TDF and aligned with expected background rates. googletag.cmd.push(function () { googletag.display('text-ad1'); }); The incidence of pregnancy-related maternal adverse events was reported as 45.7 per 100 person-years for those using Apretude during pregnancy, 47.1 per 100 person-years for those using Apretude prior to pregnancy, and 37.5 per 100 person-years for those with no exposure to Apretude. Adverse pregnancy outcomes were similar across all groups, with 33% of women using Apretude during pregnancy reporting negative outcomes compared to 38% of those with prior Apretude use and 27% of those with no exposure. Importantly, no maternal deaths were recorded, and none of the women who became pregnant acquired HIV during pregnancy. Pharmacokinetic analysis A sub-study within the HPTN 084 OLE evaluated the pharmacokinetics of cabotegravir in 50 participants who continued using Apretude during pregnancy. The analysis found that cabotegravir concentrations remained above the protective threshold throughout pregnancy. Median concentrations were 2.1 µg/mL before pregnancy, 1.9 µg/mL during pregnancy, and 2.5 µg/mL postpartum. Although cabotegravir levels decreased slightly from the first to the third trimester, they remained within the protective range. Sinead Delany-Moretlwe, MBBCh, Ph.D., DTM&H, HPTN 084 Protocol Chair, and Research Director at Wits RHI, University of the Witwatersrand in Johannesburg, South Africa, emphasized the significance of these findings: “Women of childbearing age in sub-Saharan Africa experience disproportionately higher rates of HIV incidence, making it essential that we study how HIV medicines impact their health and wellbeing during pregnancy. The findings of the HPTN 084 open label extension provide further evidence on the safety and tolerability of cabotegravir LA for PrEP in expectant mothers and their unborn infants while maintaining protective levels against HIV throughout pregnancy. These findings build upon the well-established efficacy of cabotegravir LA for PrEP and provide reassurance for its usage in this particularly vulnerable population.” Broader implications Apretude (cabotegravir LA for PrEP) is approved in several countries, including the US, EU, UK, Canada, Australia, and South Africa, with ongoing submissions to other regulatory agencies. The HPTN 084 trial, funded by the U.S. National Institutes of Health, the Bill & Melinda Gates Foundation, and ViiV Healthcare, highlights the superior efficacy of cabotegravir LA for PrEP over daily oral FTC/TDF in preventing HIV acquisition. The positive data on Apretude use during pregnancy underscores its potential as a safe and effective HIV prevention method for women, including those who become pregnant. ViiV Healthcare's ongoing commitment to addressing the needs of women at risk of HIV is evident through their dedicated research and development efforts.