Do HIV drug tests need better infectious testing?

An extended trial protocol helped reclassify HIV infections as baseline infections in a randomized trial involving patients using long-term cabotegravir as injectable prophylaxis (PrEP), a researcher said .

In post-hoc studies, intra-arm cabotegravir annual HIV incidence of HPTN 083 decreased to 0.37 from 0.41, and the risk ratio decreased from 0.34 to 0.32, Raphael Landovitz, MD, University of California Los Angeles , and colleagues.

Notably, extended trials did not reveal any changes in the arm tenofovir / emtricitabine (Truvada), with 39 episodic infections, almost all as a result of suboptimal retention or lack of drug monitoring.

The Landovitz group conducted a post-hoc analysis of the stage IIb / III test presented at the International AIDS Conference in July 2020, and shared their findings at a late break session at the Virtual Conference on Retroviruses and Fair Diseases (CROI). The trial compared PrEP with injectable cabotegravir versus daily oral PrEP among HIV-negative men who have sex with men (MSM) and transgender women. At the time, Landovitz reported 13 incident infections in the cabotegravir arm and two baseline infections. The review was suspended early due to exceeding the jurisdictional limit.

Landovitz said inaccurate results in a standard HIV test algorithm within the test yielded an additional test based on nuclear acid at sites, which led to a retrospective test of stored samples. The post-hoc study found that one of the incident diseases was a baseline disease, and identified another baseline disease, resulting in 12 incident diseases and four baseline diseases.

“The rate of viremia was often low at the first positive HIV visit and there was often a long period of low-level viremia or viral suppression after infection,” Landovitz said.

For the open-label part of the test, he said, they are currently investigating the use of viral load testing as a primary screening for HIV infection, and oral lead will also be optional. The standard screening algorithm included a real-time point-of-care antibody test and an antigen antibody test at each visit, including a mandatory negative RNA test within 14 days of enrollment.

During a question and answer session, Landovitz pointed out that this was a test case, as the currently available diagnoses are less sensitive than nuclear acid-based tests.

“This is a call to action for the rapid development of a more sensitive, potentially diagnostic, affordable, implementable diagnostic that recognizes HIV infections at earlier stages than the algorithms Our routine diagnostics are doing, “he said, adding that this could have an impact on other long – term antivirals currently under development.

Revised classification resulted in Landovitz and colleagues being classified into four groups: baseline diseases before any study result (four diseases), diseases that occurred when a patient had prolonged hiatus since the last administration of cabotegravir at the time of detection (five diseases), diseases where they were detected at the oral lead level (three diseases), and diseases identified despite on-time cabotegravir injection (four diseases).

Interestingly, when groups examined these cases, all four identified cases had evidence despite adherence to cabotegravir for testing positive for HIV weeks earlier than the time of detection. on the site.

Evaluation of the immune linkages is ongoing, but long-acting cabotegravir can delay the detection of infection using standard HIV testing algorithms, Landovitz said. But he also highlighted some of the potential disadvantages of using a more sensitive diagnosis for early detection of a disease, noting that an over-sensitive diagnosis can “lead the way. is not resource efficient and causes more distress to consumers and suppliers due to waiting times for test results. “