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Disulfiram not successful at reducing latent HIV reservoir
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The drug disulfiram did not reduce the size of the latent reservoir of HIV in CD4 cells in patients receiving antiretroviral therapy, according to researchers from University of Utah, Johns Hopkins University and University of California, San Francisco.
“Disulfiram was safe and well-tolerated, but did not appear to significantly perturb the latent reservoir,” the researchers wrote. “The apparent exposure-response effect observed in this study highlights significant inter-subject variability in disulfiram pharmacokinetics and suggests that higher doses of disulfiram might be more effective.”
According to the researchers, disulfiram, an anti-alcoholism drug, has demonstrated ability to induce HIV-1 transcription in latently-infected CD4 cells in vitro at concentrations achieved in vivo. The researchers conducted a pilot study in which patients on ART with suppressed viremia received 500 mg of disulfiram daily for 14 days.
The single-arm study included 16 participants. Disulfiram was safe and well-tolerated. One patient had a single detectable viral load at one timepoint, but returned to an undetectable load at the next visit. The other 15 patients had undetectable viral loads for the study duration. The size of the latent reservoir was measured 2 weeks before and 10 weeks after receiving disulfiram.
At 10 weeks after treatment, there was no significant change in the size of the viral reservoir. While receiving disulfiram, the residual viremia did not change compared to baseline. Viremia was 1.93-fold higher post-disulfiram than it was at baseline (95% CI, 1.04-3.45). In a post-hoc analysis, there was a rapid and transient viremia increase among individuals with an immediate post-dose sampling. Viremia increased 2.96-fold (95% CI, 1.29-6.81).
“The stability of this latent reservoir is the major barrier to eradication of HIV-1, requiring patients to remain on ART indefinitely,” the researchers wrote. “Given the concern for adverse effects of ART, as well as the financial burden of treatment and need for adherence, strategies to eliminate the latent reservoir have become an urgent research priority.”
Disclosure: The researchers report no relevant financial disclosures.
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