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Current Research

Scientific Overview


Martin Markowitz
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Martin Markowitz, M.D.
Professor, Clinical Director
Combination antiretroviral therapy for the treatment of HIV infection has resulted in the metamorphosis of HIV-1 infection from a near uniformly fatal infection to one that is chronic and manageable with a now widely commercially available variety of simple and well tolerated treatment regimens. As such, the research focus of the Markowitz Lab has shifted from treatment to prevention.

It was a natural extension for our group to bring our expertise in the area of antiretroviral therapy into the prevention arena given documented success of daily oral fixed dose combination tenofovir disoproxil fumarate/emtricitabine (Truvada) as pre-exposure prophylaxis in individuals at high risk of contracting HIV infection. However, the results of clinical trials and demonstration projects suggest that though highly effective when individuals are adherent to treatment, not all high-risk individuals can adhere to the requisite treatment regimen. Our emphasis has been to search antiviral agents with promise as PrEP agents that may be good alternatives to daily oral therapy. Along these lines we have been working on two- the long acting long acting injectable cabotegravir (CAB LA), a novel inhibitor of HIV-1 integrase and MK-8591 aka EFdA (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine), a nucleoside reverse transcriptase translocation inhibitor.

CAB LA has entered the clinic and is in Phase 3 clinical trials being conducted by the HIV Prevention Trials Network. To complement the global development plan, Dr. Markowitz and colleagues have worked in close collaboration with GlaxoSmithKline to develop a China CAB LA Program which will test the efficacy of CAB LA in high risk men who have sex with men and transgender women.

Studies with EFdA, aka MK-8591, remain preclinical. To date we have established 100% protection of a 3.9mg/kg weekly oral dose of MK-8591 against low dose rectal challenge with a recombinant simian/human immunodeficiency virus. Additional studies are being conducted at lower doses of MK-8591 to identify minimal drug concentrations at which protection may be maintained. It is anticipated that this compound may be amenable to administration via an implantable device capable of delivering therapeutic levels of drug over a prolonged period.

Future projects being considered include optimization of long acting combination antiviral therapy in the non-human primate model to facilitate HIV cure research as well as applying novel agents to understand remaining questions surrounding drug penetration in tissue and the possibility of ongoing viral replication despite apparently suppressive cART- an ongoing and important controversy in the field.