Correct answer to Thursdays #USMLE-style question is D! See explanation below. Any questions? Ask and well answer! D) Antiretroviral treatment regimens for the vast majority of treatment-naïve patients are composed of a backbone consisting of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), in combination with a third agent. Other NRTI combinations used as backbones include abacavir-lamivudine and zidovudine-lamivudine. Options for third agents include a non-nucleoside reverse transcriptase inhibitor (NNRTI), a boosted protease inhibitor (PI), or an integrase strand transfer inhibitor (INSTI). The mechanism of action: “binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins” describes that of a PI which is an appropriate third agent for this patient. Examples of PIs include: atazanavir and darunavir. Most PIs as well as the INSTI elvitegravir are administered in combination with another agent (e.g. low dose ritonavir). These agents boost the potency of the PI often by increasing peak or trough concentrations. NNRTIs prevent RNA dependent DNA polymerase (aka reverse transcriptase) from adding new nucleotides to the growing DNA chain thus preventing DNA chain elongation and viral replication. Examples of NNRTIs include: efavirenz, rilpivirine, and nevirapine. INSTIs prevent the integration of viral DNA into the host cell DNA. Examples of INSTIs include: raltegravir and elvitegravir. Explanation of incorrect answers: A) This describes the mechanism of action of nucleoside/nucleotide reverse transcriptase inhibitors, e.g. tenofovir, which this patient has already been prescribed. B) This describes the mechanism of action of the CCR5 antagonist e.g. maraviroc. It is not recommended for patients initiating antiretroviral treatment since it requires an expensive test for tropism prior to initiation and twice-daily dosing. C) This describes the mechanism of action of a fusion inhibitor eg. enfurvitide. Because of toxicity and difficulties in drug administration it is not recommended for treatment naive patients. E) This described the mechanism of action of sulfamethoxazole. Trimethoprim-sulfamethoxazole is a medication frequently prescribed to individuals with HIV or other immunodeficiencies to prevent infection with Pneumocystis jirovecii (previously named Pneumocystis carinii). It is not however an antiretroviral medication. firecracker.me
Posted on: Fri, 25 Jul 2014 16:22:45 +0000