infectious diseases
Antiretroviral Treatment of HIV Infection
Drug interactions
Interactions between antiretrovirals may increase or decrease efficacy. For example, efficacy can be increased by combining a subtherapeutic dose ofritonavir(100 mg once/day) with another protease inhibitor (PI) (eg,darunavir,atazanavir).Ritonavirinhibits the hepatic enzyme that metabolizes the other PI. By slowing clearance of the therapeutically dosed PI,ritonavirincreases the other drug’s levels, maintains the increased levels longer, decreases the dosing interval, and increases efficacy. Another example islamivudine(3TC) pluszidovudine(ZDV). Use of either drug as monotherapy quickly results in resistance, but the mutation that produces resistance in response to 3TC increases the susceptibility of HIV to ZDV. Thus, when used together, they are synergistic. Conversely, interactions between antiretrovirals may decrease the efficacy of each drug. But, these combinations are rarely used in clinical practice anymore (eg, ZDV andstavudine[d4T]). Combining drugs often increases the risk that either drug will have an adverse effect. Possible mechanisms include the following: Hepatic metabolism of PIs by cytochrome P-450: The result is decreased metabolism (and increased levels) of other drugs. Additive toxicities: For example, combining first-generation NRTIs, such asstavudine(d4T) anddidanosine(ddI), increases the chance of adverse metabolic effects and peripheral neuropathy. Also, using atenofovir disoproxil fumaratein aritonavir-boosted regimen increases the plasma levels of tenofovir disoproxil and, in susceptible patients with certain comorbidities, causes renal dysfunction. Many drugs may interfere with antiretrovirals. Coformulated bictegravir is contraindicated when coadministering with a tuberculosis treatment containingrifampinorrifabutin. The levels of bictegravir fall too much due to the presence of inducer effect ofrifampin/rifabutinand predispose to the risk of HIV viral failure (seeGuidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug-Drug Interactions); thus, interactions should always be checked before any new drug is started. In addition to drug interactions, the following influence activity of some antiretroviral drugs and should be avoided: Grapefruit juice, which inhibits an enzyme in the gastrointestinal tract that degrades the PIsaquinavirand thus increases bioavailability ofsaquinavir St. John’s Wort , which can enhance metabolism of PIs and NNRTIs and thus decrease plasma PI and NNRTI levels 