One Year Follow-Up of Darunavir/Cobicistat Monotherapy in Pretreated HIV Patients

Abstract

IntroductionThe availability of antiretroviral treatment (ART) has made it possible to consider HIV-1 infection as a chronic disease. This has led to a change in the objectives of ART with a greater importance in improving the patient's quality of life and more efficient use of the resources, without compromising the effectiveness of treatments. In ART naive patients, on the first and successive lines after ART failure, preferred regimens remain the combination of three active drugs against HIV: Two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), a protease inhibitor (PI) with a pharmacokinetic (PK) enhancer (booster) (cobicistat or ritonavir), integrase strand transfer inhibitor (INSTI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) [1][2][3].Currently, boosted protease inhibitor monotherapy (PI/r): Darunavir/ritonavir (DRV/r) or Lopinavir/ritonavir (LPV/r) is only contemplated in the main treatment guidelines in pretreated patients to avoid toxicity associated with NRTIs, reduce costs and simplify ART. PI/r monotherapy with Atazanavir/ritonavir (ATV/r) is not recommended because of the worst results obtained in clinical trials. To initiate monotherapy based on PI/r, the patient must meet the following criteria: absence of chronic hepatitis B, plasma HIV-RNA viral load <50 copies/mL for at least 6 months and absence of mutations in the protease gene or virological failures (VF) prior to PI/r. PI/r are drugs that have a high genetic barrier and are used in monotherapy to maintain virological suppression in most patients, but with lower rates than triple therapy. The use of monotherapy with Lopinavir/ritonavir (LPV/r) and Darunavir/ritonavir (DRV/r) is associated with a higher frequency of "blips", defined as isolated and transient viral load values between 50 and <200 copies/mL. The "blips", although in most studies are not related to the increased risk of virological failure, do recommend re-evaluation of ART (degree of adhesion and genetic barrier) and in some patients may select resistant mutants [1]. Virological failure occurs when, in a patient with strict adherence and optimal tolerability to ART, there are any of the following two situations: a) Viral load detectable after 24 weeks of initiation of ART; B) if after reaching undetectability, th e viral load returns to >50 copies/mL in two consecutive determinations (separated by 2-4 weeks), excluding intercurrent vaccinations or infections (they may produce transient elevations of viral load). Virologic a l failure is AbstractIntroduction: Boosted protease inhibitor monotherapy (PI/r ) : Darunavir/ritonavir (DRV/r) or Lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pre-treated HIV patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTIs), reduce costs and simplify antiretroviral treatment. To start PI/r monotherapy, according to GESIDA g uidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, pla...