safety and efficacy of a switch to doravirine, tenofovir, lamivudine (mk-1439a) in human immunodeficiency virus (hiv-1)-infected participants virologically suppressed on an anti-retroviral regimen in combination with two nucleoside reverse transcriptase inhibitors (mk-1439a-024)

Conditions: HIV-1 Infection

Summary: the multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to mk-1439a (mk-1439 \[doravirine\] plus lamivudine and tenofovir disoproxil fumarate) in hiv-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. the primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at screening for 24 weeks, as assessed by the proportion of participants maintaining hiv-1 ribonucleic acid (rna) \<50 copies/ml. the base study results will be based on the first 48 weeks of this ongoing study.

three optional study extensions are planned. study extension 1 will evaluate safety of the switch to doravirine, tenofovir, lamivudine for an additional 2 years beyond the base study. study extensions 2 and 3 will evaluate safety of the switch to doravirine, tenofovir, lamivudine until doravirine, tenofovir, lamivudine becomes locally available, or 4 years beyond study extension 1, whichever comes first.

Eligibility criteria:
inclusion criteria: inclusion criteria include, but are not limited to: * have plasma human immunodeficiency virus-1 ribonucleic acid (hiv-1 rna) levels below the limit of quantification (bloq) (\<40 copies/ml by the abbott realtime hiv-1 assay as determined by the central laboratory) at the screening visit. * receiving antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a nnrti (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 nucleoside reverse transcriptase inhibitor (nrtis) (and no other antiretroviral therapy) continuously for \>= 6 months. * receiving first or second retroviral regimen (participants receiving a nnrti at screening must be on their first retroviral regimen) * no history of using an experimental nnrti * has a genotype prior to starting his/her initial antiretroviral regimen and no known resistance to any of the study agents * not receiving lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment * has the following laboratory values at screening within 30 days prior to the treatment phase of this study: alkaline phosphatase ≤ 3.0 x upper limit of normal (uln), serum aspartate aminotransferase (ast) and serum alanine aminotransferase (alt) ≤ 5.0 x uln, and hemoglobin ≥9.0 g/dl (if female) or ≥10.0 g/dl (if male) * has a calculated creatinine clearance at the time of screening ≥ 50 ml/min, based on the cockcroft-gault equation * male or female participant not of reproductive potential or, if of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: 1) practice abstinence from heterosexual activity, or 2) use acceptable contraception during heterosexual activity * for inclusion in study extension 1 (optional): completed the week 48 visit; considered to have derived benefit from study participation up to week 48; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug * for inclusion in study extension 2 (optional): completed the week 144 visit; considered to have derived benefit from study participation up to week 144; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug * for inclusion in study extension 3 (optional): completed the week 240 visit; considered to have derived benefit from study participation up to week 240; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug exclusion criteria: exclusion criteria include, but are not limited to: * uses recreational or illicit drugs or has a recent history of drug or alcohol abuse or dependence * received treatment for a viral infection other than hiv-1, such as hepatitis b, with an agent that is active against hiv-1 such as adefovir, emtricitabine, lamivudine, or tenofovir * has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir * participated in a study with an investigational compound or device within 30 days or anticipates doing so during the course of this study * used systemic immunosuppressive therapy or immune modulators within 30 days or anticipates needing them during the course of this study (short courses of corticosteroids will be allowed) * current, active diagnosis of acute hepatitis due to any cause (participants with chronic hepatitis b and c may enter the study as long as they fulfill all entry criteria, have stable liver function tests, and have no significant impairment of hepatic function) * has evidence of decompensated liver disease or has liver cirrhosis and a child-pugh class c score or pugh-turcotte score \>9 * pregnant, breastfeeding, or expecting to conceive at any time during the study * female and is expecting to donate eggs or male and is expecting to donate sperm during the study