Evaluating the Pharmacokinetics, Safety, and Tolerability of Doravirine (MK-1439) and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (MK-1439A) in HIV-1-Infected Children and Adolescents

Inclusion Criteria

• •Weight greater than or equal 35 kg at entry
• •If not of legal age to provide independent informed consent: Parent or guardian was willing and able to provide written informed consent for study participation; in addition, when applicable per local Institutional Review Board / Ethics Committee (IRB/EC) policies and procedures, potential participant was willing and able to provide written informed assent for study participation. If of legal age to provide independent informed consent as determined by site Standard Operating Procedures (SOPs) and consistent with site IRB/EC policies and procedures: Potential participant was willing and able to provide written informed consent for study participation
• •Confirmed HIV-1-infection based on documented testing of two samples collected at different time points. More information on this criterion can be found in the protocol.
• •Antiretroviral therapy (ART) exposure, virologic suppression, and resistance requirements, as follows:
• •Cohort 1
• •ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records:
• •At entry, receiving combination ART with raltegravir (RAL) or dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs); AND
• •At entry, had not received non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitor (PIs), or cobicistat within the previous 30 days; AND
• •Virologic suppression, as documented in medical records and as defined by:
• •One or more HIV RNA polymerase chain reaction (PCR) result below the level of quantification (BLLQ) within 15 months prior to enrollment, AND
• •If any HIV RNA PCR tests had been done within 3 months prior to enrollment, all results were below the level of quantification, AND
• •HIV RNA PCR result less than 40 copies/mL at screening, performed as per the protocol.
• •Cohort 2 ART-naive
• •ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records:
• •At entry, received no antiretrovirals (ARVs) for treatment of HIV infection including investigational agents (prior receipt of ARVs for prevention of perinatal transmission was permitted); AND
• •Screening genotypic resistance test results indicated susceptibility to doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) (see the protocol for more information; result must be available prior to enrollment), performed as per the protocol; AND
• •If available, as documented in medical records, any prior genotypic resistance test result indicated susceptibility to DOR, TDF, and 3TC (see the protocol for more information).
• •Note: For individuals that were re-screened, the genotypic resistance test did not need to be repeated.
• •Cohort 2 ART-experienced
• •ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records:
• •No previous history of change in ARVs due to clinical or virologic failure, in the opinion of the site investigator or designee; AND
• •Virologic suppression, as documented in medical record and as defined by:
• •One or more HIV RNA PCR result BLLQ within 15 months prior to enrollment, AND
• •If any HIV RNA PCR tests had been done within 3 months prior to enrollment, all results were below the level of quantification, AND
• •HIV RNA PCR result less than 40 copies/mL at screening (see the protocol for more information); AND
• •If available, as documented in medical records, any prior genotypic resistance test result indicated susceptibility to DOR, TDF, and 3TC (see the protocol for more information).
• •Note: This group of ARV-experienced, virologically suppressed participants were only enrolled once there was data from the adult switch studies indicating virologic efficacy and safety (see the protocol for more information). Sites were informed via a Clarification Memorandum when ART-experienced participants could be enrolled. A single, unconfirmed HIV-1 RNA result greater than or equal to the level of quantification but less than 500 copies/mL, between 3 and 15 months, prior to enrollment was not exclusionary as long as the other criteria for documentation of virologic suppression were met.
• •Grade 2 or lower hemoglobin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, and lipase on specimens obtained at screening
• •For Cohort 2 only, grade 2 or lower creatinine, proteinuria, and glycosuria on specimens obtained at screening
• •Estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min/1.73 m\^2, on specimens obtained at screening, based on the Schwartz equation. More information on this criterion can be found in the protocol.
• •For females who had reached menarche or who were engaging in sexual activity (self-reported), negative pregnancy test at entry
• •For females engaging in sexual activity that could lead to pregnancy (self-reported), agreed to use two effective, medically accepted birth control methods while on study and for two weeks after permanently discontinuing study drug
• •For males engaging in sexual activity that could lead to pregnancy (self-reported), agreed to use condoms while on study and for two weeks after permanently discontinuing study drug
• •Able and willing to swallow available formulation(s) (tablet or, as available, oral granules).