Doravirine for Persons With Excessive Weight Gain on Integrase Inhibitors and Tenofovir Alafenamide

  • End date
    Oct 24, 2023
  • participants needed
  • sponsor
    AIDS Clinical Trials Group
Updated on 15 March 2022
hiv test
reverse transcriptase inhibitor
integrase inhibitors
HIV Vaccine
immune globulin
antibody test
hiv-1 rna measurement


The primary purpose of this study is to see if people with HIV who had a significant weight gain after starting INSTI (integrase strand transfer inhibitor)+TAF/FTC (tenofovir alafenamide/emtricitabine) (TAF/3TC (lamivudine)) regimen could either slow their rate of weight gain or lose weight within about 1 year if they switch to a regimen containing doravirine (DOR; a newer, non-nucleoside reverse transcriptase inhibitor medication). The study will also try to see if participants changing from TAF/FTC (or TAF/3TC) to TDF/FTC (or TDF/3TC) will experience less additional weight gain or a reduction in overall body weight at 48 weeks compared to persons continued on an INSTI + TAF/FTC (or TAF/3TC) combination. INSTINs assessed in A5391 include bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL). Additionally, the study will see whether a change in ART can affect things like waist circumference, metabolic and cardiovascular health, fat and lean mass body composition, bone health, and maintenance of virologic suppression. Finally, the study will look at the safety and tolerability of DOR plus either TAF/FTC (or TAF/3TC) versus TDF/FTC (or TDF/3TC).

Condition HIV Infections
Treatment Tenofovir alafenamide/emtricitabine, Integrase strand transfer inhibitors, Doravirine 100 Mg, tenofovir alafenamide/lamivudine, tenofovir disproxil fumarate/emtricitabine, tenofovir disproxil fumarate/lamivudine
Clinical Study IdentifierNCT04636437
SponsorAIDS Clinical Trials Group
Last Modified on15 March 2022


Yes No Not Sure

Inclusion Criteria

Ability and willingness of participant or legal guardian/representative to provide informed consent
HIV-1, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load. If a rapid HIV test or any FDA-approved HIV-1 E/CIA test kit is not available, two HIV-1 RNA values ≥2000 copies/mL at least 24 hours apart may be performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or by any non-US laboratory that is DAIDS Good Clinical Laboratory Practice (GCLP) compliant and, if performing HIV-1 RNA testing, is Virology Quality Assurance (VQA)-certified
NOTE: The term "licensed" refers to a US FDA-approved kit, or for sites located in
countries other than the United States, a kit that has been certified or licensed by an
oversight body within that country and validated internally
World Health Organization (WHO) and CDC (Centers for Disease Control and Prevention)
guidelines mandate that confirmation of the initial test result must use a test that is
different from the one used for the initial assessment. A reactive initial rapid test
should be confirmed by either another type of rapid assay or an E/CIA that is based on a
different antigen preparation and/or different test principle (e.g., indirect versus
Currently, on a BIC (bictegravir), DTG (dolutegravir), or RAL (raltegravir) +TAF/FTC
competitive), or a Western blot or a plasma HIV-1 RNA viral load
(or TAF/3TC) regimen with ≥48 weeks INSTI+TAF/FTC (or TAF/3TC) dosing prior to study
NOTE A: Participants who did not start TAF at the same time as they started an INSTI will
be eligible if they started TAF/FTC (or TAF/3TC) ≥48 weeks prior to study entry
NOTE B: Participants who underwent within-INSTI class substitutions (including from EVG
(elvitegravir) to BIC, DTG, or RAL) will be eligible if substitution occurred ≥24 weeks
prior to study entry
NOTE C: Participants are permitted ART adherence gaps of ≤7 days (i.e., missed doses), with
a maximum of 3 gaps in the 48 weeks prior to study entry
Ability to acquire NRTIs (TAF/FTC or TAF/3TC, and TDF/FTC or TDF/3TC) and INSTI
through usual care for the duration of the study
A BMI ≥27.5 kg/m2 at screening
An unintentional >10% weight gain in the 1-3 years after initiating or switching to
INSTI-based ART and with ≥48 weeks of TAF/FTC (or TAF/3TC) preceding enrollment, as
Agree to adhere to assigned ART during the study period
ascertained from clinical records, with no other medically apparent reason to readily
explain the weight gain (including, but not limited to, concomitant medication use
[e.g., corticosteroids], Cushing's disease, recent prolonged hospitalization, etc.)
in the opinion of the site investigator
No known plans to change or to initiate medications known to be associated with
significant weight changes during study period
At least one HIV-1 RNA level <50 copies/mL (or below the lower limit of HIV-1 RNA
detection available at the site if the lower limit of detection is >50) performed in
the 48 weeks prior (≤48 weeks) to study screening, and at least one HIV-1 RNA level
<50 copies/mL ≥48 weeks prior to study screening, using an FDA-approved assay
performed by any US laboratory that has a CLIA certification or its equivalent, or at
any network-approved non-US laboratory that is VQA certified. HIV-1 RNA values prior
Intrauterine device (IUD)
to the screening visit will be assessed for eligibility by the site and assay dates
Hormone-based contraceptive
and values do not need to be entered on an eCRF
Screening HIV-1 RNA <50 copies/mL (or below the lower limit of HIV-1 RNA detection
NOTE: Participant report of partner sterilization is acceptable
available if the lower limit of detection is >50) performed within 45 days prior to
study entry by any US laboratory that possesses a CLIA certification or its
equivalent, or at any network-approved non-US laboratory that is VQA certified
For participants capable of becoming pregnant, negative serum or urine pregnancy test
within 45 days prior to study entry by any US clinic or laboratory that has a CLIA
certification or its equivalent, or is using a point of care (POC)/ CLIA-waived test
Absolute neutrophil count (ANC) >750 cells/mm3
or at any network-approved non-US laboratory or clinic that operates in accordance
Hemoglobin >10 g/dL for males and >9 g/dL for females (based on sex at birth)
with GCLP and participates in appropriate external quality assurance programs
NOTE: Participants capable of becoming pregnant are defined as individuals who were
Aspartate aminotransferase (AST) (SGOT) <3x ULN
assigned a female sex at birth and of reproductive potential; (i.e., have reached menarche
Alanine aminotransferase (ALT) (SGPT) <3x ULN
and who have not been post-menopausal for at least 24 consecutive months, and have not
undergone surgical sterilization such as hysterectomy, bilateral oophorectomy, tubal
ligation, or salpingectomy). This includes transgender men who could become pregnant if
menstruation were not suppressed. Participant-reported history is acceptable documentation
of menopause
Participants engaging in sexual activity and capable of becoming pregnant must agree
to use contraception while on study drug (approximately 48 weeks) and for 8 weeks
after the end of the study. At least one of the following contraceptive methods must
be used
Partner sterilization (i.e., vasectomy) and is the sole partner for the
Transgender participants who are currently taking hormones must be on a stable hormone
dose for >12 weeks prior to study entry. Transgender participants should not have
active plans to change their hormone regimen or dose during the study period
NOTE: As some transgender participants may also use hormones purchased outside of the
medical system (e.g., street hormones), the medication history should include questions
about the use of these agents
The following laboratory values obtained within 45 days prior to study entry by any US
laboratory that has a CLIA certification or its equivalent, or at any network-approved
non-US laboratory that operates in accordance with GCLP and participates in
appropriate external quality assurance programs
Calculated creatinine clearance ≥50 mL/min as estimated by the CKD-EPI equation
(a calculator is available at

Exclusion Criteria

Anticipated start or cessation of any of the following drugs during study period
Thyroid replacement hormones
NOTE A: Participants currently receiving antipsychotics, antidepressants
NOTE: Routine methamphetamine use is considered >4 days per week
A history of a diagnosis of osteoporosis or osteopenia
Historical or current evidence of the K65R/E/N or M184V/I mutations (for participants
who have undergone HIV-1 genotyping), due to the potential for viral rebound after
switch from an INSTI- to NNRTI-based regimen
Historical or current evidence of major mutations associated with any NNRTI
NOTE: Refer to the IAS-USA 2019 mutations list, including significant substitutions at
positions 100, 101, 103, 106, 138, 179, 181, 188, 190, 221, 225, 227, 230, or 234 [22]
History of prior virologic failure in the opinion of the site investigator. For
example, a confirmed plasma HIV-1 RNA >1000 copies/mL after having achieved viral
Prior exposure to single-dose nevirapine for the prevention of parent-to-child
transmission of HIV
Any history of significant renal toxicity while taking TDF (as determined by site
Currently breast-feeding or pregnant, or intending to become pregnant during the
duration of the study
Antipsychotics (e.g., clozapine, olanzapine, risperidone, etc.) and
antidepressants (tricyclic antidepressants, e.g., amitriptyline, nortriptyline
etc.; selective serotonin reuptake inhibitors, e.g., fluoxetine, paroxetine
sertraline, etc.; and monoamine oxidase inhibitors, e.g., selegiline) associated
with weight gain
Anticonvulsants/mood stabilizers associated with weight gain (e.g., lithium
valproic acid) or weight loss (e.g., topiramate)
Anti-diabetic agents known to cause weight loss (e.g., GLP-1 receptor agonists
such as exenatide, dulaglutide, semaglutide, metformin, and SGLT-2 inhibitors
such as canagliflozin, dapagliflozin, etc.)
anticonvulsants/mood stabilizers, and thyroid replacement hormones with no dose
modifications for at least 12 weeks prior to entry are eligible
NOTE B: Participants currently receiving anti-diabetic agents known to cause weight loss
with no dose modifications for at least 24 weeks prior to entry are eligible
Planning to undergo bariatric surgery or initiate significant dietary or exercise
changes within the study period (e.g., structured weight loss programs such as Weight
Watchers), as determined by participant report
Known allergy/sensitivity or any hypersensitivity to components of study drug or its
Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with ability to adhere to study requirements, or
cessation of routine methamphetamine use within 60 days prior to study entry
Acute or serious illness requiring systemic treatment and/or hospitalization within 30
days prior to entry
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