Women in Dual With Dolutegravir (Woddol4455)

Institute of Hospitalization and Scientific Care (IRCCS)

Status and phase: Not yet enrolling; Phase 3

Conditions: HIV Infections

Treatments: Drug: Antiviral Agents

Study type: Interventional

Funder types: Other

Identifiers

NCT05735535

4455

Details and patient eligibility

About

Strategies for optimizing antiretroviral treatment in virologically suppressed patients are still a major challenge in the field of HIV. These strategies include improving the toxicity and tolerability of drugs in the short and long term, such as replacing toxic agents with safer ones or reducing the number of drugs in the combination. Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV) that is converted intracellularly to the active form, resulting in higher concentrations of TFV diphosphate in circulating lymphocytes than those obtained with tenofovir disoproxil fumarate (TDF). Because of these pharmacokinetic properties, TAF results in 91% lower plasma exposure to TFV. Phase 3 studies have established the virological noninferiority of TAF to TDF, with a lower frequency of renal and bone adverse events. Replacing TDF with TAF may be a safe and effective option to reduce toxicities when switching from one ARV strategy to another and, to date, could represent the optimization of a three-drug regimen. Dolutegravir (DTG) is a potent INSTI that exhibits rapid and potent viral load reduction and a high barrier to resistance.

Enrollment: 290 estimated patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female individuals
• HIV-1 documented infection
• Age > 18 years
• Being on an effective (pVL < 50 copies/ml) three-drug cART regimen containing tenofovir (TAF or TDF) (e.g. TAF/F/E/C; TAF/F/RPV; TDF/F/RPV; TAF/F+PI/C; TDF/F/PI/c; TAF/F+PI/r; TDF/F/PI/r; TAF/F+DTG; TDF/F/DTG; TAF/F+RTG; TDF/F/RTG; TAF/F/BIC) for at least 3 months before the screening. Two consecutive HIV-1 RNA determinations below the determination threshold before enrollment are required
• No known allergy or intolerance to NRTIs, NNRTIs or INSTIs
• Women of childbearing potential will be required to adopt an effective birth control system throughout the study period
• Subjects able to comply with the protocol requirements
• Informed consent signed

Exclusion criteria

• Having failed virologically any previous ART regimen · Evidence of any 3TC (presence of M184V/I or K65R/E/N) or INSTI resistance · Having ever been treated with mono or dual ARV therapies subsequently intensified to three-drug cART regimen
• Pregnancy or breast-feeding or not willing to use effective contraception if they are of child bearing potential
• An active malignancy or OI requiring active treatment (prophylactic regimens are allowed) · HBV infection · A life expectancy < 2 years

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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290 participants in 2 patient groups

3TC/DTG

Experimental group

Description:

·To evaluate efficacy of switching to a two-drug one-pill regimen with DTG/3TC

Treatment:

Drug: Antiviral Agents

TDF Regimen

Active Comparator group

Description:

comparision arm to maintaining the three-drugs regimen in women currently receiving any three-drug regimen containing Tenovofir (TAF or TDF) (e.g. TAF/F/E/C; TAF/F/RPV; TDF/F/RPV; TAF/F+PI/C; TAF/F+PI/r; TDF/F/PI/r; TAF/F+DTG; TDF/F/DTG; TAF/F+RTG; TDF/F/RTG; TAF/F/BIC) who are virologically suppressed.

Treatment:

Drug: Antiviral Agents