Women in Dual With Dolutegravir

NCT05735535 | Unknown Phase 3

• 1 other identifier: 4455
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• HIV-RNA < 50 copies/ml

  Proportion of patients maintaining a HIV-RNA \< 50 copies/ml according to FDA snapshot algorithm at 48 weeks according to an ITT NC = failure approach in which all randomized patients will be included and considered failures independently of the reason they did not complete the follow-up.

  96 weeks

Study Arms (2)

3TC/DTG

EXPERIMENTAL

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

Drug: Antiviral Agents

TDF Regimen

ACTIVE COMPARATOR

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.

Drug: Antiviral Agents

Interventions

Antiviral Agents DRUG

two-drug one-pill once day

3TC/DTG; TDF Regimen

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione PoliclinicoAgostino Gemelli IRCCS

Roma, 00168, Italy

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Antiviral Agents

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: February 21, 2023
• Study Start: October 1, 2023
• Primary Completion: September 15, 2025
• Study Completion: September 15, 2025
• Last Updated: September 13, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)