EFFICACY AND SAFETY OF A SIMPLIFICATION STRATEGY BASED ON DOLUTEGRAVIR AND DARUNAVIR / COBICISTAT VS OPTIMIZED TREATMENT IN SUPPRESSED HIV-1-INFECTED PATIENTS CARRYING ARCHIVED MULTIDRUG RESISTANCE MUTATIONS

• Status: Active, not recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The availability of antiretroviral therapy has led to a reduction in morbidity and mortality in patients with chronic HIV infection. The treatment, however, is not free of side effects, has potential interactions with other medications, is expensive and can be complex, especially in those patients who are very experienced and with mutations that give them resistance to multiple drugs. For this reason, the development of simplification strategies that avoid unnecessary exposure to antiretroviral agents remains of great interest.

This is a simplification study, in which the investigators try to evaluate that with less medication the investigator can maintain the same virological control of the disease. This would mean a lower burden of medication for patients, facilitating its administration and reducing the number of unwanted side effects.

Specifically, the investigators intend to evaluate the treatment with Darunavir / cobicistat plus Dolutegravir as a simplification strategy, since both drugs are taken once a day, have a powerful antiviral activity, even against antiretroviral resistant viruses, and are among the best tolerated (with fewer side effects). The results reported in some observational studies suggest that two-drug therapy (bitherapy) as a simplification strategy could also be safe and effective, however, as far as the investigators know, there are no data and clinical trials that specifically evaluate darunavir / cobicistat plus dolutegravir as a strategy of simplification.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundacio Lluita Contra la SIDA; Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Collaborator: ViiV Healthcare
• Treatments: Cobicistat; Darunavir; Dolutegravir

Criteria

Inclusion Criteria:

1. HIV-1 infected patients (≥18 years).

2. Confirmed plasma HIV-1 RNA levels < 50 copies/ml for ≥ 6 months preceding the study randomization.

3. Currently ART containing at least 3 antiretroviral drugs (protease inhibitors, non- nucleoside reverse transcriptase inhibitors, integrase inhibitors and CCR5 receptor antagonists on routine clinical practice).

4. Must have historical genotyping tests showing DRM associated with at least two antiretroviral classes according to Stanford dB.

5. Willing and able to be adherent to their cART regimen for the duration of the study (in opinion of physician).

6. If heterosexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner*) from 14 days prior to study inclusion and at least 12 weeks after the end of the study; all female volunteers must be willing to undergo urine pregnancy tests at time points specified in the Schedule of Procedures.

7. If heterosexually active male; willing to use an effective method of contraception (anatomical sterility in self) or agree on the use of an effective method of contraception by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility*) from the day of the study inclusion until 12 weeks after the end of the study.

8. Signed informed consent

• condom use nor diaphragma are considered as an additional method of contraception only and cannot be the only method of contraception used as not been considered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.

Exclusion Criteria:

• 1. Subjects with any DRM associated to INSTI (i.e. T66I, 74M, E92Q, T97A, F121Y, E138A/K, G140A/S, Y143R/H/C, S147G, Q148H/K/R, N155H AND R263K) in historical genotyping tests. 2. Subjects with any evidence of previous virologic failure to INSTI-based regimens (with or without DRM in the integrase). 3. Subjects who have experienced previous uncontrolled interruptions of INSTI-based regimens. 4. Subjects who have archived DRM conferring a low - or higher - level of resistance to DRV/cobi (>15 points from Stanford dB score). 5. Subjects with unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones) 6. Subjects with severe hepatic impairment (class C) according to the Child-Pugh classification 7. Subjects with alanine aminotransferase (ALT) ≥ 5 times upper normal limit (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN. 8. Subjects with hepatitis C co-infection that would require therapy during the study.

9. Subjects with hepatitis B surface antigen (HBsAg) positive. 10. Known allergy to the study drugs or their components. 11. Current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study. 12. Females who are pregnant or breastfeeding