HIV Infections
Conditions
Keywords
HIV, INTEGRASE INHIBITOR, Inhibitor on the lymphoid reservoir, Residual HIV replication, treatment experienced
Brief summary
To determine the efficacy of adding Isentress®, with or without Celsentri®, to effective conventional antiretroviral therapy (comprising at least 2 reverse transcriptase inhibitors and one boosted protease inhibitor), on residual HIV replication and blood cell and gut-associated lymphoid tissue reservoirs (reverse transcriptase inhibitors: RTIs, boosted protease inhibitors: PI/r). To evaluate the effect of therapy intensification by means of an integrase inhibitor with or without CCR5 inhibitor treatment on the lymphoid reservoir in patients chronically infected with HIV-1, successfully treated with conventional triple therapy, measured by: * residual plasma replication between 0 and 50 copies/ml * intracellular HIV RNA levels in circulating lymphocytes (PBMC) and lymphocytes in gut-associated rectal lymphoid tissue (RL). * proviral HIV DNA levels in PBMC and RL.
Interventions
DRUGIsentress®
P.O, 1 tablet containing 400 mg every 12 hours
DRUGCelsentri®
p.o.: 1 tablet containing 150 mg morning and evening (due to combination with PI/r) or containing 300 mg if fosamprenavir/r is used as the PI (MA)
Sponsors
Merck Sharp & Dohme LLC
Abbott
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients, aged over 18 years * HIV infection confirmed by Western Blot * Karnofsky score \> 80% * Treatment-experienced patients having received combined antiretroviral therapy including at least 2 RTI and 1 PI/r for at least 12 months with plasma viral load \<50 copies/ml for at least 6 months * Stable first-line treatment (or other, if changes were not made for reasons relating to viral resistance) with 2 RTIs and 1 PI/r * Proper safety and compliance for the ongoing combination; * Patient agreeing to undergo 3 proctosigmoidoscopy examinations over a 12-month period; * Plasma HIV-1 RNA \<50 copies/ml at inclusion; * Circulating CD4 \>200/mm3 at inclusion; * Isentress® and Celsentri®-naïve patients * No contraindications to the use of the investigational products * Written, informed consent, obtained from the patient or his/her legal representative.
Exclusion criteria
1. Opportunistic infection or active tumor disease 2. Chronic diarrhea, malabsorption, progressive enteric infection 3. Aged under 18 years 4. Pregnancy - breast-feeding ( a pregnancy test will be done at the inclusion visit) 5. Co-infection with HIV-2 6. History of immunomodulator treatment (interleukin-2, alpha-interferon) 7. Ongoing treatment of HBV or HCV co-infection 8. Blood constitution disorders 9. Contraindications to the administration of raltegravir or maraviroc 10. Circulating CD4 nadir \<100/mm3 in the natural history of HIV-1 infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| residual plasma replication between 0 and 50 copies/ml | one year |
| intracellular HIV RNA levels in circulating lymphocytes (PBMC) and lymphocytes in gut-associated rectal lymphoid tissue (RL | one year |
| proviral HIV DNA levels in PBMC and RL | one year |
Secondary
| Measure | Time frame |
|---|---|
| CD4 counts | one year |
| CD8 activation levels | one year |
Countries
France
Outcome results
None listed