Efficacy and Safety of 2 Raltegravir Doses in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

Condition(s) targeted: HIV Infections; Tuberculosis

Intervention: efavirenz (Drug); raltegravir (Drug); raltegravir (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: French National Agency for Research on AIDS and Viral Hepatitis

Official(s) and/or principal investigator(s):
Beatriz Grinsztejn, MD, Study Chair, Affiliation: Fiocruz, Rio de Janiero, Brazil
Jean-Michel Molina, MD, Study Chair, Affiliation: Hôpital Saint-Louis, Paris, France

Overall contact:
Jean-Michel Molina, MD, Phone: +33 (0)1 43 49 90 66, Email: jean-michel.molina@sls.aphp.fr

Raltegravir is a potent antiretroviral agent that could be used as an alternative to efavirenz in HIV-1 infected patients with tuberculosis. However due to pharmacokinetic interactions, the optimal dose of raltegravir to be used in combination with rifampin is currently unknown.

This phase II open-label randomized multicenter trial is designed to estimate the antiviral efficacy of two doses of raltegravir and one dose of efavirenz at week 24, in HIV-1 naive patients co-infected with active tuberculosis (TB) treated with rifampin.

Official title: Phase II Open-label Randomized Multicenter Trial to Compare the Efficacy and Safety of Two Different Doses of Raltegravir and Efavirenz, All in Combination With Tenofovir and Lamivudine, in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

Study design: Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Virologic success, using Time to Loss of Virologic Response (TLOVR) algorithm: -Plasma HIV RNA below 50 copies/ml at week 20, confirmed at week 24 -Absence of permanent treatment discontinuation -Absence of death -Still follow-up at week 24

Secondary outcome:

Proportion of patients with virologic response with the following definitions: - Plasma HIV RNA <50 copies/ml at week 24 - Rate of strategy discontinuation and treatment changes - Proportion of death - Proportion of patients loss to follow-up

Proportion of patients with virologic response with the following definitions: o Plasma HIV RNA <50 copies/ml o Plasma HIV RNA <400 copies/ml

Evolution in HIV RNA and HIV DNA (total and 2 LTR circular) from baseline to week 48

Rate of viral resistance mutations in the plasma at the time of virologic failure and in comparison with HIV-RNA mutations at W0

Evolution of CD4 cell counts from baseline to week 48

Frequency, type and time to a new AIDS-defining event or death

Frequency, type, time to grade 3 or 4 adverse event

Rate of success of TB treatment

Anti-TB resistance rate

Evolution of raltegravir and efavirenz trough concentration

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adult patients (at least 18 years old)

- Plasma HIV RNA > 1000 copies/ml

- HIV-1-infection confirmed by ELISA and Western blot or Immunofluorescence

- ART naïve patients or

- ART for less than 3 months and more than 6 months ago ; an HIV resistance genotype at

baseline showing no mutation to NNRTI and TDF or 3TC will be required

- For women of childbearing age, negative urinary test for pregnancy and to accept

contraceptive methods: condom use and intra-uterine device when possible or declare no wish of pregnancy in the coming year.

- Confirmed or probable TB

- TB treatment including rifampin started since 2 to 4 weeks before screening

- Signed informed consent form

- For French patients, to be affiliated to the National Health Care System

Exclusion Criteria:

- HIV-2 infection (single or with HIV-1)

- Woman who is pregnant or likely to become so, is breastfeeding or refuses to use

contraception

- ALT>2. 5N, Hb <7g/dl, neutrophils < 750/mm3, platelet<50 000/mm3, bilirubin >5N,

lipase >3N

- Creatinine clearance <60ml/min as assessed by the Cockcroft method

- Ongoing psychiatric pathology or any condition (including, but not limited to, the

consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol

- Concomitant treatments including phenytoin or phenobarbital (compounds interacting

with UGT1A1)

- Prior TB with a Mycobacterium tuberculosis strain resistant to rifampin

- TB treatment started for more than 4 weeks before screening

Jean-Michel Molina, MD, Phone: +33 (0)1 43 49 90 66, Email: jean-michel.molina@sls.aphp.fr

Hospital Genral de Nova Iguaçu, Nova Iguaçu, Brazil; Not yet recruiting
Pilotto Jose Henrique, MD, Phone: +55 21 26 67 11 71

Hospital Sanatorio Pertenon, Porto Alegre, Brazil; Not yet recruiting
Nemora Barcellos, MD, Phone: +55 51 33 36 14 44

Ipec/Fiocruz, Rio de Janeiro, Brazil; Not yet recruiting
Beatriz Grinsztejn, MD, Phone: +55 21 38 65 95 95, Email: gbeatriz@unisys.com.br

Hospitral Universitario Pr Edgar Santos, Salvador da Bahia, Brazil; Not yet recruiting
Carlos Brites, MS, Phone: +55 21 32 35 49 01

STD/AIDS department, Sao Paulo, Brazil; Not yet recruiting
Denize Lotufo, MD, Phone: +55 11 50 87 98 43

Hôpital Lariboisière, Paris 75010, France; Recruiting
Pierre Sellier, MD, Phone: +33 (0)1 49 95 63 53

Hôpital Saint-Louis, Paris 75010, France; Recruiting
Jean-Michel Molina, MD, Phone: +33 (0)1 42 49 90 66, Email: jean-michel.molina@sls.aphp.fr
Nathalie De Castro, MD, Sub-Investigator

CHI Villeneuve Saint Georges, Villeneuve Saint Georges 94195, France; Recruiting
Olivier Patey, MD, Phone: +33 (0)1 43 86 21 62

Starting date: July 2009
Last updated: February 26, 2010