Clinical trial NCT00851630: Tuberculosis and Human Immunodeficiency Virus (HIV) Immune Reconstitution Syndrome Trial (THIRST)
Official title: A Pilot Study Of Open-Label Fixed Dose Combination Zidovudine/Lamivudine/Abacavir In HIV-Infected Persons With Tuberculosis In Moshi, Tanzania; Tuberculosis And HIV Immune Reconstitution Syndrome Trial (THIRST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Tuberculosis
Keywords: HIV
Tuberculosis
Treatment Naive
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Kilimanjaro Christian Medical Centre, Tanzania
name: Kibongoto National Tuberculosis Hospital, Tanzania
name: GlaxoSmithKline
First posted: 2009-02-26
Enrollment: 70
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is twofold: (1) to assess the feasibility and safety of fixed dose combination zidovudine/lamivudine/abacavir in HIV infected subjects with tuberculosis in a resource-limited setting, and (2) to assess the impact of delayed versus early initiation strategies for fixed dose combination zidovudine/lamivudine/abacavir on the rate of tuberculosis-associated immune reconstitution inflammatory syndromes.


Eligibility criteria: Inclusion Criteria:

* HIV Infection is documented by rapid HIV test or any licensed enzyme-linked immunosorbent assay (ELISA) test kit and confirmed with a different sample.
* Men or women admitted to Kibongoto or Marangu Hospitals with (a) recent (within 56 days) smear positive tuberculosis (pulmonary or extrapulmonary,) (b)total lymphocyte count \<1,200/mm3, and (c) less than 14 days of antituberculous therapy.
* Antiretroviral naive with the exception of regimens used to prevent mother-to-infant transmission of HIV during pregnancy.
* The following laboratory values obtained within 45 days prior to study entry: absolute neutrophil count (ANC) \>=700/mm³, hemoglobin \> 8 g/dL in women; \>9 g/dL in men, serum creatinine \<= 1.5 times upper limits of normal, AST \<5 times upper limits of normal.
* For all women of reproductive potential (who have not reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation), a negative urine pregnancy test within 48 hours of to study.
* All subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate) and if participating in sexual activity that could lead to pregnancy, the female subject/male partner must use condoms (male or female) without a spermicidal agent.
* Not intending to relocate out of area for the duration of study participation.
* Willingness of subject to adhere to follow up schedule.
* Men and women \>= age 13.
* Ability and willingness of subject or legal guardian/representative to give written consent.

Exclusion Criteria:

* Serious illness, other than tuberculosis, that requires systematic treatment and/or hospitalization, until either completion of therapy or clinical stability on therapy in the opinion of the investigator for at least 14 days prior to study entry. Oral and vaginal candidiasis, mucocutaneous herpes simples, and other illnesses which are minor in the opinion of the site investigator are exceptions
* Diagnosis of or suspicion of tuberculosis of the central nervous system.
* \> 14 days of antituberculous therapy prior to screening.
* \> 28 days of antituberculous therapy for active tuberculosis within the 6 months prior to screening.
* Recent past (within 28 days of study entry) or planned use of corticosteroids.
* Any condition that in the opinion of the investigator would compromise the subject's ability to participate in the study.
* Radiation or systemic chemotherapy within 45 days of entry.
* Any immunomodulator, HIV vaccine, or other investigational therapy within 30 days prior to study entry.
* Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
* Allergy/sensitivity to any study drugs or their formulations.

Primary outcomes:
measure: Number of Serious Adverse Events (SAEs)
timeFrame: 104 weeks
measure: Tuberculosis-immune Reconstitution Inflammatory Syndrome Events
timeFrame: 104 weeks
Secondary outcomes:
measure: Plasma HIV Ribonucleic Acid (RNA) Level < 400 Copies/ml
timeFrame: 104 Weeks
measure: HIV RNA Level < 50 Copies/ml
timeFrame: 104 Weeks
Other outcomes:
Locations:
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical Centre
Study officials:
affiliation: Duke University
name: Nathan M Thielman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shao HJ, Crump JA, Ramadhani HO, Uiso LO, Ole-Nguyaine S, Moon AM, Kiwera RA, Woods CW, Shao JF, Bartlett JA, Thielman NM. Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania. AIDS Res Hum Retroviruses. 2009 Dec;25(12):1277-85. doi: 10.1089/aid.2009.0100.