Early Versus Standard Start of Anti-HIV Therapy for Treatment-Naive Adults in Haiti

HIV Infections Clinical Trial

Official title:

A Randomized Clinical Trial to Determine the Efficacy of Early Versus Standard Antiretroviral Therapy in HIV Infected Adults With CD4+ T Cell Counts Between 200 and 350 Cells/mm3

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00120510
• Other study ID #: CIPRA HT 001
• Secondary ID: 5K24AI051966-031
• Status: Completed
• Phase: N/A
• First received: July 14, 2005
• Last updated: October 13, 2014
• Start date: July 2007
• Est. completion date: September 2009

Study information

• Verified date: October 2014
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Anti-HIV treatment consisting of lamivudine/zidovudine (3TC/ZDV) and efavirenz (EFV) is the current standard of care for initial treatment of HIV in most areas of the world. The purpose of this study is to determine the best time to start this anti-HIV treatment in treatment-naive adults in Haiti.

Description:

In many parts of the world, initial standard of care for HIV includes 3TC/ZDV and the non-nucleoside reverse transcriptase inhibitor EFV. However, it is unclear if early (CD4 count less than 350 cells/mm3) or delayed (CD4 count less than 200 cells/mm3) therapy initiation leads to improved survival. This study will determine the most appropriate time to initiate ART in HIV infected individuals in Haiti. The study will enroll patients from the Haitian Study Group on Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) Centers. Some participants in this study will have active pulmonary tuberculosis (TB).

This study will last at least 3 years. Participants will be randomly assigned to one of two groups at study entry. Group A participants will receive 3TC/ZDV twice daily and EFV once daily at study enrollment. Participants receiving TB therapy at the time of enrollment may be observed for 2 weeks prior to beginning early therapy. Dosage adjustment of EFV may be necessary for participants receiving rifampin as part of their TB therapy. Group B participants will receive 3TC/ZDV twice daily and EFV once daily when they develop clinical AIDS or their CD4 count drops below 200 cells/mm3 (WHO Stage IV). Directly observed therapy will be used for the first two months of treatment for every participant.

Group A participants will have 14 study visits after beginning treatment; the visits will occur at Months 1, 2, 3, and every 3 months thereafter. Medical and medication history, physical exams, and contraceptive counseling for women will occur at all visits. HIV counseling, blood collection, and HIV staging will occur at most visits. At some study visits, Group A participants will be asked to complete quality of life and adherence questionnaires. Group B participants will have 14 study visits after study entry and will begin treatment when they meet WHO criteria. Assessments will be the same as for Group A. Any participant who fails the first-line regimen during the study will switch to a second-line ART regimen.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 816
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-infected

• Received pre- and post-test counseling at the GHESKIO Centers

• CD4 count between 200 and 350 cells/mm3

• World Health Organization (WHO) Stage I, II, or III HIV disease

• Willing to use acceptable forms of contraception

Exclusion Criteria:

• WHO Stage IV HIV disease (AIDS)

• 7 or more days of cumulative ART prior to study entry OR on ART at time of study entry

• Active TB, if diagnostic work-up for TB is incomplete OR if decision to treat TB has not been made. More information on this criterion can be found in the protocol.

• Recurrent active TB OR history of interrupted or incomplete TB therapy. More information on this criterion can be found in the protocol.

• Has not been evaluated for latent TB and decision to treat latent TB with isoniazid has not been made. More information on this criterion can be found in the protocol.

• Requires ART in the next 3 months, in the opinion of the investigator

• Other serious medical illness requiring chronic maintenance therapy (e.g., hypertension, diabetes) UNLESS the individual has completed at least 14 days of therapy prior to study enrollment AND is clinically stable

• Any psychological condition (e.g., severe depression, schizophrenia) that, in the opinion of the investigator, may interfere with the study

• Any social condition (e.g., pending emigration, pending incarceration) that, in the opinion of the investigator, may interfere with the study

• Active drug or alcohol use that, in the opinion of the investigator, may interfere with the study

• Current inflammation of the pancreas

• Allergy/sensitivity to any of study drugs or their formulations

• Requires certain medications

• Enrolled in another therapeutic or interventional clinical trial

• Pregnant or breastfeeding

Study Design

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

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

Drug:
• Efavirenz
Non-nucleoside reverse transcriptase inhibitor dosed at 600mg taken by mouth every 24 hours at bedtime
• Lamivudine/Zidovudine
Nucleoside reverse transcriptase inhibitor dosed at 150mg/300mg fixed dose combination taken by mouth every 12 hours

Locations

Country	Name	City	State
Haiti	Les Centres GHESKIO CIPRA CRS	Port au Prince

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Haiti, 

References & Publications (5)

Blankson JN. Primary HIV-1 infection: to treat or not to treat? AIDS Read. 2005 May;15(5):245-6, 249-51. Review. — View Citation

Duncombe C, Kerr SJ, Ruxrungtham K, Dore GJ, Law MG, Emery S, Lange JM, Phanuphak P, Cooper DA. HIV disease progression in a patient cohort treated via a clinical research network in a resource limited setting. AIDS. 2005 Jan 28;19(2):169-78. — View Citation

Pape JW. Tuberculosis and HIV in the Caribbean: approaches to diagnosis, treatment, and prophylaxis. Top HIV Med. 2004 Dec-2005 Jan;12(5):144-9. Review. — View Citation

Teck R, Ascurra O, Gomani P, Manzi M, Pasulani O, Kusamale J, Salaniponi FM, Humblet P, Nunn P, Scano F, Harries AD, Zachariah R. WHO clinical staging of HIV infection and disease, tuberculosis and eligibility for antiretroviral treatment: relationship to CD4 lymphocyte counts. Int J Tuberc Lung Dis. 2005 Mar;9(3):258-62. — View Citation

Thorner A, Rosenberg E. Early versus delayed antiretroviral therapy in patients with HIV infection : a review of the current guidelines from an immunological perspective. Drugs. 2003;63(13):1325-37. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		At 36 months	No
Secondary	Safety and drug-associated side effects and toxicities of the study drugs		Throughout study	Yes
Secondary	Pattern and frequency of antiretroviral drug resistance during ART		Throughout study	No
Secondary	Occurrence and clinical outcome of opportunistic infections, viral coinfections, and immune reconstitution syndromes observed during ART		Throughout study	No
Secondary	TB treatment outcomes in patients with active pulmonary TB at enrollment		Throughout study	No
Secondary	Quality of life scores based on self-report questionnaires		Throughout study	No
Secondary	Adherence based on self-report questionnaires and dosage count		Throughout study	No
Secondary	Cost of therapy		Throughout study	No
Secondary	Plasma HIV-1 RNA below limits of quantitation after initiating ART		Every 6 months throughout study	No
Secondary	Absolute CD4 cell count change from baseline in subjects who initiate ART		Every 6 months throughout study	No

External Links

•   Click here for information on starting anti-HIV medications
•   Click here for more information on efavirenz
•   Click here for more information on lamivudine/zidovudine
•   Haga clic aquí para ver información sobre este ensayo clínico en español.