Anti-HIV Treatment Interruptions in HIV Infected Adults in South Africa

HIV Infections Clinical Trial

Official title:

A Randomized Clinical Trial Assessing Continuous HAART Versus Interrupted HAART in a Resource Poor Clinic

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00100646
• Other study ID #: 1R01AI051986-01A2
• Secondary ID: R01AI051986Proto
• Status: Completed
• Phase: N/A
• First received: January 4, 2005
• Last updated: August 26, 2014
• Start date: March 2007
• Est. completion date: March 2010

Study information

• Verified date: November 2013
• Source: The Wistar Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

HIV infected people often must take anti-HIV drugs for long periods, leading to long-term drug exposure and toxicity. Interruptions in anti-HIV therapy, also known as structured treatment interruptions (STIs), may have few negative health effects and may be helpful to the overall long-term health of HIV-infected people. The purpose of this study is to determine if sequential short-term STIs of antiretroviral therapy (ART) in HIV infected individuals in a resource-constrained environment can retain the immune reconstitution benefits of continuous treatment while potentially lessening rates of toxicity associated with continuous therapy strategies and at the same time, lessen costs associated with ART.

Description:

Long-term toxicity and the high cost of medications are two problems faced by HIV infected people taking ART. Previous studies in HIV-infected patients suggest that ART with STIs may decrease drug exposure and lessen long-term drug toxicity, while not sacrificing viral suppression and patient health. This study will determine if ART with STIs can maintain the same level of immune function in HIV-infected people as continuous ART. This study will recruit patients in South Africa.

This study will last 3.5 years. At study entry, all participants will begin daily ART consisting of lamivudine, lopinavir/ritonavir, and stavudine. At Month 6, only participants who have responded well to ART (CD4 count greater than 450 cells/uL and viral load less than 50 copies/ml at Month 6) will be randomly assigned to one of two groups. Group 1 participants will participate in STIs during therapy, and Group 2 participants will receive continuous therapy. People in Group 1 will have treatment interruptions of 2, 4, and 8 weeks of duration in between 16-week periods of ART. Group 1 participants will re-initiate therapy if their CD4 count drops below 350 cells or evidence of clinical disease progression is present. Group 2 participants will continue taking ART throughout the study.

At screening, participants will undergo medical history assessment, a physical exam, and magnetic resonance imaging (MRI) and dual energy x-ray absorptiometry (DEXA) scans. There will be at least 22 study visits occurring approximately every 8 weeks, each lasting 45 to 60 minutes. At each study visit, participants will be required to bring any remaining pills with them so adherence can be assessed and will undergo medical assessments. Blood collection will occur at nearly all visits. For female participants, urine collection will occur at all visits. Participants will receive rabies vaccinations at Weeks 16, 17, and 22. A visit at Week 92 will include an MRI and participants will receive a rabies vaccine booster.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV infected

• CD4 count of 200 to 350 cells/mm3 within 60 days of starting study treatment

• Antiretroviral naive. Participants who have received antiretrovirals through postexposure prophylaxis or short course therapy to prevent mother-to-child transmission are eligible for this study.

• Willing to adhere to study treatment

• Willing to be followed for the duration of this study

Exclusion Criteria:

• History of AIDS-defining illness (CDC category C). Patients with a history of pulmonary tuberculosis are not excluded.

• Newly diagnosed AIDS-defining opportunistic infection or other condition requiring acute therapy at study entry

• Previous therapy with agents with significant myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic potential within 30 days prior to study entry

• History of immunomodulatory therapy within 4 weeks prior to screening, or cannot abstain from immunomodulators during the study

• Previously received rabies vaccine

• Current alcohol or drug abuse that, in the opinion of the investigator, may interfere with the study

• Diarrhea (more than 6 stools per day for 7 consecutive days) within 30 days prior to study entry

• Active or suspected acute hepatitis within 30 days of study entry

• Bilateral peripheral neuropathy of Grade 2 or higher at screening

• Inability to tolerate oral medication

• Any clinical condition that, in the opinion of the investigator, would interfere with the study

• Pregnancy 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

Intervention

Behavioral:
• Structured treatment interruption
Interruptions in treatment will last 2, 4, and 8 weeks in between 16-week periods of ART

Drug:
• Lamivudine
300 mg tablet taken orally daily
• Lopinavir/Ritonavir
400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily
• Stavudine
Dosage dependent on weight

Biological:
• Rabies de novo antigen
Vaccine injected intramuscularly

Locations

Country	Name	City	State
South Africa	University of the Witwatersrand	Johannesburg

Sponsors (1)

Lead Sponsor	Collaborator
The Wistar Institute

Country where clinical trial is conducted

South Africa, 

References & Publications (9)

Arnedo-Valero M, Garcia F, Gil C, Guila T, Fumero E, Castro P, Blanco JL, Miró JM, Pumarola T, Gatell JM. Risk of selecting de novo drug-resistance mutations during structured treatment interruptions in patients with chronic HIV infection. Clin Infect Dis. 2005 Sep 15;41(6):883-90. Epub 2005 Aug 4. — View Citation

Azzoni L, Crowther NJ, Firnhaber C, Foulkes AS, Yin X, Glencross D, Gross R, Kaplan MD, Papasavvas E, Schulze D, Stevens W, van der Merwe T, Waisberg R, Sanne I, Montaner LJ. Association between HIV replication and serum leptin levels: an observational st — View Citation

Azzoni L, Foulkes AS, Firnhaber C, Yin X, Crowther NJ, Glencross D, Lawrie D, Stevens W, Papasavvas E, Sanne I, Montaner LJ. Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observat — View Citation

Azzoni L, Papasavvas E, Montaner LJ. Lessons learned from HIV treatment interruption: safety, correlates of immune control, and drug sparing. Curr HIV Res. 2003 Jul;1(3):329-42. Review. — View Citation

Firnhaber C, Azzoni L, Foulkes AS, Gross R, Yin X, Van Amsterdam D, Schulze D, Glencross DK, Stevens W, Hunt G, Morris L, Fox L, Sanne I, Montaner LJ. Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) — View Citation

Foulkes AS, Azzoni L, Li X, Johnson MA, Smith C, Mounzer K, Montaner LJ. Prediction based classification for longitudinal biomarkers. Ann Appl Stat. 2010 Sep;4(3):1476-1497. — View Citation

Kumarasamy N, Flanigan TP, Vallabhaneni S, Cecelia AJ, Christybai P, Balakrishnan P, Yepthomi T, Solomon S, Carpenter CC, Mayer KH. A randomised control trial of structured interrupted generic antiretroviral therapy versus continuous therapy in HIV-infected individuals in Southern India. AIDS Care. 2007 Apr;19(4):507-13. — View Citation

Papasavvas E, Grant RM, Sun J, Mackiewicz A, Pistilli M, Gallo C, Kostman JR, Mounzer K, Shull J, Montaner LJ. Lack of persistent drug-resistant mutations evaluated within and between treatment interruptions in chronically HIV-1-infected patients. AIDS. 2003 Nov 7;17(16):2337-43. — View Citation

Papasavvas E, Kostman JR, Mounzer K, Grant RM, Gross R, Gallo C, Azzoni L, Foulkes A, Thiel B, Pistilli M, Mackiewicz A, Shull J, Montaner LJ. Randomized, controlled trial of therapy interruption in chronic HIV-1 infection. PLoS Med. 2004 Dec;1(3):e64. Epub 2004 Dec 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare intermittent ART to continuous therapy by comparing endpoint CD4 counts between Groups 1 and 2		Throughout study	Yes
Primary	Response to rabies vaccination and booster		Weeks 16, 22, and 92	Yes
Secondary	Comparison of treatment-associated toxicity and safety of 2 to 8 weeks of antiretroviral therapy (ART) interruption versus continuous ART		Throughout study	Yes
Secondary	Determine the outcome of immune reconstitution by monitoring changes in T-cell subsets and the ability to maintain cell-mediated responses against various antigens		Before and after intermittent strategy	Yes
Secondary	Viral evolution and genotypic changes that confer drug resistance		During intermittent and continuous treatment	Yes
Secondary	Effect of treatment interruption on cardiovascular adverse experiences risk factors		From Weeks 0 to 144	Yes

External Links

•   Click here for more information about lamivudine
•   Click here for more information about lopinavir/ritonavir
•   Click here for more information about stavudine