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

NCT00100646 | Completed DMC

• 4 other identifiers: 1R01AI051986-01A2R01AI051986Protocol 2411209R01 A151986-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections

Keywords

Treatment Interruption; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• To compare intermittent ART to continuous therapy by comparing endpoint CD4 counts between Groups 1 and 2

  Throughout study

• Response to rabies vaccination and booster

  Weeks 16, 22, and 92

Secondary Outcomes (4)

• Comparison of treatment-associated toxicity and safety of 2 to 8 weeks of antiretroviral therapy (ART) interruption versus continuous ART

  Throughout study

• 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

• Viral evolution and genotypic changes that confer drug resistance

  During intermittent and continuous treatment

• Effect of treatment interruption on cardiovascular adverse experiences risk factors

  From Weeks 0 to 144

Study Arms (2)

1

EXPERIMENTAL

Highly active antiretroviral therapy (HAART) consisting of lamivudine, lopinavir/ritonovir, and stavudine for 16 weeks with three structured treatment interruptions for 2, 4, and 8 weeks each; rabies vaccine at Weeks 16, 17, 22 and 92.

Behavioral: Structured treatment interruption; Drug: Lamivudine; Drug: Lopinavir/Ritonavir; Drug: Stavudine; Biological: Rabies de novo antigen

2

ACTIVE COMPARATOR

Continuous HAART consisting of lamivudine, lopinavir/ritonovir, and stavudine throughout the study; rabies vaccine at Weeks 16, 17, 22 and 92.

Drug: Lamivudine; Drug: Lopinavir/Ritonavir; Drug: Stavudine; Biological: Rabies de novo antigen

Interventions

Structured treatment interruption BEHAVIORAL

Interruptions in treatment will last 2, 4, and 8 weeks in between 16-week periods of ART

Also known as: STI

1

Lamivudine DRUG

300 mg tablet taken orally daily

1; 2

Lopinavir/Ritonavir DRUG

400 mg lopinavir/100 mg ritonavir tablet taken orally twice daily

1; 2

Stavudine DRUG

Dosage dependent on weight

1; 2

Rabies de novo antigen BIOLOGICAL

Vaccine injected intramuscularly

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Wistar Institute: lead

Study Sites (1)

University of the Witwatersrand

Johannesburg, South Africa

Location

Related Publications (9)

• Arnedo-Valero M, Garcia F, Gil C, Guila T, Fumero E, Castro P, Blanco JL, Miro 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. doi: 10.1086/432881. Epub 2005 Aug 4.

  PMID: 16107990 BACKGROUND

• 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. doi: 10.2174/1570162033485212.

  PMID: 15046257 BACKGROUND

• 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. doi: 10.1080/09540120701213849.

  PMID: 17453591 BACKGROUND

• 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. doi: 10.1097/00002030-200311070-00008.

  PMID: 14571185 BACKGROUND

• 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. doi: 10.1371/journal.pmed.0010064. Epub 2004 Dec 28.

  PMID: 15630469 BACKGROUND

• 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 observational study. J Int AIDS Soc. 2011 Jul 29;14:37. doi: 10.1186/1758-2652-14-37.

  PMID: 21801351 RESULT

• 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) vs. continuous therapy for HIV-1 infection. PLoS One. 2011;6(6):e21450. doi: 10.1371/journal.pone.0021450. Epub 2011 Jun 28.

  PMID: 21738668 RESULT

• 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. doi: 10.1214/10-AOAS326.

  PMID: 21274424 RESULT

• 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 study of a cohort of HIV-1-infected South African women. J Int AIDS Soc. 2010 Sep 7;13:33. doi: 10.1186/1758-2652-13-33.

  PMID: 20822522 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Treatment Interruption; Lamivudine; Lopinavir; Stavudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Treatment Adherence and Compliance; Attitude to Health; Delivery of Health Care; Health Care Quality, Access, and Evaluation; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Pyrimidinones; Thymidine

Study Officials

• Luis J. Montaner, DVM, MSc, DPhil

  The Wistar Institute

  PRINCIPAL INVESTIGATOR

• Ian M. Sanne, MBBCH, FCP(SA), DTM&H

  University of Witwatersrand, South Africa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, HIV-1 Immunopathogenesis Laboratory

Study Record Dates

• First Submitted: January 4, 2005
• First Posted: January 5, 2005
• Study Start: March 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: August 27, 2014

Record last verified: 2013-11

Locations

ZA (1)