Acyclovir to Treat Patients Co-infected With HIV and Herpes Viruses in Uganda

NCT00405821 | Completed Phase 2 Results DMC

• 2 other identifiers: 99990703207-I-N032
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine whether acyclovir, a medicine used to treat herpes simplex virus 2 (HSV-2), can slow down the progression (worsening) of HIV disease in people with both HIV and HSV-2 infections. HSV-2 increases the amount of HIV virus in the blood of infected people and may make HIV progress faster. The study will evaluate: "Whether people who take acyclovir can avoid antiretroviral treatment until later in their lives "Whether people who take acyclovir get fewer genital ulcers "How well people are able to take acyclovir and any side effects they experience from it "Differences in the amount of HIV virus in the blood of patients who are and are not taking acyclovir, and how HIV/AIDS is different in these patients. People 18 years of age and older living in the Rakai district of Uganda who are infected with both HIV (early stage disease) and HSV-2 may be eligible for this study. Participants are randomly assigned to take the study drug, acyclovir, or a placebo (look-alike pill with no active ingredient) daily for 2 years. During this time, they visit the clinic once a month for a routine physical examination. Patients who develop genital ulcers or complications of HIV are treated for the problem, and patients whose HIV disease progresses, requiring them to begin antiretroviral therapy, are treated accordingly.

Conditions

HIV Infections; Herpes Genitalis

Keywords

AIDS; HIV Disease Progression; Quality of Life; HIV Viral Load; Genital Ulcers; HIV; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• Progression to AIDS (CD4+ Less Than 250 Cells/Microliter or World Health Org Stage IV dx, Excluding Esophageal Candidiasis)

  Evaluate the effect of acyclovir prophylaxis vs placebo among HIV-1/HSV-2 co-infected individuals on the progression to AIDS (CD4+ less than 250 cells/microliter or World Health Org stage IV disease, excluding esophageal candidiasis)

  2 years

Secondary Outcomes (5)

• Difference in Number of Episodes of Genital Ulcer Disease Between Arms

  2 years

• HIV-1 Viral Load Difference Between Arms

  baseline, 6 months, 12 months, 18 months, 24 months

• Toxicity of Acyclovir

  2 years

• Adherence to Acyclovir

  2 years

• Virologic and Immunologic Responses to ART in Those Who Progress to CD+4 Less Than 250cells/mL

  6 months and 12 moths post ART initiation

Study Arms (2)

Acyclovir 400mg tablet twice daily

ACTIVE COMPARATOR

Drug: Acyclovir

Placebo tablet twice daily

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Acyclovir DRUG

400mg twice daily for 24 months

Acyclovir 400mg tablet twice daily

Placebo DRUG

Placebo tablet twice daily for 24 months

Placebo tablet twice daily

Eligibility Criteria

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

You may qualify if:

• Documentation of HIV-1 infection, by either two positive ELISAs or two discrepant ELISAs with a confirmatory positive Western Blot
• Documentation of prior HSV-2 infection by Focus Kalon ELISA
• Absolute CD4+ T-cell count of greater than or equal to 300 and less than or equal to 400 cells/microliter within 30 days prior to randomization
• All participants must be receiving Cotrimoxazole prophylaxis as part of standard care unless contraindicated
• Age at least 18 years and above
• Laboratory values (within 30 days prior to randomization)
• Aspartate transaminase (AST) no more than five times the upper limit of normal (ULN)
• Total bilirubin no more than 2 times ULN
• Creatinine no more than 2.0 mg/dL
• Platelet count at least 50 000/microliter
• Hemoglobin at least 8g/dL
• Written informed consent

You may not qualify if:

• Concurrent malignancy or any other disease state requiring cytotoxic chemotherapy
• Symptomatic for significant HIV-related illnesses (WHO stage III or IV), such as opportunistic infections and malignancies other than mucocutaneous Kaposi's sarcoma. A history of AIDS defining opportunistic infections other than mucocutaneous Kaposi's sarcoma or candida or treated tuberculosis
• Active HSV-2 disease as suggested by painful genital ulcer disease at time of screening or enrollment
• Current use of antiretroviral medications or Preventing Mother-to-Child Transmission (PMTCT) use of antiretrovirals within the previous 6 months
• Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine medical history, physical examination, or screening laboratory studies.
• Psychiatric illness that, in the opinion of the PI, might interfere with the study compliance.
• Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or patient safety.
• CD4+ count less than 300 or more than 400 cells/microliter.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• University of Washington: collaborator
• Johns Hopkins University: collaborator
• Translational Genomics Research Institute: collaborator

Study Sites (1)

Rakai Health Sciences Program, Uganda Virus Research Institute

Kalisizo, Rakai District, Uganda

Location

Related Publications (5)

• Moriuchi M, Moriuchi H, Williams R, Straus SE. Herpes simplex virus infection induces replication of human immunodeficiency virus type 1. Virology. 2000 Dec 20;278(2):534-40. doi: 10.1006/viro.2000.0667.

  PMID: 11118375 BACKGROUND

• Serwadda D, Gray RH, Sewankambo NK, Wabwire-Mangen F, Chen MZ, Quinn TC, Lutalo T, Kiwanuka N, Kigozi G, Nalugoda F, Meehan MP, Ashley Morrow R, Wawer MJ. Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda. J Infect Dis. 2003 Nov 15;188(10):1492-7. doi: 10.1086/379333. Epub 2003 Oct 28.

  PMID: 14624374 BACKGROUND

• Stein DS, Graham NM, Park LP, Hoover DR, Phair JP, Detels R, Ho M, Saah AJ. The effect of the interaction of acyclovir with zidovudine on progression to AIDS and survival. Analysis of data in the Multicenter AIDS Cohort Study. Ann Intern Med. 1994 Jul 15;121(2):100-8. doi: 10.7326/0003-4819-121-2-199407150-00004.

  PMID: 8017721 BACKGROUND

• Redd AD, Newell K, Patel EU, Nalugoda F, Ssebbowa P, Kalibbala S, Frank MA, Tobian AA, Gray RH, Quinn TC, Serwadda D, Reynolds SJ. Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women. Sex Transm Infect. 2015 Nov;91(7):485-8. doi: 10.1136/sextrans-2014-051867. Epub 2015 Apr 22.

  PMID: 25904747 DERIVED

• Reynolds SJ, Makumbi F, Newell K, Kiwanuka N, Ssebbowa P, Mondo G, Boaz I, Wawer MJ, Gray RH, Serwadda D, Quinn TC. Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial. Lancet Infect Dis. 2012 Jun;12(6):441-8. doi: 10.1016/S1473-3099(12)70037-3. Epub 2012 Mar 19.

  PMID: 22433279 DERIVED

MeSH Terms

Conditions

HIV Infections; Herpes Genitalis; Acquired Immunodeficiency Syndrome

Interventions

Acyclovir

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; Herpes Simplex; Herpesviridae Infections; DNA Virus Infections; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Male; Male Urogenital Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Steven Reynolds
• Organization: NIAID

sjreynolds@niaid.nih.gov

256-772-220-087

Study Officials

• Steven J Reynolds, MD

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Director NIH-Uganda ICER

Study Record Dates

• First Submitted: November 29, 2006
• First Posted: November 30, 2006
• Study Start: November 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: November 1, 2010
• Last Updated: September 28, 2012
• Results First Posted: September 28, 2012

Record last verified: 2012-08

Locations

UG (1)