Preventing Sexual Transmission of HIV With Anti-HIV Drugs

NCT00074581 | Completed Phase 3 Results

• 2 other identifiers: HPTN 05210068
• Study Type: interventional
• Target: 3,526
• Locations: 9 countries
• Sites: 17

Brief Summary

This study will determine whether anti-HIV drugs can prevent the sexual transmission of HIV among couples in which one partner is HIV infected and the other is not.

Conditions

HIV Infections

Keywords

HIV Infections; HIV Seronegativity

Outcome Measures

Primary Outcomes (2)

• Linked Partner HIV Infection Rates in Early-ART and Delayed-ART Arms

  incident HIV infections occurring in the partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases are assessed, by arm. Only acquisition from the index partner were included in the primary analysis, therefore, each endpoint was required to be confirmed (by genotyping) such that the viral envelop sequence in the index case matched that of the partner.

  Throughout study

• All Partner HIV Infection Rates in Early-ART and Delayed-ART Arms

  All Incident HIV infections occurring in the partners (HIV-negative at enrollment) of randomized HIV-infected index (HIV-positive at enrollment) cases are assessed, by arm.

  Throughout study

Study Arms (2)

1

EXPERIMENTAL

Participants will begin ART in addition to receiving HIV primary care

Drug: Atazanavir; Drug: Didanosine; Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Lamivudine; Drug: Lopinavir/Ritonavir; Drug: Nevirapine; Drug: Stavudine; Drug: Tenofovir disoproxil fumarate; Drug: Zidovudine/Lamivudine

2

EXPERIMENTAL

Participants will receive HIV primary care. When the CD4 count in these participants reaches 200 to 250 cells/mm3, drops below 200 cells/mm3, or develops an AIDS-defining illness, they will initiate ART. Note: Per LoA#5, on the Data and Safety and Monitoring Board (DSMB) recommendation, as of May 10, 2011, all HIV-infected participants in Arm 2 who have not already initiated ART will be offered ART as soon as possible.

Drug: Atazanavir; Drug: Didanosine; Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Lamivudine; Drug: Lopinavir/Ritonavir; Drug: Nevirapine; Drug: Stavudine; Drug: Tenofovir disoproxil fumarate; Drug: Zidovudine/Lamivudine

Interventions

Atazanavir DRUG

300 mg taken orally once daily

Also known as: Reyataz

1; 2

Didanosine DRUG

400 mg taken orally once daily

Also known as: Videx

1; 2

Efavirenz DRUG

600 mg taken orally once daily

Also known as: Sustiva

1; 2

Emtricitabine/Tenofovir disoproxil fumarate DRUG

200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally once daily

Also known as: Truvada

1; 2

Lamivudine DRUG

300 mg taken orally once daily

Also known as: Epivir, 3TC

1; 2

Lopinavir/Ritonavir DRUG

200 mg lopinavir/ 50 mg ritonavir tablet taken orally once daily

Also known as: Kaletra

1; 2

Nevirapine DRUG

200 mg taken orally once daily for 14 days followed by 200 mg taken orally twice daily

Also known as: Viramune, NVP

1; 2

Stavudine DRUG

Dosage depends on weight

Also known as: Zerit, d4T

1; 2

Tenofovir disoproxil fumarate DRUG

300 mg taken orally once daily

Also known as: Viread, TDF

1; 2

Zidovudine/Lamivudine DRUG

150 mg lamivudine/ 300 mg zidovudine tablet taken orally twice daily

Also known as: Combivir

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Positive HIV test within 60 days of study entry
• CD4 count between 350 and 550 cells/mm3 within 30 days of study entry
• If pregnant or breastfeeding, willing to be randomized to either arm of the study
• Negative HIV test within 14 days of study entry
• Plans to maintain sexual relationship with partner
• Reports having sex (vaginal or anal) with partner at least three times in the last 3 months
• Willing to disclose HIV test results to partner
• Plans to stay in the area and does not have a job or other obligations that may require long absences during the duration of the study

You may not qualify if:

• Current or previous use of any ART. Participants who previously took a short-term course of ART for prevention of mother-to-child transmission of HIV are not excluded.
• Documented or suspected acute hepatitis within 30 days of study entry, if the infected partner's starting regimen in the study contains nevirapine or atazanavir
• Current or previous AIDS-defining illness or opportunistic infection
• Documented or suspected acute hepatitis within 30 days prior to study entry
• Acute therapy of serious medical illnesses within 14 days prior to study entry
• Radiation therapy or systemic chemotherapy within 45 days prior to study entry
• Immunomodulatory or investigational therapy within 30 days prior to study entry
• Active drug or alcohol dependence that, in the opinion of the investigator, would interfere with the study
• Vomiting or inability to swallow medications
• Require certain medications
• Allergy or sensitivity to any of the study drugs
• History of injection drug use within 5 years of study entry
• Previous and/or current participation in an HIV vaccine study
• Currently detained in jail or for treatment of a psychiatric or physical illness
• Any condition that, in the opinion of the study staff, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Prevention Trials Network: collaborator

Study Sites (17)

Fenway Community Health Ctr. CRS

Boston, Massachusetts, 02115, United States

Location

Gaborone CRS

Gaborone, Botswana

Location

Hospital Geral de Nova Iguaçu CRS (HGNI CRS)

Nova Iguaçu, Rio de Janeiro, 26030-380, Brazil

Location

Hospital Nossa Senhora da Conceicao CRS

Port Alegre, Rio Grande do Sul, 91350 200, Brazil

Location

HSE-Hospital dos Servidores do Estado CRS

Rio de Janeiro, 20221-903, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-360, Brazil

Location

NARI Clinic at Gadikhana Dr. Kotnis Municipal Dispensary CRS

Pune, Maharashtra, 411002, India

Location

NARI Clinic at NIV CRS

Pune, Maharashtra, 411011, India

Location

NARI Pune CRS

Pune, Maharashtra, 411026, India

Location

Chennai Antiviral Research and Treatment (CART) CRS

Chennai, Tamil Nadu, 600113, India

Location

Kisumu Crs

Kisumu, Nyanza, 40100, Kenya

Location

Blantyre CRS

Blantyre, Malawi

Location

Malawi CRS

Lilongwe, Malawi

Location

Soweto HPTN CRS

Johannesburg, Gauteng, 2001, South Africa

Location

Wits Helen Joseph Hospital CRS (Wits HJH CRS)

Johannesburg, Gauteng, 2092, South Africa

Location

CMU HIV Prevention CRS

Chiang Mai, 50202, Thailand

Location

Parirenyatwa CRS

Harare, Zimbabwe

Location

Related Publications (8)

• Chan DJ. Fatal attraction: sex, sexually transmitted infections and HIV-1. Int J STD AIDS. 2006 Oct;17(10):643-51. doi: 10.1258/095646206780071018.

  PMID: 17059632 BACKGROUND

• Chan DJ. Factors affecting sexual transmission of HIV-1: current evidence and implications for prevention. Curr HIV Res. 2005 Jul;3(3):223-41. doi: 10.2174/1570162054368075.

  PMID: 16022655 BACKGROUND

• Davis CW, Doms RW. HIV transmission: closing all the doors. J Exp Med. 2004 Apr 19;199(8):1037-40. doi: 10.1084/jem.20040426. Epub 2004 Apr 12. No abstract available.

  PMID: 15078894 BACKGROUND

• Gupta K, Klasse PJ. How do viral and host factors modulate the sexual transmission of HIV? Can transmission be blocked? PLoS Med. 2006 Feb;3(2):e79. doi: 10.1371/journal.pmed.0030079. Epub 2006 Feb 28.

  PMID: 16492075 BACKGROUND

• Odero I, Ondeng'e K, Mudhune V, Okola P, Oruko J, Otieno G, Akelo V, Gust DA. Participant satisfaction with clinical trial experience and post-trial transitioning to HIV care in Kenya. Int J STD AIDS. 2019 Jan;30(1):12-19. doi: 10.1177/0956462418791946. Epub 2018 Aug 29.

  PMID: 30157702 DERIVED

• Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR; HPTN 052 Study Team. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med. 2016 Sep 1;375(9):830-9. doi: 10.1056/NEJMoa1600693. Epub 2016 Jul 18.

  PMID: 27424812 DERIVED

• Grinsztejn B, Hosseinipour MC, Ribaudo HJ, Swindells S, Eron J, Chen YQ, Wang L, Ou SS, Anderson M, McCauley M, Gamble T, Kumarasamy N, Hakim JG, Kumwenda J, Pilotto JH, Godbole SV, Chariyalertsak S, de Melo MG, Mayer KH, Eshleman SH, Piwowar-Manning E, Makhema J, Mills LA, Panchia R, Sanne I, Gallant J, Hoffman I, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Havlir D, Cohen MS; HPTN 052-ACTG Study Team. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect Dis. 2014 Apr;14(4):281-90. doi: 10.1016/S1473-3099(13)70692-3. Epub 2014 Mar 4.

  PMID: 24602844 DERIVED

• Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18.

  PMID: 21767103 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Atazanavir Sulfate; Didanosine; efavirenz; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Lamivudine; Lopinavir; lopinavir-ritonavir drug combination; Nevirapine; Stavudine; Tenofovir; lamivudine, zidovudine drug combination

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)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Drug Combinations; Pharmaceutical Preparations; Zalcitabine; Pyrimidinones; Thymidine

Results Point of Contact

• Title: Dr. Deborah Donnell
• Organization: Fred Hutchinson Cancer Research Center

deborah@scharp.org

2066675661

Study Officials

• Myron S. Cohen, MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2003
• First Posted: December 17, 2003
• Study Start: February 1, 2005
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: November 5, 2021
• Results First Posted: October 31, 2016

Record last verified: 2016-11

Locations

BR (4); US (1); MA (2); KE (1); BO (1); ZA (2); ZI (1); IN (4); TH (1)