HPTN 052

A Randomized Trial to Evaluate the Effectiveness of Antiretroviral Therapy Plus HIV Primary Care versus HIV Primary Care Alone to Prevent the Sexual Transmission of HIV-1 in Serodiscordant Couples

 

HPTN 052 Q & A - Preventing Sexual Transmission of HIV with Anti- HIV Drugs

Fact Sheet: Initiation of Antiretroviral Therapy (ART) Prevents Sexual Transmission of HIV in Serodiscordant Couples

Science Breakthrough of the Year

HPTN 052 Named Science Breakthrough of the Year, 2011

On 1 December, George Washington University in Washington, D.C., hosted “The Beginning of the End of AIDS,” a splashy World AIDS Day event that featured three U.S. presidents, business magnates, and rock stars. The catalyst that brought them together was something Anthony Fauci, the top U.S. government HIV/AIDS scientist, told the crowd even 1 year ago would have seemed “wishful thinking”: a clinical trial dubbed HPTN 052 and its “astounding” result. . . Read more

 

 

How did HPTN 052 change the landscape of HIV prevention research and what challenges remain for Treatment as Prevention?

Hear a StoryCorps conversation with HPTN 052 Protocol Chairs Mike Cohen and James Hakim.

 

See a complete list and links to all of the HPTN StoryCorps conversations.

What is HPTN 052?

HPTN 052 is a Phase III, two-arm, multi-site, randomized trial to determine the effectiveness of two treatment strategies in preventing the sexual transmission of HIV in HIV-serodiscordant couples.

Based on data collected in Africa and Thailand, there is a correlation between HIV viral load (blood levels) and HIV transmission.  Specifically, the higher the viral load in the blood, the more likely the chance for transmission.  Antiretroviral therapy (ART) reduces the viral load in the blood, as well as in genital secretions (for both men and women), and the drugs can be detected in semen and vaginal and cervical secretions.  All of this information strongly suggests that ART may make HIV-infected people less contagious.  HPTN 052 compares the HIV‑infection rates of two groups of HIV-serodiscordant couples.  The index case of the first group starts taking ART as soon as the couple is enrolled in the study, while the index case of the second group starts taking ART when he or she has two consecutive measurements of a CD4+ cell count within or below the range of 200-250 cells/mm3, or when he or she develops an AIDS-defining illness.  Both groups will receive HIV primary care and couples counseling sessions to teach them how to reduce their risk of transmission.

 

Protocol Status: Closed to Accrual

Study Summary

Study Purpose: The purpose of this study is to determine whether antiretroviral therapy (ART) can prevent the sexual transmission of HIV-1 in HIV-1 serodiscordant couples.

Study Design: The study is a Phase III, two-arm, randomized, controlled, multi-center trial.

Study Population: HIV serodiscordant couples in which the HIV-infected partner is ART naïve and has a CD4+ cell count of 350-550 cells/mm^3.

Study Size: Approximately 1750 couples total.

Study Duration: Approximately 78 months total. Accrual will require approximately 18 months total, and all couples will be followed until the last couple enrolled completes their 60-month follow-up visit.

Treatment Regimen: HIV-infected index cases will be assigned at random in a 1:1 ratio to one of two treatment arms: ARM 1: ART upon enrollment plus HIV primary care. ARM 2: HIV primary care without initiation of ART until the participant has two consecutive measurements of a CD4+ cell count within or below the range of 200-250 cells/mm^3, or develops an AIDS-defining illness. The ART drugs available for the study are Combivir [3TC/ZDV], ATV, EFV, NVP, TDF, 3TC, ddI-EC, d4T, Kaletra/Aluvia [LPV/r], and Truvada [FTC/TDF].

Primary Objectives: The primary objective of the study is to compare the rates of HIV infection among partners of HIV-infected participants in the two study arms below: (1) Antiretroviral therapy upon enrollment plus HIV primary care. (2) HIV primary care, without initiation of antiretroviral therapy until the participant has two consecutive measurements of a CD4+ cell count within or below the range of 200-250 cells/mm^3, or develops an AIDS-defining illness.

Secondary Objectives: To determine the long-term safety of two ART regimen strategies (ART immediately upon enrollment vs, ART when the participant has two consecutive measurements of a CD4+ cell count within or below the range of 200-250 cells/mm^3 or develops an AIDS-defining illness) for the treatment of HIV-1 infection. To characterize and compare the patterns and rates of antiretroviral drug resistance of two antiretroviral treatment strategies. To assess factors associated with and to compare adherence of two antiretroviral treatment strategies. To evaluate the usefulness of measures of virologic and immunologic efficacy, and measures to detect antiretroviral drug resistance. To determine, characterize, and compare the rates of AIDS-defining and HIV-related illnesses, sexually transmitted diseases, opportunistic infections, immune reconstitution syndromes, and other targeted medical conditions, with regard to outcomes and survival as observed in different geographic settings and by antiretroviral treatment strategies. To determine and characterize the rates of antiretroviral drug-associated toxicities observed in different geographic settings and by treatment strategies. To evaluate the effectiveness of couples HIV counseling and characterize the patterns of sexual behavior in couples in both arms of the study. To characterize and compare Quality of Life (QOL) indicators in different geographic settings and by antiretroviral treatment strategies. To determine, characterize and compare the effect of circumcision on HIV transmission in different geographic settings and by antiretroviral treatment strategies.


SDMC Protocol Specialist: Leslie Cottle get info

Protocol Co-Chair: Beatriz Grinsztejn get info

Protocol Co-Chair: Breno Riegel Santos get info

Protocol Co-Chair: David Celentano get info

Protocol Co-Chair: Irving F. Hoffman get info

Protocol Co-Chair: James Gita Hakim get info

Protocol Co-Chair: Johnstone Kumwenda get info

Protocol Co-Chair: Karin Alvarenga-Hyldgaard Nielsen get info

Protocol Co-Chair: Kenneth H. Mayer get info

Protocol Co-Chair: Mina Christine Hosseinipour get info

Protocol Co-Chair: Nagalingeshwaran Kumarasamy get info

Protocol Co-Chair: Suwat Chariyalertsak get info

Protocol Co-Chair: Taha Taha get info

Protocol Chair: Myron Scott Cohen get info

DAIDS Medical Officer: Vanessa Elharrar get info

CORE Protocol Specialist: Andrea Jennings get info

CORE Protocol Specialist: Marybeth McCauley get info

CORE Protocol Specialist: Theresa Gamble get info

Investigator of Record: Suwat Chariyalertsak   get info

Investigator of Record: Sheela V. Godbole get info

Investigator of Record: Beatriz Grinsztejn  get info

Investigator of Record: James Gita Hakim  get info

Investigator of Record: Mina Christine Hosseinipour  get info

Investigator of Record: Nagalingeshwaran Kumarasamy get info

Investigator of Record: Johnstone Kumwenda  get info

Investigator of Record: Joseph Makhema get info

Investigator of Record: Kenneth H. Mayer   get info

Investigator of Record: Lisa Mills get info

Investigator of Record: Ravindre Panchia get info

Investigator of Record: Breno Riegel Santos  get info

Investigator of Record: Ian Sanne get info

Investigator of Record: Jose Henrique da Silva Pilotto get info

Site Target
Enrollment
Cumulative
Enrollment
Implementation
Status
More
Info

Gaborone Prevention/Treatment Trials CRS

12701

Gaborone, Botswana

74 Couples

77 couples

Enrollment Closed

get more

Hospital Geral de Nova Iguaçu CRS (HGNI CRS)

30279

Nova Iguacu, Brazil

183 couples (HGNI and IPEC)

186 couples (HGNI and IPEC)

Enrollment Closed

get more

Hospital Nossa Senhora da Conceicao CRS

12201

Porto Alegre, Brazil

89 couples

90 couples

Enrollment Closed

get more

HSE-Hospital dos Servidores do Estado CRS

5072

Rio de Janeiro, Brazil

5 couples

5 couples

De-Registered

get more

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

12101

Rio de Janeiro, Brazil

183 couples (HGNI and IPEC)

186 couples (HGNI and IPEC)

Enrollment Closed

get more

YRG CARE Medical Ctr., VHS Chennai CRS

11701

Chennai, India

250 couples

250 couples

Enrollment Closed

get more

NARI Arogya Aadhar Clinic CRS

30295

Pune, India

173 couples across all NARI sites

175 couples across all NARI sites

Enrollment Closed

get more

NARI Clinic at Gadikhana Dr. Kotnis Municipal Dispensary CRS

11602

Pune, India

173 couples across all NARI sites

175 couples across all NARI sites

Enrollment Closed

get more

NARI Clinic at NIV CRS

11603

Pune, India

173 couples across all NARI sites

175 couples across all NARI sites

Enrollment Closed

get more

NARI Pune CRS

11601

Pune, India

173 couples across all NARI sites

175 couples across all NARI sites

Enrollment Closed

get more

NARI, Sassoon Gen. Hosp.

30296

Pune, India

173 couples across all NARI sites

175 couples across all NARI sites

Enrollment Closed

get more

NARI, Talera Municipal Hosp.

30297

Pune, India

173couples across all NARI sites

175 couples across all NARI sites

Enrollment Closed

get more

KEMRI/CDC CRS

31460

Kisumu, Kenya

59 couples

60 couples

Enrollment Closed

get more

College of Med. JHU CRS

30301

Blantyre, Malawi

229 couples

230 couples enrolled

Enrollment Closed

get more

Malawi CRS

12001

Lilongwe, Malawi

251 couples

251 couples

Enrollment Closed

get more

Soweto HPTN CRS

31610

Johannesburg, South Africa

49 Couples

50 couples

Enrollment Closed

get more

Witwatersrand Clinical Research Site

11101

Johannesburg, South Africa

44 couples

46 couples

Enrollment Closed

get more

Chiang Mai Univ. AIDS Prevention CRS

31458

Chiang Mai, Thailand

108 couples across all Chiang Mai sites

106 couples across all Chiang Mai sites

Enrollment Closed

get more

Chiang Mai Univ., Family Health Ctr.

30265

Chiang Mai, Thailand

108 couples across all Chiang Mai sites

106 couples across all Chiang Mai sites

Enrollment Closed

get more

Fenway Community Health Ctr. CRS

30272

Boston, United States

6 couples for the pilot

2 couples

De-Registered

get more

UZ-Parirenyatwa CRS

30313

Harare, Zimbabwe

239 couples

240 couples enrolled

Enrollment Closed

get more

HPTN 052 Publications

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim J, 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, et al. Prevention of HIV-1 infection with early antiretroviral therapy. NEJM. 2011, 365: 493-505 PMCID: 3200068

Eshleman SH, Hudelson SE, Redd AD, Wang L, Debes R, Chen YQ, Martens CA, Ricklefs SM, Selig EJ, Porcella SF, Munshaw S, Ray SC, Piwowar-Manning E, McCauley M, Hosseinipour MC, Kumwenda J, Hakim JG, Chariyalertsak S, de Bruyn G, Grinsztejn B, et al. Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network 052 trial. J Infect Dis. 2011, 204: 1918-26 PMCID: 3209811

Chen YQ, Masse B, Wang L, Ou SS, Li X, Donnell D, McCauley M, Gamble T, Ribauldo HJ, Cohen MS, Fleming TR. Statistical considerations for the HPTN 052 Study to evaluate the effectiveness of early versus delayed antiretroviral strategies to prevent the sexual transmission of HIV-1 in serodiscordant couples. Contemp Clin Trials. 2012, 33: 1280-6 PMCID:3468650

Cohen MS, McCauley M, Gamble TR. HIV treatment as prevention and HPTN 052. Curr Opin HIV AIDS. 2012, 7: 99-105 PMCID: 3486734

Cohen, MS, McCauley, M, Sugarman, J. Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey. Clin Trials. 2012, 9: 340-7 PMCID: 3486723

Fogel JM, Wang L, Parsons TL, Ou SS, Piwowar-Manning E, Chen Y, Mudhune VO, Hosseinipour MC, Kumwenda J, Hakim JG, Chariyalertsak S, Panchia R, Kumarasamy N, Grinsztejn B, Makhema J, Pilotto J, Santos BR, Mayer KH, McCauley M, Gamble T, et. Al. Undisclosed antiretroviral drug use in a multi-national clinical trial (HPTN 052). J Infect Dis. 2013, 208: 1624-8 PMCID: 3805242

Ping LH, Jabara CB, Rodrigo AG, Hudelson SE, Piwowar-Manning E, Wang L, Eshleman SH, Cohen MS, Swanstrom R. HIV-1 transmission during early antiretroviral therapy: evaluation of two HIV-1 transmission events in the HPTN 052 prevention study. PloS One. 2013, 8: e71557. PMCID: 3782474

Walensky RP, Ross EL, Kumarasamy N, Wood R, Noubary F, Paltiel AD, Nakamura YM, Godbole SV, Panchia R, Sanne I, Weinstein MC, Losina E, Mayer KH, Chen YQ, Wang L, McCauley M, Gamble T, Seage GR 3rd, Cohen MS, Freedberg KA.. Cost-effectiveness of HIV treatment as prevention in serodiscordant couples. NEJM. 2013, 369: 1715-25 PMCID: 3913536

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, et.al. 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, 14: 281-90 PMCID: 4144040