Prevention of HIV-1 Infection with Early Antiretroviral Therapy
In this large, international study of HIV-1–serodiscordant couples, the receipt of antiretroviral therapy by the infected partner decreased transmission to the uninfected partner as well as rates of clinical events in the HIV-1–infected partner. Combination antiretroviral therapy decreases the repli...
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| Published in | The New England journal of medicine Vol. 365; no. 6; pp. 493 - 505 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Waltham, MA
Massachusetts Medical Society
11.08.2011
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0028-4793 1533-4406 1533-4406 |
| DOI | 10.1056/NEJMoa1105243 |
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| Abstract | In this large, international study of HIV-1–serodiscordant couples, the receipt of antiretroviral therapy by the infected partner decreased transmission to the uninfected partner as well as rates of clinical events in the HIV-1–infected partner.
Combination antiretroviral therapy decreases the replication of human immunodeficiency virus type 1 (HIV-1) and improves the survival of infected persons.
1
,
2
Such therapy has been shown to reduce the amount of HIV-1 in genital secretions.
3
–
5
Because the sexual transmission of HIV-1 from infected persons to their partners is strongly correlated with concentrations of HIV-1 in blood
6
and in the genital tract,
7
it has been hypothesized that antiretroviral therapy could reduce sexual transmission of the virus. Several observational studies have reported decreased acquisition of HIV-1 by sexual partners of patients receiving antiretroviral therapy.
8
–
11
These results have been extrapolated to . . . |
|---|---|
| AbstractList | Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.
In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.
As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01).
The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.). Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.BACKGROUNDAntiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.METHODSIn nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01).RESULTSAs of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01).The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).CONCLUSIONSThe early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.). In this large, international study of HIV-1–serodiscordant couples, the receipt of antiretroviral therapy by the infected partner decreased transmission to the uninfected partner as well as rates of clinical events in the HIV-1–infected partner. Combination antiretroviral therapy decreases the replication of human immunodeficiency virus type 1 (HIV-1) and improves the survival of infected persons. 1 , 2 Such therapy has been shown to reduce the amount of HIV-1 in genital secretions. 3 – 5 Because the sexual transmission of HIV-1 from infected persons to their partners is strongly correlated with concentrations of HIV-1 in blood 6 and in the genital tract, 7 it has been hypothesized that antiretroviral therapy could reduce sexual transmission of the virus. Several observational studies have reported decreased acquisition of HIV-1 by sexual partners of patients receiving antiretroviral therapy. 8 – 11 These results have been extrapolated to . . . BackgroundAntiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.MethodsIn nine countries, we enrolled 1763 couples in which one partner was HIV-1–positive and the other was HIV-1–negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1–infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1–related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1–negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.ResultsAs of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01).ConclusionsThe early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.) |
| Author | Gamble, Theresa Eron, Joseph Hakim, James G Mayer, Kenneth H Hoffman, Irving F Eshleman, Susan H Kumarasamy, Nagalingeswaran Kumwenda, Johnstone Hosseinipour, Mina C Godbole, Sheela V Celentano, David Burns, David Makhema, Joseph Mills, Lisa A Ribaudo, Heather Fleming, Thomas R McCauley, Marybeth Chariyalertsak, Suwat Chen, Ying Q Mehendale, Sanjay Havlir, Diane Swindells, Susan Piwowar-Manning, Estelle Sanne, Ian Taha, Taha E Pilotto, Jose H.S de Bruyn, Guy Elharrar, Vanessa Nielsen-Saines, Karin Cohen, Myron S Santos, Breno R Gallant, Joel Grinsztejn, Beatriz Wang, Lei Essex, Max |
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| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24404657$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21767103$$D View this record in MEDLINE/PubMed |
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| Contributor | Sahay, Seema da Silva, André L Freitas, Ricardo H Thakar, Madhuri Ramalho, Aline Simon, Mariana R Kliemann, Dimas A Perez, Consuelo F Castro, Andréa C Kanitkar, Swapna Friedman, Ruth Khalili Paiva, Margarete do Nascimento, Maria Isabel Flores, Rui Gelman, Marcy Joglekar, Neelam Silveira, Mara L Rocha, Maria R Krishnan, Sumitra de Chã, Tatiana Muniz Mane, Arati Curra, Leda Ramos, Deise T Bustorff, Flavio Pimenta, Cristina Tuler, Lidiane Sharma, Jabin Safren, Steven Filgueiras, Sandra Beri, Archana Gangakhedkar, Raman Joao, Esau C Katti, Usha Sena, Lucia Brahme, Radhika Rodrigues, Ana Claudia Waite, Daniel de Oliveira, Marilia Santini Cardoso, Sandra Wagner Kale, Varsha Turella, Maria L Grudzinski, Melina dos Santos, Roberta F Campello, Cláudio M Fernandes, Carmen L Raxach, Juan C Ribeiro, Valeria Ghate, Manisha Brum, Tania Thamburaj, Easter Maldonado, Ana Hoagland, Brenda Selvamuthu, Poongulalli Singal, Robbie Georg, Ingeborg Paranjape, Ramesh Srikrishnan, Aylur Kailasom Dhayarkar, Sampada da Silva, Cintia Lopes Deshmukh, Rajeshwari Kulkarni, Sa |
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| Copyright | Copyright © 2011 Massachusetts Medical Society. All rights reserved. 2015 INIST-CNRS Copyright © 2011 Massachusetts Medical Society. 2011 |
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| Snippet | In this large, international study of HIV-1–serodiscordant couples, the receipt of antiretroviral therapy by the infected partner decreased transmission to the... Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. In... BackgroundAntiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant... Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant... |
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| SubjectTerms | Adolescent Adult Allergies Anti-Retroviral Agents - adverse effects Anti-Retroviral Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral drugs Antiretroviral therapy Antiviral agents Biological and medical sciences CD4 antigen Counseling Couples Disease prevention Disease Progression Disease transmission Disease Transmission, Infectious - prevention & control Drug therapy Drug Therapy, Combination Enrollments Fees & charges Female General aspects Grants HIV HIV Infections - drug therapy HIV Infections - prevention & control HIV Infections - transmission HIV Seropositivity HIV-1 Human immunodeficiency virus Human viral diseases Humans Infections Infectious diseases Kaplan-Meier Estimate Laboratories Male Medical sciences Pharmacology. Drug treatments Population Proportional Hazards Models Public health Sexual Partners Sexual transmission Spouses Treatment Outcome Tuberculosis Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Young Adult |
| Title | Prevention of HIV-1 Infection with Early Antiretroviral Therapy |
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