6th IAS Conference On HIV Pathogenesis, Treatment and Prevention

Treatment Is Prevention: The Proof Is Here MOAX01

Type:
Oral Abstract Session Back
Venue: SR 1
Time: 16:30 - 18:00, 18.07.2011
Code: MOAX01
Chairs: Bertrand Audoin, Switzerland
James Hakim, Zimbabwe



Presentations in this session:

16:30
MOAX0101
Introduction



16:35
MOAX0102
Abstract
Powerpoint
Antiretroviral treatment to prevent the sexual transmission of HIV-1: results from the HPTN 052 multinational randomized controlled trial
Presented by Myron Cohen, United States
M. Cohen1, Y. Chen2, M. McCauley3, T. Gamble4, R. Bollinger5, Y. Bryson6, D. Burns7, D. Celentano8, S. Chariyalertsak9, F. Conradie10, L. Cottle2, G. de Bruyn10, V. Elharrar7, S. Eshelman5, M. Essex11, E.C.J. Filho12, S. Godbole13, B. Grinsztejn14, J.G. Hakim15, I.F. Hoffman1, M. Hosseinipour1, N. Kumarasamy16, J. Kumwenda17, J. Makhema18, A. Martinez7, K.H. Mayer19, S. Mehendale13, L.A. Mills20, K.A.-H. Nielsen6, J.H.d.S. Pilotto21, E. Piwowar-Manning5, I. Sanne10, B.R. Santos22, T. Taha5, L. Wang2, S. Safren23, T. Fleming2, HPTN052 Protocol Team
1University of North Carolina at Chapel Hill, Chapel Hill, United States, 2University of Washington, Seattle, United States, 3Family Health International, Arlington, United States, 4Family Health International, Durham, United States, 5Johns Hopkins University, Baltimore, United States, 6University of California at Los Angeles, Los Angeles, United States, 7National Institute of Allergy and Infectious Diseases, Bethesda, United States, 8Johns Hopkins Bloomberg School of Public Health, Baltimore, United States, 9Ciang Mai University, Chiang Mai, Thailand, 10University of the Witwatersrand, Johannesburg, South Africa, 11Harvard School of Public Health, Boston, United States, 12Hospital dos Servidores do Estado, Rio de Janeiro, Brazil, 13National AIDS Research Institute, Pune, India, 14Instituto de Pesquisa Clínica Evandro Chagas, Rio de Janeiro, Brazil, 15University of Zimbabwe, Harare, Zimbabwe, 16Y. R. Gaitonade Center for AIDS Research and Education, Chennai, India, 17College of Medicine, Blantyre, Malawi, 18Botswana Harvard School of Public Health AIDS Initiative Partnership, Gaborone, Botswana, 19Fenway Institute, Boston, United States, 20KEMRI-CDC Research and Public Health Collaboration, Atlanta, United States, 21Hospital Geral de Nova Iguaçu, Rio de Janeiro, Brazil, 22Hospital Nossa Senhora da Conceiçao/GHC, Porto Alegre, Brazil, 23Harvard University, Boston, United States

16:49
MOAX0103
Abstract
Powerpoint
Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network (HPTN) 052 trial
Presented by Susan Eshleman, United States
J. Hughes1, S. Hudelson2, A. Redd3, L. Wang4, R. Debes1, Y. Chen4, S. Porcella5, E. Piwowar-Manning2, M. McCauley6, M. Hosseinipour7,8, J. Kumwenda9, J. Hakim10, S. Chariyalertsak11, G. de Bruyn12, B. Grinsztejn13, N. Kumarasamy14, J. Makhema15, K. Mayer16, J. Pilotto17, B. Santos18, T. Quinn2,3, M. Cohen8, S. Eshleman2, HPTN 052
1University of Washington, Seattle, United States, 2Johns Hopkins University School of Medicine, Baltimore, United States, 3National Institutes of Health, Baltimore, United States, 4Fred Hutchinson Cancer Research Center, Seattle, United States, 5National Institutes of Health, Hamilton, United States, 6Family Health International, Arlington, United States, 7Kamuzu Central Hospital, Lilongwe, Malawi, 8University of North Carolina at Chapel Hill, Chapel Hill, United States, 9College of Medicine, Blantyre, Malawi, 10University of Zimbabwe, Harare, Zimbabwe, 11Chiang Mai University, Chaing Mai, Thailand, 12University of the Witwatersrand, Johannesburg, South Africa, 13Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil, 14YRG Care Medical Center, Chennai, India, 15Botswana-Harvard School of Public Health AIDS Initiative Partnership, Gabarone, Botswana, 16Fenway Health, Boston, United States, 17Hospital Geral de Nova Iguaçu and Laboratorio de AIDS e Imunologia Molecular - IOC/Fiocruz, Rio de Janeiro, Brazil, 18Hospital Nossa Senhora da Conceicao, Porto Alegre, Brazil

16:59
MOAX0104
Abstract
Powerpoint
Immunologic and virologic disease progression and responses to ART across geographic regions: outcomes from HPTN 052 study
Presented by Mina Hosseinipour, Malawi
M.C. Hosseinipour1,2, L. Wang3, M.S. Cohen2, S. Chariyalertsak4, Y.Q. Chen3, V. Elharrar5, S. Eshleman6, J. Gallant6, T. Gamble7, S. Godbole8, S. Govinder9, B. Grinsztejn10, J.G. Hakim11, D. Havlir12, P. Ive9, K. Klingman5, N. Kumarasamy13, J. Kumwenda14, J. Makhema15, K. Mayer16, M. McCauley17, L. Mills18, J. Pilotto19, E. Piwowar-Manning6, H. Ribaudo20, B.R. Santos21, S. Swindells22, J.J. Eron2, and the HPTN 052 study team
1UNC Project, Lilongwe, Malawi, 2University of North Carolina, Chapel Hill, United States, 3Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, United States, 4Chiang Mai University, Chiang Mai, Thailand, 5National Institute of Allergy and Infectious Diseases, Bethesda, United States, 6John Hopkins University, Baltimore, United States, 7FHI, Durham, United States, 8National AIDS Institute, Pune, India, 9University of Witwatersrand, Johannesburg, South Africa, 10Instituto de Pesquisa Clínica Evandro Chagas, Rio de Janeiro, Brazil, 11University of Zimbabwe, Harare, Zimbabwe, 12University of California, San Francisco, United States, 13YRG Care Medical Center, Chennai, India, 14College of Medicine, Blantyre, Malawi, 15Botswana Harvard School of Public Health AIDS Initiative Partnership, Gaborone, Botswana, 16Fenway Health, Boston, United States, 17FHI, Arlington, United States, 18KEMRI-CDC Research and Public Health Collaboration, Atlanta, United States, 19Hospital Geral de Nova Iguaçu, Rio de Janeiro, Brazil, 20Harvard University, Boston, United States, 21Hospital Nossa Senhora da Conceiçao/GHC, Porto Alegre, Brazil, 22University of Nebraska Medical Center, Omaha, United States

17:09
MOAX0105
Abstract
Powerpoint
Effects of early versus delayed initiation of antiretroviral therapy (ART) on HIV clinical outcomes: results from the HPTN 052 randomized clinical trial
Presented by Beatriz Grinsztejn, Brazil
B. Grinsztejn1, H. Ribaudo2, M.S. Cohen3, S. Swindells4, S. Badel-Faesen5, D. Burns6, S. Chariyalertsak7, Y.Q. Chen8, G. de Bruyn9, J.J. Eron10, S. Eshleman11, T. Fleming12, J. Gallant11, T. Gamble13, S.V. Godbole14, J.G. Hakim15, M.C. Hosseinipour10,16, K. Klingman17, N. Kumarasamy18, J. Kumwenda19, J. Makhema20, K.H. Mayer21, M. McCauley22, L.A. Mills23, J.H. Pilotto24,25, E. Piwowar-Manning26, B.R. Santos27, L. Wang8, D. Havlir28, HPTN 052 Protocol Team
1Oswaldo Cruz Foundation, Instituto de Pesquisa Clínica Evandro Chagas, Rio de Janeiro, Brazil, 2Harvard University, Boston, United States, 3University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, United States, 4University of Nebraska Medical Center, Omaha, United States, 5WITS Health Consortium- University of Witwatersrand, Department of Medicine, Johannesburg, South Africa, 6National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS, Prevention Sciences Branch, Bethesda, United States, 7University of Chiang Mai, Chiang Mai, Thailand, 8Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seatle, United States, 9Chris Hani Baragwanath Hospital, PHRU, Soweto, South Africa, 10University of North Carolina at Chapel Hill, Chapel Hill, United States, 11Johns Hopkins University School of Medicine, Baltimore, United States, 12University of Washington, Seatle, United States, 13FHI, Durham, United States, 14National AIDS Research Institute, Pune, India, 15University of Zimbabwe, Department of Medicine, Harare, Zimbabwe, 16UNC Project Lilongwe, Lilongwe, Malawi, 17National Insitute of Allergy and Infectious Diseases, Bethesda, United States, 18YRG Care Medical Center, Chennai, India, 19College of Medicine, Blantyre, Malawi, 20Botswana Harvard School of Public Health AIDS Initiative Partnership, Gaborone, Botswana, 21Fenway Institute, Boston, United States, 22FHI, Arlington, United States, 23KEMRI/CDC Research and Public Health Collaboration, Atlanta, United States, 24Hospital Geral de Nova Iguaçu, Nova Iguaçu, Brazil, 25IOC/FIOCRUZ, Laboratorio de AIDS e Imunologia Molecular, Rio d

17:19

Powerpoint
Summary
Presented by Myron Cohen, United States



17:23
Questions and answers



17:30
WELBC01
Abstract
Powerpoint
Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study
Presented by Michael C Thigpen, United States
M.C. Thigpen1, P.M. Kebaabetswe2, D.K. Smith1, T.M. Segolodi2, F.A. Soud1, K. Chillag1, L.I. Chirwa2, M. Kasonde2, R. Mutanhaurwa2, F.L. Henderson1, S. Pathak1, R. Gvetadze1, C.E. Rose1, L.A. Paxton1, for the TDF2 Study Group
1Center for Disease Control and Prevention (CDC), Division of HIV/AIDS Prevention, Atlanta, United States, 2BOTUSA, HIV Prevention Research Unit, Gaborone, Botswana

17:40
MOAX0106
Powerpoint
Antiretroviral Pre-Exposure Prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP Study
Presented by Jared Baeten, United States



17:45
Summary and conclusion



17:50
Questions and answers





Powerpoints presentations
Antiretroviral treatment to prevent the sexual transmission of HIV-1: results from the HPTN 052 multinational randomized controlled trial - Myron Cohen

Analysis of genetic linkage of HIV from couples enrolled in the HIV Prevention Trials Network (HPTN) 052 trial - Susan Eshleman

Immunologic and virologic disease progression and responses to ART across geographic regions: outcomes from HPTN 052 study - Mina Hosseinipour

Effects of early versus delayed initiation of antiretroviral therapy (ART) on HIV clinical outcomes: results from the HPTN 052 randomized clinical trial - Beatriz Grinsztejn

Summary - Myron Cohen

Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study - Michael C Thigpen

Antiretroviral Pre-Exposure Prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP Study - Jared Baeten



Rapporteur reports

Community Advisory Group report by Simone Marcotullio


Treatment as prevention :  Results from HPTN 052 (MOAX01) – So, finally «Treatment is prevention». M Cohen, S Esheleman, M C Hosseinipour, B Grinsztejn - The study demonstrated with overwhelming evidence that early ART prevented transmission of HIV in sero/discordant couples and ART reduced the number of clinical events observed. This could be seen as a good rationale for the “Test and Treat" strategy and the management of HIV discordant couples.
In particular, the randomized study showed that early ART (350-550 CD4 versus delayed <250) suppressed viral replication and led to 96% reduction of sexual transmission of HIV-1 in 1763 serodiscordant heterosexual couples. Linked transmissions were 1 (early arm) versus 27 (delayed arm) p ,0.0001, unlinked transmission 11. The non-African sites had a shorter time to ART initiation compared to the African sites - a median of 3.25 years compared to 4.1 years or a 40% higher hazard of initiation. There was no difference across the regions for reasons for ART initiation with the majority initiating ART for CD4 decline. Moreover, immediate ART was associated with 41% reduction in HIV-related clinical events and ART therapy was well tolerated in this wide range of high CD4 population. Rates of serious lab abnormalities and adverse events were low.



Track A report by Valentina Svicher


During this session, results from the HPTN052 trial were presented. In this trial, 1,763 HIV-infected subjects were enrolled mostly from Sub-Saharan Countries, Asia and Latin America, and were randomized to receive early versus delayed antiretroviral therapy according to their CD4 cell count at study-entry. Each patient has a HIV sero-negative partner. The HPTN052 trial was aimed at evaluating the effect of early versus delayed therapy on:
-          Prevention of sexual HIV transmission from HIV-infected adults to their HIV-uninfected partners. Dr Cohen showed that early-therapy is correlated (in multivariate-analisys) with a 96% decreased rate of transmission events compared to delayed-therapy. Intra-couple transmission events were determined by phylogenetic analysis  and by using a Bayesian analysis as presented by Dr Eshleman.
-          Immunological and virological disease progression and response to ART. Dr Hosseinipour showed that patients on early and delayed therapy had high and similar rate of virological-suppression (HIV-RNA<400 copies/ml at 1 year of treatment: 90% vs 93%) and immunological-recovery (mean CD4-count increase at 1 year: 158 vs 191 cells/ul). Dr Hosseinipourn also showed that baseline characteristics  and sexual behavior may help explaining the higher rate of transmission events observed in delayed arm from Sub-Saharan Countries.
-          Clinical outcome of HIV infection. Dr Grinsztejn showed that early treatment correlates with a 41% reduced risk of HIV-related clinical events, in particular of extra-pulmonary tuberculosis.
Dr Cohen concluded that these results should be taken into account for the “Test and Treat” Strategy and to improve the management of HIV sero-discordant couples.

During results, preliminary results from the TDF2 study were also presented. This study showed that daily TDF was effective and safe for prevention of HIV-infection among heterosexual women and men. Similarly, results from the Partner Prep Study showed that TDF and TDF+FTC reduce risk of HIV transmission to uninfected partners by 62% and 73%, respectively.




Track B report by Annie Luetkemeyer


The HPTN 052 study investigated the effect of ART on HIV transmission in 1730 HIV serodiscordant couples.   The HIV-infected partners, (CD4 of 350-550 cells/mm3) were randomized to immediate ART or ART deferred until CD4 < 250 or an AIDS defining illness event.  As presented in more depth in the Track A summary, immediate ART reduced HIV transmission by 96%.
In terms of virologic and immunologic outcomes, after one year of ART, 90% of participants randomized to immediate ART attained HIV RNA < 400 copies/ ml with  a mean CD4 increase of 158, from a median baseline of 442. In the deferred ART arm, 21% of participants initiated ART after a median of 3.5 years and 93% attained VL <400 after one year.  75% started ART due to CD4 count decline, with a median CD4 225 at time of start and a mean increase of 191. Virologic failure was uncommon in both arms,  5.1% in immediate, 2.7% in delayed arm (nb: delayed arm received  shorter overall duration of ART)
A disproportionate number of transmission events occurred at African sites (82%), where 54% of participants were enrolled.  Some possible explanations include more frequent unprotected sex (9 vs. 4%, p=0.007 ) or more frequent sexual activity (29 vs 18% with ≥ 3 sex acts/week, p<0.001 ) in African vs Asian/American enrollees. The HIV infected partner was more frequently female at African sites ( 58 vs. 40%, p<0.0001)
HPTN 052 provided an opportunity to address the “when to start” ART in a randomized population with CD4 count over 350. Immediate initiation of ART was associated with a 41% reduction in clinical events (death, WHO stage 4 disease, pulmonary TB, or severe bacterial infection, p =0.01).  Much of the difference was driven by lower rates of extrapulmonary TB in immediate (3 cases) vs. deferred arms ( 17 cases). Preventative therapy with of TMP/SMX (7%) and isoniazid was similar and infrequent in both arms. Rates of serious lab abnormalities (27% vs 18%) and adverse events (14% vs. 14%) were low in both immediate and deferred arms.



Track C report by Danielle Haley


This session provided detailed data from three landmark studies (HTPN 052, TDF2 and Partners in PrEP) that have definitively demonstrated that ARV provision can prevent HIV transmission from HIV-infected individuals to their uninfected partners. In the case of HPTN 052, the HIV-infected partner was provided combination antiretroviral therapy (cART). Both TDF2 and Partners in PrEP evaluated the efficacy of PrEP prophylaxis in HIV-uninfected individuals.

HPTN 052 Results:

Myron Cohen reported the HPTN 052 results.  The study found that HIV-infected men and women in serodiscordant couples had a reduced risk of transmitting the virus to their uninfected sexual partners by 96% through early initiation of cART. It is the first randomized clinical trial to definitively demonstrate that administration of antiretroviral therapy to an HIV-infected individual can reduce sexual transmission of HIV to an uninfected partner.

Susan Eshleman discussed the procedures for determining linkage status of new HIV infections in HPTN 052. Nearly one fifth of the seroconversion events were unlinked (not associated with primary partner). This underscores the importance of assessing the genetic linkage of seroconversion events in HIV prevention studies.

 

Mina Hosseinipour presented treatment and prevention outcomes of early (CD4 350-550/mm3) versus delayed initiation of ART (repeated CD4 < 250>200/ mm3 or AIDS defining illness). There were regional differences among study participants; however, participants on ART in both arms demonstrated high rates of virologic suppression and CD4 increases. Subjects with delayed ART had lower absolute CD4 one year post-ART initiation.

 

Beatriz Grinsztejn compared clinical outcomes of early versus delayed initiation of ART among HIV-1 infected individuals in HPTN 052. Early initiation of ART reduced the risk of clinical events, especially extrapulmonary tuberculosis. Longer follow-up is necessary to define other complications from delay of therapy.

TDF2 and Partners in PrEP:

Michael C Thigpen reported on the efficacy of daily oral tenofovir use for the prevention of HIV infection in heterosexually active young adults in Botswana. The study found 62.6% efficacy (CI: 21.5-83.4) of tenofovir using intent to treat analysis and 77.9% efficacy (CI: 41.2-93.6) when accounting for treatment interruptions. There were no differences in adherence, sexual behavior or safety data across groups. However, there was significant loss to follow-up in both study arms (>30%), which could influence study findings.

Jared Baeten presented efficacy data from an antiretroviral Pre-Exposure Prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP Study, a three arm trial evaluating TDF or FTC/TDF against placebo. The study found that both regimens were efficacious for both men and women, and found 62% efficacy for TDF (CI:34-78) and 73% (CI:49-85) efficacy for FTC/TDF.

Major Themes and Audience Discussion: Study results demonstrated that treatment can serve as prevention, both through provision of PrEP for uninfected individuals and through early ART for HIV-infected individuals in serodiscordant couples. In the case of all three studies, participants in the control arm will be provided ARVs and will be followed based on a revised study protocol. In light of this data, and the reality of limited resources and access to ARVs, steps must be taken both to determine priorities for ARV provision (prevention vs. treatment) and to implement roll-out of this important HIV prevention strategy.

 




   

    The organizers reserve the right to amend the programme.


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