127:
trial there was a statistically significant lower rate of infection in the vaccine group compared to the placebo group, with p=0.04 for the "modified intent to treat" analysis that excluded persons who were found to have HIV infection after enrollment but before the first vaccination. However, by the other two methods of analysis, there was no statistical significance in infection rates between the vaccine and placebo groups, with p=0.08 for the "intent to treat analysis" including all persons originally enrolled in the trial, and p=0.16 for the "per protocol analysis" including only persons from the modified intent to treat group who completed all three vaccinations and subsequent screening. Additionally, the vaccine regimen had no effect on the amount of virus in the blood of volunteers who became HIV-infected during the study.
82:. Eligibility criteria for participation in the study required that all volunteers be HIV negative prior to enrollment in the study and be willing to participate in educational counseling intended to teach ways to reduce risk behavior associated with contracting HIV. After being vaccinated, volunteers were asked to receive HIV testing every six months for three years, as well as receive additional risk-behavior counseling at every testing visit.
680:
Pitisuttithum, P.; Rerks-Ngarm, S.; Bussaratid, V.; Dhitavat, J.; Maekanantawat, W.; Pungpak, S.; Suntharasamai, P.; Vanijanonta, S.; Nitayapan, S.; Kaewkungwal, J.; Benenson, M.; Morgan, P.; O'Connell, R. J.; Berenberg, J.; Gurunathan, S.; Francis, D. P.; Paris, R.; Chiu, J.; Stablein, D.; Michael,
448:
Burton, DR; Desrosiers, RC; Doms, RW; Feinberg, MB; Gallo, RC; Hahn, B; Hoxie, JA; Hunter, E; Korber, B; Landay, A; Lederman, MM; Lieberman, J; McCune, JM; Moore, JP; Nathanson, N; Picker, L; Richman, D; Rinaldo, C; Stevenson, M; Watkins, DI; Wolinsky, SM; Zack, JA (16 January 2004). "Public health.
622:
Rolland, M; Edlefsen, PT; Larsen, BB; Tovanabutra, S; Sanders-Buell, E; Hertz, T; deCamp, AC; Carrico, C; Menis, S; Magaret, CA; Ahmed, H; Juraska, M; Chen, L; Konopa, P; Nariya, S; Stoddard, JN; Wong, K; Zhao, H; Deng, W; Maust, BS; Bose, M; Howell, S; Bates, A; Lazzaro, M; O'Sullivan, A; Lei, E;
126:
During the study, 125 of the 16,402 participants contracted HIV through behavior unrelated to their study participation. Of those 125, 74 infected persons had received placebo and 51 had received the vaccine, or 31.2% reduction. By one of the three pre-decided statistical tests for analysis of the
319:
Rerks-Ngarm, S.; Pitisuttithum, P.; Nitayaphan, S.; Kaewkungwal, J.; Chiu, J.; Paris, R.; Premsri, N.; Namwat, C.; De Souza, M.; Adams, E.; Benenson, M.; Gurunathan, S.; Tartaglia, J.; McNeil, J. G.; Francis, D. P.; Stablein, D.; Birx, D. L.; Chunsuttiwat, S.; Khamboonruang, C.; Thongcharoen, P.;
37:
between 2003 and 2006. It used a combination of two HIV vaccines that had each failed in earlier trials. Participants were vaccinated over the course of 24 weeks beginning in
October 2003 and were then tested for HIV until July 2006. The results of the study were publicized in September 2009. The
262:
A modified version of the vaccine regimen tested in
Imbokodo was evaluated in the Mosaico trial (HVTN 706/HPX3002), which began in 2019. This trial enrolled nearly 3,900 men who have sex with men and transgender people in the Americas and Europe. In 2024, the Mosaico DSMB determined the regimen
226:
Supported in part by an
Interagency Agreement (Y1-AI-2642-12) between the U.S. Army Medical Research and Materiel Command and the National Institute of Allergy and Infectious Diseases and by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of
130:
Immediately after release of the results, there was controversy and dispute over the significance of these results raised by several researchers, who also questioned the unusual strategy of pre-releasing the conclusion of vaccine efficacy to the press before publication of the actual data in a
258:
A similar combination of two HIV vaccines, a vector-based vaccine and a recombinant protein vaccine, was tested in the
Imbokodo study (HVTN 705/HPX2008) in Africa between 2017 and 2021. The primary analysis found the vaccine safe but with low efficacy (25.2%, not statistically significant) in
89:
calling into question the rationale for this study of combining two vaccines that each failed in prior human trials to generate immune responses that they were designed to elicit. This letter stated that spending $ 119 million when "the overall approval process lacked input from independent
242:, which itself is a spin-off company of Genentech founded for the purpose of developing AIDSVAX. Global Solutions for Infectious Diseases, a nonprofit organization coāfounded by former VaxGen executives, has ownership of certain intellectual and manufacturing rights of AIDSVAX.
45:
The trial collaborators have stated that results of this trial give the first supporting evidence of any vaccine being effective in lowering the risk of contracting HIV. On
October 20, 2009, the organizers released full results of the study through publishing in the
186:
The immune responses of uninfected patients could point the way to more fruitful research. Nelson
Michael, director of the U.S. Military HIV Research Program who ran the trial, says that results lend "biological credence to the initial clinical study results".
98:
Over six months, volunteers received a prime-boost vaccination including six injections, four injections of a vaccine called ALVAC HIV (vCP1521) with the last two being at the same time as two injections of another vaccine called AIDSVAX B/E (gp120).
623:
Bradfield, A; Ibitamuno, G; Assawadarachai, V; O'Connell, RJ; deSouza, MS; Nitayaphan, S; Rerks-Ngarm, S; Robb, ML; McLellan, JS; Georgiev, I; Kwong, PD; Carlson, JM; Michael, NL; Schief, WR; Gilbert, PB; Mullins, JI; Kim, JH (Oct 18, 2012).
182:
were 54% more likely to become infected, but no more susceptible than trial subjects receiving the placebo. However, these studies all emphasize that such post-hoc analyses are subject to inherent bias and must be interpreted with caution.
254:
was started in South Africa. It tested a combination of two HIV-vaccines which were slight modifications of those used in the RV 144 trial. The trial was stopped early in 2020 because no evidence of efficacy was seen.
166:
in
Washington DC tested the blood of trial subjects for different immune indicators between those who received the vaccine and contracted HIV (41 subjects) and those who did not become infected (205 subjects).
227:
Military
Medicine and the U.S. Department of Defense. Sanofi Pasteur provided the ALVAC-HIV vaccine, and Global Solutions for Infectious Diseases (VaxGen) provided the reagents for the immunogenicity assays.
789:
Adis
International, Ltd (2003). "HIV gp120 vaccine - VaxGen: AIDSVAX, AIDSVAX B/B, AIDSVAX B/E, HIV gp120 vaccine - Genentech, HIV gp120 vaccine AIDSVAX - VaxGen, HIV vaccine AIDSVAX - VaxGen".
259:
preventing HIV infection compared to placebo. The study, sponsored by
Janssen Vaccines & Prevention B.V. and funded by the NIAID and the Bill & Melinda Gates Foundation, is ongoing.
212:
38:
initial report showed that the rate of HIV infection among volunteers who received the experimental vaccine was 31% lower than the rate of HIV infection in volunteers who received the
42:. This reduction was not large enough for the Ministry of Public Health in Thailand to support approving the vaccine; it would have licensed it if the reduction had been 50% or more.
216:
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131:
peer-reviewed scientific journal and lack of explanation regarding the three different statistical evaluations of which two did not yield significant results; Dr.
881:
163:
204:
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ineffective in preventing HIV infection, leading to the trialās discontinuation. No safety issues were identified with the Mosaico vaccine regimen.
90:
immunologists and virologists who could have judged whether the trial was scientifically meritorious" was an ill-advised use of precious resources.
979:
765:
208:
372:
683:"Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand"
740:
85:
Before this vaccine trial was initiated, an opinion letter from 22 established HIV researchers had been published in the journal
906:
856:
48:
974:
220:
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106:
containing genetically engineered versions of three HIV genes (env, gag and pol). The ALVAC vector is an inert form of
574:
135:
defended this by stating that explaining these nuances in the press release "would have confused everybody".
766:"Sanofi Pasteur Commends Results of First HIV Vaccine Study to Show Some Effectiveness in Preventing HIV"
143:
494:"Lessons from the RV144 Thai Phase III HIV-1 Vaccine Trial and the Search for Correlates of Protection"
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636:
115:
114:
B/E is composed of genetically engineered gp120, a protein on the surface of HIV, together with the
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556:
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424:
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The vaccine was found to be safe, well tolerated, and suitable for large-scale further research.
159:
61:
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932:"Janssen and Global Partners to Discontinue Phase 3 Mosaico HIV Vaccine Clinical Trial"
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682:
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73:
30:
510:
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818:
802:
398:
132:
625:"Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2"
560:
478:
681:
N. L.; Excler, J. L.; Robb, M. L.; Kim, J. H. (2011). Kallas, Esper Georges (ed.).
142:
showed that there is a 29% chance that the vaccine is not effective (although this
103:
959:
882:"HIV Vaccine Candidate Does Not Sufficiently Protect Women Against HIV Infection"
707:
79:
27:
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were 43% less likely to become infected. Those who produced envelope specific
321:
60:
A total of 16,402 Thai volunteers aged 18ā30 were recruited to participate in
462:
235:
150:, and cannot be directly compared to the p=.04 from the original analysis).
107:
810:
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519:
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351:
326:"Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand"
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342:
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251:
34:
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147:
111:
39:
373:"HIV Vaccine Study First to Show Some Effectiveness in Preventing HIV"
239:
158:
In a study in September 2011, researchers involved with the trial at
551:
534:
493:
399:"The Moon Landing of HIV Vaccine Research: RV144, Ten Years Later"
175:
174:
antibodies that recognise the V2 loop in the HIV envelope protein
110:, a bird virus which cannot cause disease or replicate in humans.
833:"Prime-Boost Vaccine Study Shows Modest Effect in Preventing HIV"
170:
Their work is not complete, but those in the study who produced
492:
Kim, Jerome H.; Excler, Jean-Louis; Michael, Nelson L. (2015).
72:
study groups, with those in the experimental group receiving a
907:"Failed HIV vaccine trial marks another setback for the field"
449:
A sound rationale needed for phase III HIV-1 vaccine trials".
179:
171:
68:
Provinces in Thailand. These volunteers were randomized into
597:"Clues emerge to explain first successful HIV vaccine trial"
52:
and presented them at the AIDS Vaccine Conference in Paris.
857:"Another HIV vaccine strategy fails in large-scale study"
213:
United States Army Medical Research and Materiel Command
217:
National Institute of Allergy and Infectious Diseases
743:. US Military HIV Research Program. Archived from
375:. US Military HIV Research Program. Archived from
575:"Statisticians review landmark HIV vaccine trial"
425:"For First Time, AIDS Vaccine Shows Some Success"
367:
365:
363:
361:
314:
312:
310:
308:
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8:
223:. The cost of the trial was $ 119 million.
16:Clinical trial of an HIV vaccine in Thailand
164:United States Military HIV Research Program
838:. Global Solutions for Infectious Diseases
320:Robb, M. L.; Michael, N. L.; Kunasol, P.;
238:under a license and supply agreement with
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706:
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341:
205:Surgeon General of the United States Army
138:In May 2011, a new analysis initiated at
230:ALVACāHIV (vCP1521) was manufactured by
272:
960:ClinicalTrials.gov record of the study
741:"MHRP International Network: Thailand"
203:The RV 144 trial was sponsored by the
146:is very different conceptually from a
7:
595:Callaway, Ewen (16 September 2011).
285:"Vaccine protects against HIV virus"
278:
276:
886:National Institutes of Health (NIH)
423:McNeil Jr, Donald G. (2009-09-25).
234:. AIDSVAX B/E was manufactured by
209:Thailand Ministry of Public Health
14:
535:"HIV vaccine results controversy"
511:10.1146/annurev-med-052912-123749
397:Walker, Molly (3 December 2019).
803:10.2165/00126839-200304040-00007
330:New England Journal of Medicine
49:New England Journal of Medicine
980:Clinical trials related to HIV
250:In 2016 the HIV vaccine trial
1:
577:. Medical Express. 2011-05-09
221:National Institutes of Health
708:10.1371/journal.pone.0027837
533:Leavy, Olive (2009-11-01).
283:Dolgin, Elie (2009-09-24).
996:
539:Nature Reviews Immunology
498:Annual Review of Medicine
324:; Moph-Taveg, I. (2009).
102:ALVACāHIV consists of a
463:10.1126/science.1094620
219:, which is part of the
211:with support from the
33:that was conducted in
609:10.1038/news.2011.541
379:on September 27, 2009
343:10.1056/NEJMoa0908492
297:10.1038/news.2009.947
207:and conducted by the
144:posterior probability
975:HIV vaccine research
747:on September 7, 2008
699:2011PLoSO...627837P
649:10.1038/nature11519
641:2012Natur.490..417R
162:in Bangkok and the
94:Vaccine composition
160:Mahidol University
863:. 3 February 2020
336:(23): 2209ā2220.
246:Subsequent trials
154:Cautious optimism
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289:Nature News
80:HIV vaccine
77:prime-boost
28:HIV vaccine
969:Categories
942:2024-04-15
917:2022-06-26
892:2024-04-15
867:2022-06-26
842:2009-09-24
775:2009-09-24
751:2009-09-24
581:2011-05-13
434:2009-09-24
383:2009-09-24
322:Kim, J. H.
267:References
191:Conclusion
24:Thai trial
819:195340148
236:Genentech
108:canarypox
74:phase III
62:Chon Buri
26:, was an
22:, or the
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687:PLOS ONE
667:22960785
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471:14726576
352:19843557
252:HVTN 702
215:and the
199:Sponsors
116:adjuvant
56:Protocol
35:Thailand
936:JNJ.com
718:3244387
695:Bibcode
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451:Science
148:p-value
122:Results
112:AIDSVAX
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20:RV 144
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475:S2CID
176:gp120
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410:2020
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64:and
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