Largest ever HIV prevention study delivers sobering message

first_img Click to view the privacy policy. Required fields are indicated by an asterisk (*) Largest ever HIV prevention study delivers sobering message Email By Jon CohenMar. 11, 2019 , 3:55 PM Kim Cloete Sign up for our daily newsletter Get more great content like this delivered right to you! Countrycenter_img Community health workers with the Population Effects of Antiretroviral Therapy to Reduce HIV Transmission study did door-to-door HIV testing of 1 million people annually for 3 years. SEATTLE, WASHINGTON—The recipe for ending HIV epidemics seems straightforward. Introduce widespread testing. Immediately put those who test positive on antiretroviral (ARV) drugs, which suppress the virus to undetectable levels so those people won’t infect others. The number of new infections will drop, and the epidemic will peter out.But massive, costly studies done in the past few years have failed to show this strategy can reliably curb the spread of the virus, to the frustration of researchers. The latest and largest ever study presented here last week at the Conference on Retroviruses and Opportunistic Infections did show a modest benefit. But confusingly, there was almost no decline in infections in the study group where it was most expected.Ending the HIV/AIDS epidemic may be harder than anticipated, it seems. “ARVs on their own are not the magic bullet,” says Collins Iwuji, an epidemiologist at Brighton and Sussex Medical School in the United Kingdom who helped run one of the earlier studies, a South African treatment as prevention (TasP) trial. Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe The new study, called Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART), included 1 million adults in Zambia and South Africa. When it began in late 2013, research had shown that ARVs can not only stave off disease, but also prevent people from infecting others. But whether these benefits would translate from an individual to an entire community was unclear.PopART randomized 21 communities into three arms. One received annual house-to-house HIV testing and immediate treatment for those infected (A); another got the same testing, but treatment followed existing country guidelines and was offered only to HIV-infected people who already had evidence of some immune damage (B); and the third got no intervention from the study (C).After 3 years, an analysis that sampled more than 12,000 people in each of the three arms found group B had 30% fewer new infections than group C. But in arm A, where presumably even more people were treated, the researchers found only 7% fewer infections than in arm C, which wasn’t a statistically significant difference. “When we first saw the results we thought it was the other way around, that arm A and B results got reversed,” says Richard Hayes of the London School of Hygiene & Tropical Medicine, who headed PopART. “We had four statisticians review the data. It’s true I’m afraid.”“We have a lot of work to do” to explain the unexpected outcome, he adds. Among the factors that could have boosted the infection risk in A are migration of infected people, clustering of sexual networks that had highly infectious individuals, or more sexual risk taking.François Dabis, who heads the French Agency for Research on AIDS and Viral Hepatitis in Paris and was the principal investigator of the earlier TasP study, says he’s heartened that PopART at least found an impact in arm B. TasP compared immediate treatment with treatment according to South African guidelines; the results, published last year, showed no population benefit from immediate treatment at all, likely because many people who tested positive didn’t seek the free care available.SEARCH, a large study staged in Kenya and Uganda that used health fairs to do community-wide testing, had more success getting infected people on treatment. But SEARCH investigators reported last summer that they, too, had come up empty-handed. In the middle of the trial, the two countries adopted new World Health Organization (WHO) guidelines recommending that all HIV-infected people get treatment immediately, effectively robbing the study of its control group. (WHO’s recommendations complicated analyses in PopART and TasP as well.) A fourth study in Botswana did find a 30% drop in new cases from widespread testing and treatment, but it had far fewer people and barely reached statistical significance.Diane Havlir of the University of California, San Francisco, one of SEARCH’s principal investigators, welcomes one clear message from the studies: that widespread testing has the power to identify the majority of infected people, an essential component of the “Ending AIDS” agenda. “We are one step closer and have data for the next steps,” Havlir says.Nor is anyone ready to give up on universal treatment. “We’re not going in the wrong direction,” Dabis says. “What we’re saying is it’s more complex to achieve reductions in incidence than we anticipated.” Like many others, he says offering ARVs as pre-exposure prophylaxis to people at high-risk of infection is a key missing component of these studies.“But we have to be humble,” Havlir says. The four studies, which together cost more than $200 million, failed to clarify a central question: What percentage of infected people needs to start treatment and completely suppress HIV for an epidemic to peter out? Based on a mathematical model, the Ending AIDS campaign promoted by the Joint United Nations Programme on HIV/AIDS set 2020 goals of getting 90% of infected people to know their status, 90% of that group to be on treatment, and 90% of those to have undetectable virus levels. PopART’s A and B arms both reached this triple target, as did SEARCH and the Botswana study.But perhaps it wasn’t enough. “Ninety-ninety-ninety was an advocacy slogan that got translated into programmatic goals,” says Kevin DeCock, a Kenya-based epidemiologist with the U.S. Centers for Disease Control and Prevention in Atlanta who was on PopART’s scientific advisory board. “It remains to be shown what epidemiologic control is. We’re not out of the woods.”last_img read more