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New battles focus on prevention

Reducing HIV transmission and curbing discrimination against the groups most vulnerable to infection are challenges in stemming the epidemic, which continues to spread

Sergio Lima / Folhapress Young man who lives in a community of about 150 people with HIV, maintained by the nongovernmental organization FALE (Fraternidade Assistencial Lucas Evangelista), in the neighborhood of Recanto das Emas, Federal DistrictSergio Lima / Folhapress

In February 2017, two medical research and treatment centers in São Paulo, one in Rio de Janeiro, and another in Porto Alegre are slated to begin selecting participants for an international study that will evaluate a drug to prevent AIDS. Interested candidates must be HIV negative and must also belong to one of two high-risk groups: men who have sex with men (gays and bisexuals) and transgender women (people who identify as female although they were assigned to the male gender at birth). The study aims to assess the effectiveness of cabotegravir, an injectable antiretroviral drug named after its active ingredient. If it works satisfactorily, twice-monthly injections of the drug may replace the medicine currently used in some countries to prevent HIV transmission and curb the spreading epidemic: a once-daily combination pill containing the antiretrovirals tenofovir and emtricitabine.

AIDS has gone quiet, yet it continues to spread. The disease rarely makes the news these days and, unlike 30 years ago when the epidemic first emerged, it no longer evokes images of hollow-cheeked celebrities with suffering in their eyes. But, as in other countries, the number of new cases is once again trending upward in Brazil – from 43,000 in 2010 to 44,000 in 2015.  This is particularly true among gay men, who were closely associated with the epidemic early on, before the disease had disseminated among heterosexuals, a group where the number of cases is now falling (see graph). A study conducted in the city of São Paulo by a team from the School of Medical Sciences of the Santa Casa of São Paulo (FCM-SCSP) found that one in four men who have sex with men was infected with HIV or the syphilis bacteria, which causes another sexually transmitted disease (STD). “We see young homosexuals in poor living conditions whose personal stories are marked by discrimination and sexual and police violence,” says physician and epidemiologist Maria Amélia Veras, FCM-SCSP professor and study coordinator.

This is true not only in Brazil. “Men who have sex with men, especially younger ones, underestimate the risk of acquiring HIV,” said physician Hyman Scott, professor at the University of California, San Francisco, speaking at one of the sessions at HIV Research for Prevention (HIVR4P), an international conference held in Chicago in late October 2016. Given this status quo, the current trend among researchers, healthcare providers, and health administrators worldwide is to underscore HIV prevention strategies for people who run a high risk of infection because they live among HIV positives.

Rafael Andrade / Folhapress Leandro Fernandes Jacob, from Rio de Janeiro, is HIV positive and has given lectures about his life experiences to players from a number of soccer teamsRafael Andrade / Folhapress

In December 2013, Brazil’s Ministry of Health handed down a decision stipulating that anyone diagnosed with HIV should begin treatment immediately. Consequently, in 2014, the public health system began providing 73,000 people with antiretrovirals, sometimes called the “AIDS cocktail.” The figure was 74,000 in 2015 and 58,000 through October 2016, bringing the total number of people under treatment in Brazil to 489,000 by October 31, 2016. “Among those receiving treatment, 90% have an undetectable viral load, which reduces HIV transmission,” says physician and epidemiologist Adele Benzaken, director of the Ministry of Health’s Department of STD, AIDS and Viral Hepatitis. According to her, the ministry buys and distributes 700 million male condoms free of charge each year – an option that likewise lessens the risk of HIV infection.

Impasses
One of the most-talked-about prevention strategies at present is the use of antiretrovirals by people who do not have the virus but might acquire it through sexual contact with HIV positives. The drug that introduced pre-exposure prophylaxis, or PrEP – as the approach is called – combines tenofovir and emtricitabine in a single pill. In 2012, it was approved for use in the United States, where 80,000 people have adopted it as an additional form of protection against HIV infection. PrEP can be nearly 100% effective and has few side effects (generally nausea and stomach pain), but experts warn that its use should supplement rather than replace other forms of prevention, like condoms, which have played a major role since the onset of the epidemic in the 1980s.

“PrEP is not a magic bullet,” said Carl Dieffenbach, director of the Division of AIDS at the U.S. National Institute of Allergy and Infectious Diseases (NIAID), during a conversation with journalists before the opening of the conference in Chicago. According to Dieffenbach, adhesion is low and people generally stop taking the medicine for two reasons. First of all, those who are not HIV positive consider themselves healthy and therefore can easily forget that the drug has to be taken every day (the alternative is to take it on an as-needed basis in the form of two pills up to two hours before having sex, another pill 24 hours later, and a fourth one 48 hours later). The second reason is that people who take, or could take, PrEP are often concerned that they might suffer social discrimination if they are seen as HIV positive, since this combination of drugs is also used to treat those already infected.

Dario Oliveira / Código 19 / AE With the sponsorship of government agencies and NGOs, travestis distribute condoms and leaflets outside the São Paulo Museum of Art on Gay Pride Day in December 2015Dario Oliveira / Código 19 / AE

A variety of factors make access to HIV prevention drugs challenging in Brazil. In 2014, the company that makes the tenofovir/emtricitabine combination pill – sold under the brand name Truvada and already in use in Brazil to treat people who have AIDS – requested that ANVISA, the Brazilian Health Surveillance Agency, also approve the drug for use by people who are HIV negative. No decision has been handed down yet. When asked by Pesquisa FAPESP, ANVISA said the request “is being given priority consideration.” Two other pharmaceutical firms also await a response to their applications to register the two-drug formula for preventive purposes. At the International AIDS Conference held in Durban, South Africa, in July 2016, a team comprising members from the Ministry of Health, the Oswaldo Cruz Foundation (Fiocruz), and Harvard University presented a paper showing that preventive treatment could cut the cost of providing health care to people with AIDS by 30%.

“There’s still resistance, but the scientific evidence of the benefits of PrEP is so sound today that some cities, like San Francisco, and even some countries, like France, have adopted it as an HIV prevention strategy, and the World Health Organization also recommended it in 2015,” says infectious disease specialist Esper Georges Kallas, professor at the University of São Paulo School of Medicine (FM-USP). Kallas took part in the first international clinical trial, called iPrEx, which proved the strategy effective. The results, published in The New England Journal of Medicine in 2010, indicated that daily use of tenofovir and emtricitabine by 2,499 men and transgender women who have sex with men in six countries decreased transmission of the virus by 44% when used in combination with other prevention measures, such as risk-reduction counseling, frequent HIV testing, condom use, and the treatment of other STDs.

There are psychological benefits as well. “People who enroll in trials, receive PrEP, and take other preventive precautions report that they experience a reduction in fear and anxiety about having sex,” says psychologist and FM-USP researcher Natália Barros Cerqueira, based on her work as a counselor of at-risk individuals. Cerqueira coordinated the USP team of what is referred to as the PrEP Brasil study, which recorded a 61% adhesion rate to this preventive method among 1,187 participants (mainly among those with a higher educational level), who were treated in São Paulo, Rio de Janeiro, Porto Alegre, and Amazonas. According to an article published in August 2016 in AIDS and Behavior, PrEP Brasil found that young people and those with a lower educational level had a need for greater information.

Cerqueira is one of the coordinators of the USP team of HPTN 083, an international study led by the HIV Prevention Trials Network. In February 2017, the team will begin its efforts to recruit a forecast total of 584 participants at four research centers in Brazil: USP, the São Paulo State Department of Health’s Reference and Training Center on Sexually Transmitted Diseases and AIDS (CRT-AIDS), Fiocruz, and Conceição Hospital in Porto Alegre. The study will be conducted at 43 research centers in eight countries and expects to enroll 4,500 men who have sex with men (half under the age of 30) and transgender women who have not yet put in breast implants, which could impair the action of the injectable medicine.

In addition to HPTN 083, the Fiocruz team is planning two other clinical studies. The first will evaluate the safety and efficacy of monthly intravenous injections of the antibody VRC01 for HIV prevention. The second will examine possible interactions between prevention drugs and the hormones typically taken by transgender women and travestis [distinct from “transgender woman,” the latter term is preferred by some assigned males who identify as female in Brazil]. “If there’s an interaction and these people have to choose, they might choose the hormone,” cautions infectious disease specialist Beatriz Grinsztejn, Fiocruz researcher and study coordinator. One of the studies done by the group found that 31% of travestis and transgender women in the Rio de Janeiro Metropolitan Region are HIV positive. “This is much higher than among other groups affected by the epidemic,” she said.

Healthcare teams are still underprepared to deal with those most vulnerable to HIV infection. “We have to call travestis by their chosen names to move towards ending discrimination, guaranteeing access to healthcare services, and keeping them from abandoning treatment,” advises infectious disease specialist José Valdez Ramalho Madruga, director of the CRT-AIDS research unit in São Paulo. “Success with individual treatment means collective success, because it reduces transmission of the virus to others.” The CRT-AIDS teams serve about 6,000 people at the HIV clinic and another 3,000 at a clinic geared solely to travestis and transgender women; they report 40 new cases of HIV infection each month.

UNICEF / P. Esteve Adolescents at a youth center in Moundou, Chad, take part in extracurricular activities related to HIV prevention, including testing for the virusUNICEF / P. Esteve

Discrimination
People who have a greater risk of transmitting or acquiring an HIV infection – men who have sex with men, travestis, transgender women, prostitutes, drug users, and the homeless – suffer “extreme violation of their rights and difficult access to schools, professional training, and health care,” warns Veras. In July 2016, her group completed an analysis of interviews conducted between November 2014 and October 2015 with 673 travestis and transgender women from seven municipalities in São Paulo. Twenty-six percent declared themselves HIV positive. One out of five respondents reported that they had been taken to a police precinct and jailed for one night or more, even though there was no probable cause or arrest warrant.

Veras and her team have launched two new studies that should uncover more in-depth information on social aspects of AIDS. One will follow 500 members of more vulnerable groups for five years to investigate forms of healthcare access. The other will evaluate the efficacy of a strategy to encourage transgender women to receive medical treatment, with the assistance of other members of the group, called navigators. “Each HIV-positive participant will be assisted by a navigator, who will encourage her to have tests and receive treatment, like a tutor or sister, as a way of reinforcing ties to healthcare services and adhesion to treatment,” Veras says.

Worldwide, the AIDS situation is tragic. “Today, 37 million people don’t know they’re living with the virus and 18 million don’t have access to treatment,” said Mark Feinberg, President and CEO of the International AIDS Vaccine Initiative (IAVI). Cases began rising again after 2011, although the figure had been falling steadily since the onset of the epidemic. About 2 million new HIV infections are now recorded each year, half of them in Africa. In Sub-Saharan Africa, youth from the ages of 15 to 24 account for 40% of new cases, equivalent to 450,000 cases per year or nearly 10,000 per week, according to Kawango Agot, director of Kenya’s Impact Research and Development Organization (IRDO). “Female students have sex with older men, sometimes their own teachers, in exchange for food, clothing, or electronics,” reported Sinead Delany-Moretlwe, director of the Wits Reproductive Health and HIV Institute, in South Africa.

Gideon Mendel / Getty Images Jabu Shezi, HIV-positive community educator, demonstrates condom use to women waiting to receive medical services in the province of KwaZulu-Natal, South AfricaGideon Mendel / Getty Images

The prevention method that has reached the most advanced phase of testing, besides PrEP, is the vaginal ring, a flexible, circular band containing the antiviral dapivirine, which has cut the rate of transmission to women by 60%. The ring, which must be replaced once a month, might prove especially valuable to young women in Africa, who have been hard hit by the epidemic. Sharon Hillier of the University of Pittsburgh said that adhesion to the vaginal ring has been high and that the women who took part in evaluative testing emphasized that it gave them greater autonomy, because their male partners did not use condoms and they knew they were running the risk of HIV infection. “Nobody sees it, the family doesn’t know about it, the partner doesn’t know about it,” she said.

Since the 1990s, much hope has been placed in finding an HIV vaccine, but a number of experts reported that clinical trials of candidate vaccines have yet to record acceptable efficacy rates, and large-scale use of those currently under evaluation is unlikely. But other strategies are surfacing. Anthony Fauci, NIAID Director, presented the findings of a study performed on 15 monkeys and published in the journal Science in October 2016. If all goes as expected, this research may move towards a new form of AIDS treatment involving the use of antibodies already approved for the treatment of inflammatory bowel diseases, which block the action of α4β7 integrin, a protein that controls CD4 cells, in turn important in fighting HIV. “This is a proof of concept in an animal model, and now we’re planning human testing,” Fauci told Pesquisa FAPESP. “We have to evaluate the safety and efficacy of the drug very cautiously, because it has been approved for another disease, not AIDS.”

In the effort to control the global epidemic, discrimination against gays and people with HIV has proven just as challenging as the drug-resistant nature of the virus. An article published in the journal Lancet in June 2016 and signed by epidemiologist Chris Beyrer of Johns Hopkins University warned about the growing stigmatization of people with HIV and the criminalization of homosexuality in countries like India, Russia, Nigeria, Gambia, and Uganda. On November 23, 2016, The Washington Post reported that the government of Tanzania planned to suspend international programs that provide testing, condoms, and medical care to gays, financed mainly by the United States. In Tanzania, where it is estimated that 30% of gay men are HIV positive, anyone who has same-sex liaisons can be jailed for up to 30 years.

* The journalist traveled to Chicago at the invitation of the global conference HIV Research for Prevention (HIVR4P)

Project
1. 
Implementation of pre-exposure prophylaxis (PrEP) to HIV: A design statement (nº 2012/51743-0); Grant Mechanism Research in public policies for the National Health Care System (PP-SUS); Principal Investigator Esper Georges Kallas (FM-USP); Investment R$ 444,842.91.
2. Vulnerabilities, health needs and access to health services of the transvestite, transsexual and transgender population of the State of São Paulo (nº 2013/22366-7); Grant Mechanism Regular research grant; Principal Investigator Maria Amélia de Sousa Mascena Veras (FCMSC); Investment R$297,076.46.

Scientific articles
GRANT, R. M. et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. The New England Journal of Medicine. V. 363, No. 27, pp. 2587-99. 2010.
SIDDAPPA, N. B. et al. Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy. Science. V. 354, No. 6309, pp. 197-202. 2016.
HOAGLAND, B. et al. Awareness and willingness to use pre-exposure prophylaxis (PrEP) among men who have sex with men and transgender women in Brazil. AIDS and Behavior. 2017.
BEYRER, C. et al. The global response to HIV in men who have sex with men. The Lancet. V. 388, No. 10040, pp. 198-206. 2016.