#AIDS2016: From medical circumcision to vaccines, these seven things will change HIV

COMMENT

In 2015, the Joint United Programme on HIV and Aids (UNAids) estimated that there were about 2.1 million new HIV infections globally, translating into almost 67 000 new HIV infections per day. A significant part of the new HIV infections occur among vulnerable populations such as men who have sex with men, transgender individuals, sex workers and people who inject drugs. In most of Africa, young women have the highest rates of new HIV infections.

But considerable progress has been made in preventing new infections over the past 16 years. In 2000, when the 13th International Aids Conference was held in Durban, safer sex practices, also known as the “ABC” strategies, encouraging sexual abstinence, a reduction in the number of multiple and concurrent sexual partnerships (be faithful) and the use of condoms, were among the best strategies we had for HIV prevention.

Since then, HIV researchers have changed the landscape of the epidemic. They have developed new and better prevention strategies that are more effective and easier to implement.

1. Medically circumcised men are half as likely to contract HIV
Clinical trials conducted between 2002 and 2005 demonstrated that medical male circumcision can reduce a man’s risk of HIV by 50% to 60%. Since its wide-scale implementation in 2009, about 10 million men in Eastern and Southern Africa have been medically circumcised to reduce their chances of contracting the virus. About three million men in South Africa were circumcised between 2010 and 2015.

2. A pill that prevents HIV infection
Since 2010, results from clinical trials, starting with the Centre for the Aids Programme of Research (Caprisa) 004 study of tenofovir gel, have shown that antiretroviral drugs that HIV-infected people use to suppress the virus in their bodies can also be used to prevent HIV infection in HIV-negative people. This intervention is called pre-exposure prophylaxis (PrEP). The World Health Organisation now recommends that HIV-negative people who are at high risk of contracting HIV take an antiretroviral pill called Truvada once a day (it contains tenofovir and emtricitabine). Studies have shown that, if taken correctly, the pill can reduce the chances of contracting HIV by more than 90%. The South African government started to provide PrEP to sex workers at selected clinics in June.

3. Antiretroviral treatment prevents the spread of HIV
Studies have shown that antiretroviral treatment doesn’t only allow people with HIV to have longer lives; it also makes them far less likely to transmit the virus through sex. The risk of transmission is very low as antiretrovirals effectively suppress the virus in an HIV-infected person’s body — the amount of HIV in the person’s body becomes so low that tests can’t detect it.

If implemented on a large enough scale, the “treatment as prevention” strategy has the potential to alter the course of the HIV epidemic.

Access to antiretrovirals only became a reality in the developing world, including South Africa, after the Aids Conference in Durban in 2000. Since then, remarkable progress has been made in scaling up antiretroviral treatment. By the end of 2015, 17 million HIV-infected people were on treatment, three million of them in South Africa.

4. Glimmers of hope for an HIV vaccine
The quest for an HIV vaccine began in the 1980s, but there have been many disappointments. Vaccine development faces unique challenges. Firstly, HIV attacks CD4+ T cells, the very cells that orchestrate the immune system to combat intruder viruses like HIV. HIV also continuously mutates and recombines, resulting in an extensive diversity of viral strains. For a vaccine to be effective at a global level, it would have to protect against a large number of evolving and diverse strains of HIV. Vaccines often mimic natural immunity, but there is not a single known case of an HIV-positive person naturally clearing the infection.

In 2009, the RV144 trial demonstrated a modest 31% effect in preventing HIV in Thailand. It provided hope that an HIV vaccine may be possible. A similar vaccine is now being tested in South Africa.

5. Clinical trials with pre-formed antibodies in humans are underway
Unlike active immunisation, where the human immune system is stimulated to produce antibodies, passive immunisation is when a person receives pre-formed antibodies, usually by injection. Animal studies have shown that broadly neutralising antibodies (bNAbs) may be effective against HIV, but this has not yet been shown in humans. The bNAbs that have been isolated over the past few years collectively target one of five conserved neutralisation-sensitive parts of the HIV envelope.

The first efficacy trial of a bNAb known as VRC01 for HIV prevention began enrolling participants in the US and Africa this year.

6. Could the Caprisa antibody be the answer? Trials to start in 2017
In 2013, Caprisa, together with the Vaccine Research Center in the US, identified the bNAb known as CAP256-VRC26.25 from a KwaZulu-Natal woman participating in one of the Caprisa clinical trials. This antibody, which targets the variable loop 2 (V2) region of the HIV envelope, is among the most potent monoclonal antibodies currently available. It neutralises most subtype C viruses, the sub- type that is found in South Africa. In an animal study, this antibody was able to protect monkeys from the monkey equivalent of HIV. The antibody is currently being manufactured in the US for human studies that are set to begin in mid-2017.

7. An injection to prevent HIV offers hope for the future
If broadly neutralising antibodies are shown to be safe and efficacious in humans, they could become a long-acting HIV-specific prevention strategy. The advantage of this approach to taking a pill once a day to prevent HIV is that it wouldn’t require daily administration. Antibodies may also be a first step towards an HIV vaccine. Given the high burden of HIV infection among young women in sub-Saharan Africa and the limited prevention options available, the development of novel HIV prevention technologies like neutralising anti-bodies, which could be administered as a three-monthly injection, could be a game changer in the HIV epidemic in Africa.

Salim Abdool Karim is the director of the Centre for the Aids Programme of Research in South Africa (Caprisa). He is also Caprisa professor of global health at the Mailman School of Public Health at Columbia University, adjunct professor of medicine at Weill Medical College of Cornell University and pro vice-chancellor (research) at the University of KwaZulu-Natal. He is the chair of the UNAids Scientific Expert Panel.

Read more from our special AIDS 2016 report.

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