Pam Harrison

April 11, 2014

CAPE TOWN, South Africa — The number of new HIV infections continues to decline steadily in response to a greater uptake of antiretroviral therapy (ART) by people who are infected with HIV or at risk for infection.

In fact, the tipping point in the AIDS epidemic has been reached, according to Salim Abdool Karim, MD, PhD, director of the Centre for the AIDS Program of Research in South Africa (CAPRISA).

"In the past few years, we have seen evidence for ART that has created new hope for HIV prevention," Dr. Karim said during a plenary session here at the 16th International Congress on Infectious Diseases. "The provision of ART really makes HIV control an achievable milestone."

Until mid-2010, circumcision was the most promising strategy to reduce the sexual transmission of HIV. Then the CAPRISA 004 trial showed that tenofovir gel used before and after sex led to a 39% reduction in the transmission of HIV infection to HIV-negative sexually active women (Science. 2010;329:1168-1174). Although the protective effect was significantly related to good adherence to the regimen, "this was the first evidence we had that ART prevented HIV transmission," Dr. Karim said.

Later that year, the Pre-Exposure Prophylaxis Initiative provided the first evidence that oral ART could prevent HIV transmission in men who have sex with men (N Engl J Med. 2010;363:2587-2599). Investigators showed that the combination of oral tenofovir plus emtricitabine reduced the incidence of HIV by 44% in men or transgender women who have sex with men.

This was followed by 2 separate trials of HIV-discordant heterosexual couples in Africa showing that the daily use of tenofovir plus emtricitabine reduced the incidence of HIV by more than 60%.

In the HPTN 052 trial of HIV-discordant heterosexual couples, HIV-infected partners with a CD4 count from 350 to 550 cells/mm³ were randomized to received immediate therapy (early ART) or to receive no therapy until CD4 cell count declined or HIV-related symptoms emerged (delayed ART) (N Engl J Med. 2011;365:493-505). HIV-infected partners who received early ART were 96% less likely to transmit the virus to their uninfected partner than those who received delayed ART.

Although not discussed by Dr. Karim, results from the PARTNER trial, presented at the 2014 Conference on Retroviruses and Opportunistic Infections (abstract 153LB), found no HIV transmission between discordant homosexual or heterosexual partners who did not use condoms after an estimated 44,500 sex acts, provided that the HIV infected partner maintained viral suppression.

"There is no doubt in my mind that treatment is a key part of our prevention strategy," said Dr. Karim. ART provides "the HIV-negative partner with a high level of protection, as long as she or he is faithful."

In 2013, the pre-exposure prophylaxis strategy was shown to offer significant protection to people exposed to HIV through injection drug use (Lancet. 2013;381:2083-2090). In that study, the risk for transmission was reduced by 49%, Dr. Karim reported.

High Coverage Rates

 
That's what I want. I want to end AIDS. Dr. Abdool Karim
 

High coverage rates of ART not only reduce viral transmission between discordant couples, they also significantly increase overall survival. In a population cohort of more than 100,000 people living in rural South Africa, investigators reported that adult life expectancy in 2003 — the year ART became available in the region — was only 49.2 years. By 2011, adult life expectancy had increased to 60.5 years. The 11.3-year gain was largely attributable to high rates of ART coverage (Science. 2013;339:961-965).

"I have never in my life seen these kinds of changes in life expectancy," Dr. Karim said. "You have to have major upheavals in society to get the same kind of increases as we are seeing with ART, so there are enormous benefits coming from the provision of antiretrovirals." There are, of course, equally enormous challenges before society ever reaches the end-of-AIDS milestone, he acknowledged.

HIV continues to spread at high rates in some areas. In rural South Africa, approximately half of all women are infected with HIV by the age of 24. And HIV rates continue to be high in men who have sex with men and in injection drug users.

But the biggest challenge, according to Dr. Karim, is dealing with the stigma that prevents people from accessing care that is known to prevent the sexual transmission of HIV infection, such as circumcision, condoms, pre- and post-HIV exposure prophylaxis, and early initiation of ART.

"Even if we did nothing different — if we just continue on the same trajectory that we're now on — we will continue to gain the benefits of a decline in the numbers of new infections and HIV incidence," Dr. Karim explained. "But if we were to add new strategies and implement them to scale, we could increase that decline substantially. That's what I want. I want to end AIDS."

Treatment as Prevention

The treatment as prevention strategy works, said Julio Montaner, MD, DSc, architect of the strategy and director of the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, Canada.

After ART was rolled out in British Columbia, the data unexpectedly showed that as a steady state was reached in terms of the number of patients receiving highly active ART, the number of new infections dropped, he told Medscape Medical News.

"All this was happening against a background of rapidly increased syphilis rates in the community, so we reasoned that ART was the only way to explain this significant change," he reported.

Subsequent cost-effective modeling showed that initiating treatment at diagnosis would save money because there would be dramatic benefits for people infected with and those at risk for HIV.

That is exactly what happened in British Columbia, as Dr. Montaner and his colleagues report in a recent analysis (PLoS One. 2014;9:e87872). From 1996 to 2012, new HIV diagnoses declined by 66% as the province expanded its highly active ART program. And there was an estimated 42% decline in HIV incident cases per year during the same period.

"Not only do I fully support Dr. Karim's optimism about having reached a tipping point in the AIDS epidemic," said Dr. Montaner, "but the new WHO guidelines have provided us with a fantastic framework for optimally deploying the guidelines at the field level. Work we have done, among others, clearly demonstrates that, if we fully embrace and optimally implement these guidelines, we will see a dramatic reduction in morbidity, mortality, and HIV transmission everywhere, provided it's done properly. There is absolutely no doubt in my mind that treatment today offers the best opportunity to prevent morbidity and mortality from HIV infection and, secondarily, a decrease in new HIV infections."

Dr. Karim and Dr. Montaner have disclosed no relevant financial relationships.

16th International Congress on Infectious Diseases (ICID). Presented April 3, 2014.

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