New directions home: Aligning HIV treatment, prevention

Advances in HIV treatment since 1996, when potent antiretroviral drug combinations became available, are well known. HIV infection can now be considered a chronic disease for those with access to care. However, success in HIV prevention has seemed a harder battle.

Clinical trials to prevent HIV spread through education and behavioral efforts have seldom had dramatic results, and political barriers have blunted the effect of proven methods such as condom use and clean needle access for drug injectors. This bleak picture is, fortunately, changing radically in a series of developments that rival the excitement of antiretroviral therapy itself.

Treatment is prevention

The first ray of hope and still a key tool was the recognition that male circumcision is effective in reducing the transmission and acquisition of HIV and other sexually transmitted infections. During the past 2 years, even more excitement centers on the interface between treatment and prevention. In fact, many prevention strategies now utilize the same antiretroviral drugs in new ways to limit transmission or acquisition of HIV with striking effects, especially for those most medication-adherent.

Many people, particularly women, cannot safely negotiate sexual relationships to prevent HIV exposure but could protect themselves with a self-administered device or microbicide. Cervical diaphragms have not been found effective, and female condoms are obvious to a male partner not willing himself to use barrier protection. Vaginal microbicides, typically gels inserted before or after intercourse, are attractive targets of prevention research. Vaginal gels of several products repeatedly failed to show any real benefit, until the truly dramatic presentation of the CAPRISA 004 trial at the AIDS meeting in Vienna in 2010.

This study used for the first time an antiretroviral drug, tenofovir, as a 1% vaginal gel applied 12 hours before and 12 hours after sexual intercourse. HIV transmission was reduced by approximately 40% or more in women who reported the highest rates of appropriate use. For the first time, a woman had at least one self-administered tool to prevent HIV infection, and the scientific presentation was greeted by a prolonged standing ovation — almost unheard of at an otherwise staid research conference. This promises to be a very inexpensive product and is also being considered for rectal administration.

PREP and iPrEx trials

Pre-exposure prophylaxis, or PREP, is another prevention approach designed to reduce infection risk for those who can’t or won’t demand condom protection or potentially for injection drug users without clean needle access. Here, oral antiretroviral drugs are prescribed for the uninfected person and used either continuously or at the time of exposure. This long-debated concept was shown to be effective in another landmark study, iPrEx, published in late 2010.

Here, very high-risk but HIV uninfected men who have sex with men were prescribed a fixed-dose combination of tenofovir and emtricitabine and assigned the combination daily during the entire trial.

Again, the results were striking and successful. Overall, PREP was more than 40% effective, with even higher success (68%) in those who reported more than 90% medication adherence. In fact, plasma and cellular drug levels suggest almost complete protection in adherent participants.

This trial, named one of the scientific breakthroughs of 2010 by Time magazine, was followed by three similar research efforts in heterosexuals. The first, still unpublished, was not successful. However, recently, two additional PREP trials have also shown PREP effects similar to iPrEx.

Together, the vaginal microbicide and PREP applications of antiretroviral drugs to prevent HIV-infection have changed the face of prevention, allowing an individual at least some control over the risk of becoming infected.

HPTN 052

We have long known that starting antiretroviral drugs during pregnancy can effectively block transmission of HIV from infected women to newborns and that sexual transmission is minimal in those with naturally low plasma viral titers. Although many have expected that ART would similarly reduce sexual spread, this was recently proved in a prospective clinical trial, known as HPTN 052.

In this African trial, serodiscordant heterosexual couples agreed that the infected partner would either begin ART earlier than local guidelines suggested or wait until that point in the disease stage.

The results, first announced at the IAS conference in Rome this summer, indicated a striking reduction in HIV transmission (96%) and also a lower rate for tuberculosis, the most common infection associated with HIV in that part of the world.

These results are accelerating efforts to identify and treat all HIV-infected people and to start treatment regardless of the CD4 cell count, with the goal that community-wide antiretroviral coverage will decrease HIV incidence in the general population. Already, several cities, including Vancouver and San Francisco, have promoted this as a public health policy, and testing of this as a strategy is being conducted in several cities, including Washington D.C. — the city with the highest rates of new HIV-infection in our country.

The future

Where does all of this lead us as we seek to bring the HIV pandemic under control? We clearly have potent new prevention methods, but individually, each has limitations.

Microbicides and PREP only work in those able to achieve and sustain excellent adherence. Treating HIV to reduce the viral load and, thus, transmission, requires finding and treating all or most of the 200,000 or so cases of HIV-infected people not already in care — a daunting task — and maintaining full viremia suppression in all of those in care — also not an easy goal, given adherence problems and other barriers. The cost of universal treatment in resource-limited settings is obviously a real challenge in times of global economic distress.

Finally, troubling evidence suggests that although HIV transmission may be coming under control, especially in the gay community, the incidence of other STIs, particularly syphilis, are again accelerating.

We are excited by the new potential control of HIV, but must not expect that antiretroviral drugs will alone be sufficient or that we can ignore the crucial alliance between the infectious diseases and public health communities that will be needed to arrive at our ultimate goal of an HIV-free home.

Paul A. Volberding, MD, is chief of medical service at San Francisco Veterans Affairs Medical Center; professor and vice-chair of the department of medicine and co-director of the Center for AIDS Research at the University of California San Francisco and is the Chief Medical Editor of Infectious Disease News. Disclosure: Dr. Volberding is an adviser to BMS and on data and safety monitoring boards for Gilead, TaiMed and the NIH.

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