Achieving an AIDS-free World: Science and Implementation

When AIDS was first recognized in 1981, health professionals were ill equipped to address the emerging pandemic. Opportunistic infections were treated, and supportive care was provided in accordance with the regional availability of healthcare; however, even after HIV was recognized as the causative agent of AIDS, truly effective therapy would not be available for more than a decade. Prevention methods were similarly insufficient, as messages about safe sex and condoms often provedweaker than human impulse. But helplessness has now given way to hope. Basic and clinical scientific advances have yielded powerful therapeutic and preventive interventions. By the end of 2012, 9.7 million HIV-infected individuals worldwide were receiving antiretroviral therapy (ART), and some 4.2 million deaths had been averted during the previous decade in low-income and middleincome countries. These feats were accomplished through the joint efforts of the US President’s Emergency Plan for AIDS Relief; the Global Fund to Fight AIDS, Tuberculosis and Malaria (among other multilateral and bilateral organizations); health practitioners in endemic countries; and community activists worldwide. Combination prevention methods have been applied with striking results (WHO, 2013). For example, programs aimed at the prevention of mother-tochild transmission have proven highly successful (US Department of State, 2013). Voluntary male medical circumcision for the prevention of HIV acquisition shows considerable promise (Gray et al., 2012). Pre-exposure antiretroviral prophylaxis lowers the risk of infection, particularly if adherence to treatment is high (Okwundu et al., 2012). Treatment of an HIV-infected individual with ART benefits that person and substantially reduces the likelihood of transmitting HIV to his or her uninfected sexual partner (Cohen et al., 2011); additionally, it can significantly reduce community-level HIV incidence (Granich et al., 2013). Research into the social and behavioral factors governing acceptance and uptake of these interventions will guide effective deployment. Thus, for the first time since AIDS was recognized, the goal to control and even end the HIV/AIDS pandemic has become part of the global health dialog (Folkers and Fauci, 2010). Despite these accomplishments, there is much unfinished business. While expanding availability of existing interventions, new prevention and treatment methods must be developed. An HIV vaccine is a crucial goal for prevention, and several strategies are being pursued. Although an effective vaccine has proven elusive so far, a trial (RV144) undertaken in Thailand showed a modest 31% reduction in infection in people given the vaccine (Rerks-Ngarm et al., 2009). Traditionally, induction of neutralizing antibodies against the targeted pathogen is the hallmark of a successful vaccine. So far, HIV vaccines, including the RV144 candidate, have been unable to generate broadly neutralizing antibodies or cytotoxic T cell responses capable of preventing HIV infection in human trials. In fact, natural infection with HIV elicits detectable broadly neutralizing antibodies in about 20% of infected individuals—a process that takes 2 years or longer. On the basis of this finding, several groups of investigators have pursued an alternative B cell vaccine strategy: broadly neutralizing antibodies derived from infected individuals have been used to identify epitopes on the HIV envelope trimer that could be used as immunogens to induce broadly reactive antibodies (Klein et al., 2013; Hoot et al., 2013; Kwong et al., 2013). This B cell pathway toward an HIV vaccine will likely need to be combined with an additional strategy involving the induc-