More than a quarter century of AIDS later, where do we stand against this disease? A couple of advances amongst many warrant measured optimism. First, we have made remarkable strides in developing antiviral drugs or antiretrovirals (ARVs). Since 1996, ARVs have saved an estimated 3 million life-years in the United States alone. An upside to this therapeutic advance is that currently more than 2 million HIV-positive people are being treated with ARVs. While drug resistant viruses continue to be a significant issue , this past year saw the emergence of a new class of drugs targeted against the HIV-1 integrase enzyme . Different from inhibitors that target the reverse transcriptase and protease enzymes and drugs that affect viral entry into the cell, this new integrase inhibitor will prevent the viral DNA from inserting itself into the host cell genome. A downside to treatment remains that still less than 20% of the world's population has access to HIV drugs and prevention programs, and that for every one person who gains therapy, six others become newly HIV-infected without the prospect of future treatment. Ongoing investments from the United States President's Emergency Plan for AIDS Relief , the Global Fund to Fight AIDS, Tuberculosis and Malaria, and many other programs are making steady progress in attempting to turn the tide on worldwide treatment access. Second, a welcome development is the recent documentation that circumcision reduces by approximately 50% a man's risk of acquiring AIDS sexually. This piece of good news suggests that there is still much to be gained through public health prevention measures. Independent of drug therapy, education, condoms, circumcision, abstinence, and other intervention strategies may yield significant and yet unharvested global benefits.
There have also been two notable recent disappointments. The first is the serious setback of the failed clinical vaccine trial from the collaborative efforts of Merck & Co., Inc., the US National Institute of Allergy and Infectious Diseases (NIAID), and the HIV Vaccine Trials Network (HVTN). In this sizable clinical trial, 49 of 914 vaccinated men tested positive for HIV, compared to 33 of 922 men who received a placebo vaccine . These results illustrate a disappointing lack of vaccine efficacy and dash the hope that a useful HIV-vaccine will be available any time soon. As the Merck vaccine was based on the induction of cellular immunity by HIV proteins expressed from an adenoviral vector, we will likely see a return to attempts to modify the viral envelope protein in such a way to induce neutralizing antibodies. This seems a formidable task that requires innovative approaches, as all the standard ways to make such an envelope immunogen have failed. A second less visible but perhaps equally troubling concern is our continued inability to develop a safe and effective anti-HIV microbicide for women . In sub-Saharan Africa, women between the ages of 15–24 are three times more likely than men to become infected with HIV. Our failure to empower women to protect them against HIV/AIDS poses a sobering challenge.