In the past decade, HIV infection in the industrial world has largely evolved from a virtual death sentence to more of a chronic disease, which is a testament to the efforts of researchers and patient advocates. But the 40 million HIV-positive people worldwide are a somber reminder of the work ahead. Resistant strains of the virus have appeared; citizens in developing countries lack access to lifesaving drugs; and basic questions about the progression of the virus postinfection remain. Yet 2005 brought hopeful news on all fronts.
Researchers know that HIV infection leads to a massive depletion of CD4 white blood cells, but why this happens is still up for debate. Is the virus killing all the cells directly, or is there an indirect mechanism that explains the widespread death? Daniel C. Douek, an immunologist in the Vaccine Research Center at the National Institutes of Health, implicates both direct and indirect mechanisms. His work shows that HIV starts in the gut, home to the largest population of the virus's preferred CD4 targets—those with a receptor called CCR5. HIV attacks and kills these cells directly early in the course of the infection.
The mechanism behind CD4 cell death turns indirect as the disease continues. The lack of immunity in the gut allows other pathogens to thrive. This condition overstimulates the lymph nodes, and they activate large numbers of CD4 cells. Once activated, the cells progress through a natural process that eventually leads to their death, whether or not they are infected. Continuous rounds of activation and death slowly deplete CD4s. Douek's research not only sheds light on how HIV wreaks havoc, it also suggests that HIV vaccines might do well to initiate an immune response in the gut.
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With vaccines still on the horizon and with HIV strains developing resistance to antiretrovirals, identifying new drugs is critical. Current treatments focus on disrupting viral proteins, which have many opportunities to mutate. But HIV also relies on various host cell proteins, so researchers are beginning to investigate as therapeutic targets these human proteins, which are much less likely to mutate.
Joachim Hauber of the Heinrich Pette Institute in Hamburg, Germany, has discovered one such target: deoxyhypusine synthase (DHS), an enzyme that activates a host protein necessary for viral replication. Hauber's group found it could inhibit the virus by blocking DHS with an experimental drug. The drug did not appear to harm host cells or induce resistance after prolonged use and was effective against strains resistant to current antiretroviral therapies. Even though potential treatments are still years away, Hauber's work demonstrates a powerful new offensive strategy.
Today's drugs have made HIV infection a manageable disease for many, but millions in developing countries cannot afford them. A South African advocacy group founded in 1998, Treatment Action Campaign (TAC), has worked toward greater access to HIV therapies for the estimated 5.3 million infected in their country. TAC's legal actions have forced the government to provide free antiretrovirals to HIV-positive pregnant women. More recently, TAC has negotiated a discount from Bristol-Myers Squibb on amphotericin B, used to treat a deadly opportunistic infection common to HIV patients. And this past February, TAC launched a campaign urging the government to treat 200,000 people with no-cost antiretrovirals by 2006. TAC chairman Zackie Achmat has said that the government must wake up to AIDS; TAC is ringing the alarm.