The Next Frontier

Welcome to our third issue of HIV Plus. In the nine months since we made our debut, so much progress has been made in the field of HIV that many scientists consider today to be one of the most exciting times in HIV research. Others regard the current reality as more surreal. For many people living with the virus here and in the developing world who are failing to benefit from the newest regimens, the gap between promising treatments and the desperation they feel about their own survival is stark.

I think it's important to remember that any progress we make in science or medicine is ultimately measured in human and quality-of-life terms and here, the global scorecard is decidedly negative. The latest reports show that HIV is continuing to spread and mutate across the world, and we are providing little help for the millions living in the epicenter of the epidemic, namely sub-Saharan Africa and southeast Asia. We have made some inroads towards an HIV vaccine, but we aren't there yet.

Meanwhile, the very high cost of anti-HIV drugs remains a significant obstacle here in the U.S. as well. The issue is hardly new: activists took the streets in the mid-80's to protest the high price of AZT and haven't stopped fighting for fair prices. As Stanya Kahn reports, the ongoing crisis in AIDS funding underscores our urgent collective need for a more innovative, long-term approach to paying for HIV care (see "The Other War On Drugs").

On the research front, though, we have indeed entered a new era, one that can be summed up in a single word: latency. Today, we have a battery of powerful antiretroviral drugs that can effectively stop active HIV infection in many people. The drugs are no picnic: they can be toxic and cause side effects. They are also hard to take for many people, especially since skipping doses leads to drug resistance. But these problems are being tackled with more powerful drugs and simpler regimens. For now, in many people, we have the means to control 99 percent of HIV infection, using a "hit early-hit hard" chemotherapy approach modeled after cancer therapy.

What remains leftover is a reservoir of dormant or "latent" HIV virus hidden in lymphoid tissue and sanctuary sites like the brain that appear hard to treat with current drugs (see Updates). New studies show that these latent HIV reservoirs are established in the first days of exposure to the virus. This discovery has changed our view of the disease and altered our approach to long-term treatment. For now, it's unclear whether we'll really be able to eradicate every last speck of HIV lurking in the body, yet that may not be necessary. Instead, the immune system, with some help, may be capable of controlling latent HIV infection.

At a recent meeting of AIDS researchers in Chicago, there were promising reports regarding a variety of new strategies to boost the immune system in people taking HIV therapy. One of them included the controversial idea of "drug holidays." As of early January, several individuals with undetectable viral infections who interrupted and then eventually quit their drug therapy, now have undetectable or very low-level HIV infections. They are latently infected, say scientists, but remain healthy. Like a vaccine, repeated exposure to the virus appeared to have boosted HIV-specific immune responses needed to control any emerging virus. For now, we don't know if or how long this will last, but it's another important step.

Other exciting clues come from an unexpected source: African sex workers. For over 15 years, groups of prostitutes in Kenya and Gambia have remained HIV-negative and healthy despite years of repeated exposure to the virus. Some of these women appear to be genetically resistant to the virus, and, as we report here, so do their relatives (see "Designer Genes").

In this issue, we've also focused on other sexually-transmitted diseases like herpes that serve as models for the prevention and treatment of latent infections. STDs are important co-factors that can increase the risk of HIV transmission (see "HIV's Hidden Partner"). As we step into the new era of HIV latency, STDs should also move to the top of our list as an integrated part of HIV care. I'll see you on the frontlines.

ANNE-CHRISTINE D'ADESKY
EDITOR IN CHIEF