Redefining Failure and Success
There's been recent talk of a third era of HIV treatment - one that incorporates current insights about what highly active antiretroviral therapy (HAART) can do, with an ever-expanding knowledge of its limitations. New evidence sugests that lowering viral load may dramatically reduce the risk of heterosexual transmission. A study of 415 Ugandan couples in which one partner had the virus and the other did not found that having a viral load of less than 1,500 copies all but eliminated the risk of passing on HIV. This was true for men and women. Study participants did not receive any antiretroviral medication, so the results suggest that low viral loads were the result of good immune control. It remains to be seen whether lowering viral load with drugs will offer the same protection.

As for the anti-HIV drug pipeline, T-20 and T-1249 (Trimeris) are fusion inhibitors that continue to look promising; now more accessible, Abbott's lopinavir (ABT-378) is still speeding along the path to approval; treatment activists warn that the new potent protease inhibitor may be pricier than most. Meanwhile, Bristol-Myers Squibb is due to release a reformulated, enteric-coated formulation of its drug Videx, or ddI. It will allow for simpler dosing-and may also come with a hefty price increase. On a more sobering note, lodenosine (F-ddA), a nucleoside analog manufactured by U.S. Bioscience, was recently pulled from development after being linked to the deaths of four trial participants. To date, only Sustiva has received traditional approval from the Food and Drug Administration; all the other anti-HIV drugs were given accelerated approval based on other criteria.

A note of warning has also crept into discussions of current approaches to treatment. Although HAART continues to effectively bring down viral load and boost T-cells, it can't resolve - and may exacerbate - pre-existing conditions like hepatitis, pancreatitis, and coronary heart disease. The bottom line: viral load and T-cell counts may not be enough to predict survival and long-term health.

Other drug-related side effects, like loss of bone density (avascular necrosis), have raised questions about unforseen consequences of a life time spent on HAART. German researchers have identified another deficiency-this time with sulfur-that occurs in HIV-positive people on and off drug therapy. What's actually missing is glutathione, a form of sulfur that helps fuel cell activities. Since the late 1980s, treatment advocates have tracked glutathione deficiency and studied the possibility of treating it with a range of nutritional supplements, including N-acetyl cysteine (NAC). The German finding may spur new investigations into nutritional deficiences caused by HAART and HIV. Long-term studies are needed to fill in many of the missing pieces, along with a closer look at management of slower-moving conditions, like some cancers. The latest word is that all HIV-positive men should consider routine anal Pap smears to screen for anal cancer, just as women should get Pap smears to detect cervical cancer.

The chart below specifies the main features of each drug. For a more complete list and updates, check with your doctor or community health organization.

- EB, ACD