Anti-HIV Drugs
Non-protease drugs-gain ground.

One new drug has been added to the arsenal of approved anti-HIV agents, while another new agent is being widely used on an experimental basis as "salvage therapy," increasing the dizzying number of potential drug combinations in use today. Today, 17 anti-HIV drugs are being used in combination regimens, including three through expanded-access programs (indicated with an asterisk* below). Other classes of drugs attack different HIV enzymes that are involved in viral reproduction. Protease inhibitors, for example, block the protease enzyme.

Following solid reports at the 12th World AIDS Conference in Geneva, the Food and Drug Administration speedily approved Sustiva (efavirenz), a non-nucleoside reverse transcriptase inhibitor (or "non-nuke") manufactured by DuPont. Sustiva's approval marks the coming-of-age of effective anti-HIV drugs that work differently from protease inhibitors and are being combined with older AZT-like nucleoside-analog drugs. Based on several clinical trials, Sustiva is now recommended for first-line treatment of HIV infection in combination with other drugs. On November 2, an FDA advisory panel recommended that the agency approve Ziagen (Glaxo Wellcome), a nucleoside analog drug now available through expanded access. Full approval is pending.

Glaxo Wellcome's protease inhibitor, Agenerase (amprenavir), formerly known as 141W94, has also been added to the list of drugs available through expanded access; it's obtainable by people who have taken at least one protease inhibitor in the past. Clinical trials of Agenerase are looking at the drug's effect on lipid metabolism and lipodystrophy, a fat disorder that occurs with many HIV drugs.

New side effects and toxicities are also emerging. People taking Gilead's Preveon (adefovir dipivoxil), a powerful nucleotide analog reverse transcriptase inhibitor should watch for kidney toxicity linked to an accumulation of the drug in the blood. Gilead recommends that people reduce their dose of Preveon after 16 to 20 weeks and monitor serum creatinine levels (a measure of kidney function).

The emergence of other HIV-drug related side effects, such as lipodystrophy, has prompted advocates to call for the creation of large databases that would allow people on therapy and their caretakers to directly input and access information about their treatment experiences as well as get updates about drug resistance and side effects.

To counter long-term drug toxicity, drug companies are trying to simplify drug regimens and reduce drug doses while maintaining their effectiveness. A recent study of Viracept (nelfinavir), for example, shows that a twice-daily 1250-milligram dose works as well as the thrice-daily 750-milligram dose. But the jury's still out on other drugs. Although preliminary data supported twice-daily dosing of Merck's protease inhibitor Crixivan (indinavir), in September, Merck issued an emergency warning to physicians and patients warning them to continue or switch back to thrice-daily dosing.

Manufacturers are also grappling with problems in drug formulations. A new study shows that the pediatric formulation of Videx (ddI) may be just as effective and much easier to take than the buffered adult form, which frequently causes diarrhea. A separate problem faces those taking Norvir. In late July, Abbott officials announced an indefinite stop to the production of Norvir capsules due to an absorption problem (see "Norvir Alert".)

Meanwhile, positive, albeit mixed, reports continue to trickle in about hydroxyurea (Bristol-Myers Squibb), an anticancer drug that works well with ddI and appears to be active against latent HIV. Other promising agents include fusion, zinc finger and integrase inhibitors. In a recent phase I/II study of T-20, a fusion inhibitor, the drug reduced the level of HIV in patients' blood by 99 percent.

The selective table below is designed to note the main features of each drug. Remember: HIV can develop resistance to all HIV drugs, so it's important to choose your initial regimen carefully. Read the drug package insert and consult your doctor or AIDS treatment groups for updates.

Other Drugs