Drug resistance vexes treatment of AIDS.

Two reports in the April 22 NEW ENGLAND JOURNAL OF MEDICINE highlight the complexities and pitfalls of treating people with AIDS. One study finds that AIDS patients can become infected with a more lethal form of the tuberculosis bacterium while recovering from an earlier bout with TB. The second discusses the novel case of a patient who, before treatment, harbored a strain of AIDS virus resistant to zidovudine (AZT), one of the few effective AIDS drugs. Conventional wisdom holds that a single infection confers immunity to the virulent Mycobacteriurn tuberculosis, which causes TB. But using a technique called DNA fingerprinting to identify different strains of the TB bacterium, researchers led by Peter M. Small, a Howard Hughes Medical Institute investigator at Stanford University, have now demonstrated that four TB patients became infected with a new, multidrug-resistant form of the disease while undergoing treatment for a previously diagnosed infection. All four men had AIDS, the advanced stage of HIV infection that cripples the immune system. All four died from the second TB infection after almost recovering from the first.

"I think that's very bad news," comments David E. Rogers of Cornell University Medical College in New York City Until now, research had not clearly documented TB "superinfection" in people with AIDS, although many of us have been concerned that it might happen; says Rogers, vice chair of the National Commission on AIDS.

Investigators have documented numerous outbreaks of multidrug-resistant tuberculosis in the past few years (SN: 2/6/93, p.90). Up to 90 percent of people with AIDS who get multidrug-resistant TB may die of TB, notes Small. In people treated for multidrug-resistant TB who do not have AIDS, the death rate falls to 40 to 50 percent.

Typically, drug-resistant strains of M. tuberculosis arise because of inadequate or incomplete drug therapy This partial dosing kills the weakest bacteria first, allowing drug-resistant strains to proliferate. Public health officials should now consider reinfection a third possible explanation for the emergence of drug-resistant TB, says Small. But most instructive, the study "emphasizes the importance of conventional tuberculosis control, which is to identify sick patients and get them on therapy as soon as possible," he explains.

Moreover, because AIDS patients may die before they can be treated effectively for multidrug-resistant TB, public health officials should place "more emphasis on prevention of exposure," Small says. "As tuberculosis becomes multidrug-resistant, it essentially becomes untreatable." he warns. "And the only appropriate response to untreatable diseases is prevention."

In the second report, Alejo Erice of the University of Minnesota Medical School in Minneapolis and colleagues discuss the case of a 20-year-old man infected with a strain of HIV that proved resistant to AZT. Typically, the AIDS virus loses its sensitivity to the drug alter six to 12 months of treatment, the researchers note.

In this case, however, the patient had sexual contact with an HIV-positive partner already on AZT, from whom he presumably contracted a drug-resistant strain of the virus, say the researchers. Physicians started the newly infected patient on AZT, but his health failed to improve and his HIV infection grew even more resistant to AZT. Eventually, physicians switched him to didanosine, another antiviral agent.

The researchers deem it "likely" that some of the estimated 40,000 new cases of HIV infection each year will prove resistant to AZT from the outset. Consequently, the researchers recommend that any future clinical trials to test the benefits of treatment with AZT and other antiviral drugs include tests for drug resistance.