The Washington Blade, January 7, 2000

Once again, a group of researchers has emerged with some evidence to argue that early intervention with a triple-drug therapy can have "a major effect on the outcome of HIV infection" and "provide[s] the highest chance of normalization" of the immune system.

The latest to weigh in is a team led by renowned Italian researcher Franco Lori, working at the Research Institute for Genetic and Human Therapy in Washington, D.C. Lori's team gave 10 patients hydroxyurea-ddi-indinavir before their immune systems had begun developing antibodies.

Hydroxyurea (a cancer drug) and ddi (a nucleoside analog) have demonstrated strong ability against the AIDS virus in immune cells where the virus tends to lie dormant. Indinavir (a protease inhibitor) has demonstrated effectiveness against the virus in cells that are actively replicating. Thus, Lori's group wanted to see whether the three drugs together could have any significant effect on preserving the immune system if given so soon after initial infection that the immune system has yet to develop HIV antibodies.

The team concluded that such a combination given at such a time "leads to normalization of immunologic defects" caused by HIV infection and that it "limits the establishment of HIV reservoirs." As with other triple-drug combinations, the patients taking hydroxyruea-ddi-indinavir saw their viral loads drop dramatically, below 50 viral particles per milliliter. But the 10 taking the combination before they had developed antibodies also experienced a much slower progression to that point of testing positive (one patient took more than a year, versus the usual two to six weeks). Most of the 10 also had "vigorous" CD4 immune responses and only the most sophisticated of tests could detect any replication-competent virus in the patients. In one patient, no replication-competent virus could be found.

"Although these results confirm recent studies that early treatment does not prevent the establishment of latent cellular reservoirs for HIV," wrote the researchers in the December issue of the Journal of Infectious Diseases, "our data show that treatment before seroconversion with hydroxyurea, didanosine, and indinavir is associated with an unusually low frequency of latently infected cells." "Our findings provide evidence that the earliest treatment leads to the fastest recovery of the naive cell repertoire," concluded the team. "Furthermore, early treatment might be the only chance to limit the establishment and expansion of latent HIV reservoirs." "[A]lthough recovery of immune functions and normalization of some immune parameters have been demonstrated when treatment is initiated during chronic HIV infection," noted the doctors, "recovery was incomplete and did not occur in all patients. Our data suggest that the time before complete seroconversion might provide an important window for therapeutic intervention to prevent irreversible immune damage. Limiting the number of resting infected cells very early after infection might also have implications in the control of HIV replication." The combination of hydroxyurea-ddi-indinavir was the same used by the so-called "Berlin patient," who has been able to keep his viral load down for more than two years after having gone off that combination twice. The patient had taken the hydroxyurea-ddi-indinavir before his body had begun developing antibodies to the AIDS virus, and experts have speculated that going on and off the combination might have "taught" his immune system how to fight HIV on its own. Lori's team's research seems to suggest that the Berlin patient's success might also be due to his initiating therapy before his body began producing HIV antibodies.

In brief ...

RITONAVIR WORRY: The use of the protease inhibitor ritanovir (Norvir, by Abbott) appears to increase the chances for severe liver problems, according to a study out this week from Johns Hopkins University. The study, in the Jan. 5 issue of the Journal of the American Medical Association, notes that doctors followed 298 patients taking either a three-drug protease inhibitor combination or a two-drug nucleoside combination. About half had co-infection with hepatitis B and hepatitis C. While some increase in liver toxicity was associated with each combination, those using ritonavir accounted for five times the number of cases the others did.

HOME TEST CONCERN: The U.S. Federal Trade Commission last month charged a firm doing business on the Internet with "falsely representing that his HIV tests accurately detected HIV." According to the FTC, the company, Medimax Inc., was selling tests that "provided false negative results" nine times out of 10, and that "the 10th test did not work at all." In November, the FTC settled a similar complaint with another Internet marking company, Cyberlinx. The company agreed to stop marketing any HIV test kits and to pay back the money it received from the sale of tests previously sold.

D.C. CLINICAL TRIALS: The National Cancer Institute's HIV and AIDS Malignancy Branch (HAMB) is enrolling volunteers for a variety of HIV-related trials. The new 800-number to call for information is 800-243-2732, then choose No. 4. To check for trials on the Web, use www-dcs.nci.nih.gov/aidstrials.