Doctors prescribing protease inhibitors to patients with AIDS should monitor liver enzyme levels for signs of toxicity. In particular, ritonavir should be used with caution in patients with underlying liver disease. These are the conclusions of a study conducted by Professor Mark Sulkowski (assistant professor of medicine, Johns Hopkins university, US) and colleagues in the Journal of the American Medical Association (2000;283:74).
They analysed 211 people being treated with the protease inhibitors ritonavir, saquinavir, indinavir and nelfinavir over a two-year period. Of these patients, 10 per cent experienced liver toxicity at a level high enough to warrant stopping the treatment. The researchers also found that the risk of liver toxicity was increased five-fold with ritonavir, which accounted for half the cases in the study. They speculate that this may be linked to the fact that ritonavir is a potent inhibitor of the cytochrome P450 system.
"Based on anecdotal reports, there had been a feeling that all protease inhibitors were equally toxic to the liver and that is not what we found," says Professor Sulkowski.
The authors comment that some doctors have been reluctant to prescribe protease inhibitors and have chosen other drugs that have turned out to be either harder to take or less effective. They conclude that, while liver toxicity is fairly high with protease inhibitors, they can be used safely if liver enzymes are monitored closely.
Abbott Laboratories, the manufacturer of ritonavir (Norvir) in the UK had no comment to make at this stage on the findings of the study.
Data from a study reported in Nature Medicine (2000;6:71) suggest that there is a difference between men and women in the way that they are infected by HIV-1.
Dr Julie Overbaugh (Fred Hutchinson Cancer Research Centre, Seattle, US) and colleagues compared men and women from Kenya who had become infected with HIV-1 through heterosexual contact. They found that the women were often infected by multiple virus variants early after infection, whereas the men were not. This contrasted with results from American and European studies of predominantly male cohorts that showed an homogenous virus population.
They say that women appear to be infected by multiple viruses from their partners, whereas most men are productively infected by only a single viral genotype. The authors say that extrapolating trial results obtained from predominantly male populations to women should be done with caution. Women now comprise almost half of new HIV-1 infections worldwide, they say.
A new approach has been used to prove that there is ongoing HIV-1 replication in a large percentage of infected individuals on highly active antiretroviral therapy (HAART). Dr Mark E. Sharkey (University of Massachusetts medical school, US) and colleagues (Nature Medicine 2000;6:76) say they have detected viral episomes using a new technique. Episomes are particles of viral DNA; their presence indicates that replication is occurring. Professor Sharkey et al say that their discovery that viral replication occurs even in patients with undetectable levels of plasma viral RNA will have significant implications for the management of patients and for the development of virus eradication strategies (see also PJ 1999;263:738).