People with HIV whose virus is resistant to four classes of antiretroviral drugs have a higher rate of serious illness and death. Extensive drug resistance is most common among long-term survivors. Researchers analyzed data from 148 people with HIV in Italy who had documented viral resistance to nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and integrase inhibitors. In this group, 38 people experienced a new major health event, including 18 AIDS-defining events, 32 non-AIDS events and 12 deaths, for a combined rate of 9.12 events per 100 cumulative years of follow-up. Six percent died within four years. People who experienced either AIDS-defining or non-AIDS health events had a nearly threefold higher risk of death. The study authors concluded that people with highly resistant HIV “have a high burden of disease with a worrying incidence of malignancies” and urged doctors caring for this population to provide close monitoring and access to innovative therapies.