Hit HIV-1 hard, but only when necessary

Randomised, controlled trial data show that combination antiretroviral ther apy for HIV-1 infection benefits people with CD4-cell counts less than 350 cells/mu L. Based on currently known risks and benefits, we believe that if CD4-cell counts and viral load are monitored carefully, and highly active antiretroviral therapy (HAART) is started commonly when the CD4-cell count drops below 350 cells/mu L, then clinically relevant immune-system damage a nd progression to AIDS and death can be greatly delayed or prevented. This approach is dictated by three features of HIV-1 infection that are not typi cal of infectious diseases: no available regimen can eradicate HIV-1; all c urrently effective regimens may cause undesirable, sometimes life-threateni ng, toxic effects; and, unless regimens are strictly adhered to, multidrug resistance can develop, limiting future treatment options. If therapy is st arted too early, cumulative side-effects of the drugs used and the developm ent of multidrug resistance may outweigh the net benefits of the lengthenin g of life. If therapy is started too late, increases in disease progression and mortality outweigh the risk of adverse events. A patients' activist (M H) and a clinician (CCJC) discuss data that justify this balanced approach and the feasibility of randomised controlled trials to provide clearer answ ers about when to start treatment.