Virus-specific CD4 T-cell helper response, known to have a key role in maintaining a protective cytotoxic T lymphocyte (CTL) response in chronic viral infections, 1 are not usually detected in HIV-1 infected people even in early stages. 2 Consequently, this response may play an important part in the control of HIV-1 disease. HIV-1-specific CD4 T-cell proliferative response is associated with control of viraemia in a few untreated long-term non-progressors as well as in acutely infected people whose viraemia is reduced by highly active antiretroviral therapy (HAART) started before seroconversion. 1 By contrast, this response is absent in patients with long-standing HIV-1 infection receiving HAART. 3

We examined the effect of HAART started in the early stages of HIV-1 infection on the HIV-1-specific proliferative response, to determine if the inhibition of viral replication early in the course of infection allowed generation of this response. 159 HIV-1 infected people without symptoms and with CD4 T-cell counts above 500106/L and a baseline plasma viral load above 10 000 copies/mL were randomised to receive no therapy or treatment with zidovudine (ZDV)+ zalcitabine (ddC), ZDV+ didanosine (ddI), stavudine (d4T)+ ddI, or d4T+ lamivudine (3TC)+ ritonavir as part of the Spanish EARTH-1 study. The lymphocyte proliferative response to a polyclonal stimulus, pokeweed mitogen (PWM), to recall antigens, tetanus toxoid, a ubiquitous antigen cytomegalovirus (CMV), 4, 5 and to HIV-1 recombinant proteins gp160, p24, and gp120, was examined in all the people recruited at our institution (13 untreated and 26 treated for 1 year; 18 with double and eight on triple therapy). In addition, eight HIV-1-negative healthy people were