CD4 T-Lymphocyte Recovery in Individuals With Advanced HIV-1 Infection Receiving Potent Antiretroviral Therapy for 4 YearsThe Swiss HIV Cohort Study

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Abstract
HIGHLY ACTIVE antiretroviral therapy (HAART) has significantly improved the prognosis of individuals infected with human immunodeficiency virus (HIV)-1 and extended life expectancy.1-5 The recovery of CD4 T lymphocytes in treated persons is usually accompanied by enhanced T-lymphocyte responses to antigens and mitogens,6-8 providing adequate protection against opportunistic infections.3,9-11 However, the immunological recovery shows a large variability from patient to patient.12-16 A significant proportion of treated subjects experience only small increases in CD4 T-lymphocyte numbers despite optimum suppression of plasma HIV-1 viremia by HAART. In others, CD4 T-lymphocyte count rapidly rises despite modest reductions of plasma HIV-1 RNA levels.17 The reasons for these different responses remain unknown. It has been suggested that differences in residual thymic function may play a role,18 but additional factors may potentially affect the recovery of CD4 T lymphocytes, including age,19 the degree of immunodeficiency before initiation of HAART,20 residual viral activity,21 viral coinfections such as hepatitis C or G,22-24 and the susceptibility of CD4 T cells to HIV-1 infection, which depends in part on the expression of the viral coreceptor CCR5.25-27