Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death.

Background: A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown.

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy.

Background: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain.

Methods: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.

Treatment initiation with zidovudine-containing potent antiretroviral therapy impairs CD4 cell count recovery but not clinical efficacy.

Objective: Zidovudine-containing antiretroviral therapy has been associated with a lower rise in absolute CD4 cell counts in several randomized trials. We examined the predictive factors for this phenomenon and assessed its impact on clinical progression during treatment in a large patient cohort.

Design: An analysis of data from the Swiss HIV Cohort Study.

Immunological recovery and antiretroviral therapy in HIV-1 infection.

Potent antiretroviral therapy has dramatically improved the prognosis of patients infected with HIV-1. Primary and secondary prophylaxis against Pneumocystis carinii, Mycobacterium avium, cytomegalovirus, and other pathogens can be discontinued safely once CD4 cell counts have increased beyond pathogen-specific thresholds. Approximately one-third of individuals receiving antiretroviral therapy will not reach CD4 cell counts above 500 cells per muL after 5 years despite continuous suppression of plasma HIV-1 RNA.

Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy.

Background: The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)-infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration.

Methods: Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load <1000 copies/mL for > or =5 years.

Productivity costs and determinants of productivity in HIV-infected patients.

Background: In HIV-infected patients, reduced ability to work may be an important component of the societal costs of this disease. Few data about productivity costs in HIV-infected patients are available.

Objective: The goals of this study were to estimate productivity costs in the HIV-infected population in Switzerland and to identify characteristics that may influence patient productivity.

Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes.

CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis. Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and Fas were determined in 55 HIV-1 infected persons treated with highly active antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA remained elevated.

Long-term virological response to multiple sequential regimens of highly active antiretroviral therapy for HIV infection.

Objective: Information about the virological response to sequential highly active antiretroviral therapy (HAART) for HIV infection is limited. The virological response to four consecutive therapies was evaluated in the Swiss HIV Cohort.

Design: Retrospective analysis in an observational cohort.

Naive T cells are maintained by thymic output in early ages but by proliferation without phenotypic change after age twenty.

Analysing T-cell receptor excision circle numbers in healthy individuals we find a marked change in the source of naive T cells before and after 20 years of age. The bulk of the naive T cell pool is sustained primarily from thymic output for individuals younger than 20 years of age whereas proliferation within the naive phenotype is dominant for older individuals. Over 90% of phenotypically naive T cells in middle age are not of direct thymic origin.

CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study.

Background: Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-1 infection allows recovery of CD4 T lymphocytes. Few studies have explored the long-term T-lymphocyte responses to HAART.

Methods: Plasma HIV-1 RNA levels and CD4 and CD8 T-lymphocyte counts were longitudinally analyzed over 4 years in 2235 participants of the Swiss HIV Cohort, commencing HAART between 1996 and 1997.

Greater reversal of CD4+ cell abnormalities and viral load reduction after initiation of antiretroviral therapy with zidovudine, lamivudine, and nelfinavir before complete HIV type 1 seroconversion.

In a prospective open-label study, 41 male subjects received nelfinavir, zidovudine, and lamivudine stratified as either: early stage (ES; negative/indeterminate Western blot; n = 19) or late stage (LS; positive Western blot; n = 22) primary HIV-1 infection. Despite higher median baseline HIV-1 RNA levels and lower CD4(+) cell numbers in the ES subjects, a significantly greater decline in viral load (-3.46 vs.

Dynamics of T cells and TCR excision circles differ after treatment of acute and chronic HIV infection.

We quantified T cell proliferation and thymic function in primary HIV infection (PHI; n = 19) and chronic HIV infection (CHI; n = 14) by measuring Ki67 staining and TCR excision circle (TREC) number. After antiretroviral therapy of PHI there is a profound decrease in the number and percentage of Ki67(+) T cells (<6% Ki67(+)) with no significant increase in TREC per million cells and a transient increase in TREC per milliliter. In contrast, after antiretroviral therapy of CHI there is a reduction in the percentage but little change in the total number of Ki67(+)CD4(+) T cells associated with increases in both TREC per million cells and TREC per milliliter.

Potential benefit and limitations of a broad access to potent antiretroviral therapy in developing countries.

In industrialised countries, highly active antiretroviral therapy (HAART) has drastically reduced HIV mortality. Only few developing countries have introduced HAART on a large scale, leaving millions of HIV-infected individuals without life-saving therapy. Although HAART appears to be economically viable for middle income countries, it remains unaffordable for many of the poorest and worst affected nations.

The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T lymphocyte response to potent antiretroviral therapy.

Objective: To study the long-term immunological recovery in HIV-1-infected individuals receiving potent antiretroviral therapy (ART).

Design: Prospective, observational study.

Methods: Plasma HIV-1 RNA, CD4 and CD8 T lymphocyte counts were determined at 3-6 monthly intervals in 95 HIV-1-infected subjects receiving ART who suppressed plasma HIV-1 RNA to levels below 400 copies/ml during a median observation period of 45 months.