Contribution of Low CD4 Cell Counts and High Human Immunodeficiency Virus (HIV) Viral Load to the Efficacy of Preferred First-Line Antiretroviral Regimens for Treating HIV Infection: A Systematic Review and Meta-Analysis.

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or >200 CD4/µL) or VL (≤ or >100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 <200 cells/µL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.

Balance between activation and regulation of HIV-specific CD8+ T-cell response after modified vaccinia Ankara B therapeutic vaccination.

BACKGROUND: The causes of HIV-vaccines failure are poorly understood. Therapeutic vaccination with modified vaccinia Ankara (MVA)-B in HIV-1-infected individuals did not control the virus upon analytical treatment interruption (ATI). We investigated whether the functional characteristics of HIV-specific CD8 T-cell responses stimulated by this vaccine, and the level of exhaustion of these cells might explain these results. METHODS: Twenty-one HIV-1 chronically infected patients on combination antiretroviral therapy, included in the therapeutic vaccine trial RISVAC03, were studied: 13 immunized and eight controls. Functional characteristics, cytotoxic potential and exhaustion of HIV-specific CD8 T cells, were evaluated by polychromatic flow cytometry. Differences between groups were tested using nonparametric tests. RESULTS: MVA-B vaccine induced an increase in HIV-specific CD8 T-cell response, but also increased their levels of exhaustion. At week 18 (following three immunizations) the level of response increased with respect to baseline (P = 0.02). A significant increase at weeks 18 and 24 (ATI) in granzyme B content was also observed. Interestingly, an increase in expression of exhaustion markers was found at weeks 18 (P = 0.006) and 24 (P = 0.01). However, there was no significant change in the functional profile of vaccine-induced CD8 cells. At week 36, in parallel to the rebound of plasma viremia after 12 weeks ATI, a significant increase in the level of CD8 response, in granzyme B content and in exhaustion markers expression, was observed in both groups. CONCLUSION: We show that therapeutic vaccination with MVA-B tilts the balance between activation and regulation of the response of HIV-specific CD8 T cells towards regulation, which impacts on the viral rebound after ATI.

Prevention of opportunistic infections in adult and adolescent patients with HIV infection. GESIDA/National AIDS Plan guidelines, 2004 [correction].

OBJECTIVE: To provide an update of guidelines from the Spanish AIDS Study Group (GESIDA) and the National AIDS Plan (PNS) committee on the prevention of opportunistic infections in adult and adolescent HIV-infected patients. METHODS: These consensus recommendations have been produced by a group of experts from GESIDA and/or the PNS after reviewing the earlier document and the scientific advances in this field in the last years. The system used by the Infectious Diseases Society of America and the United States Public Health Service has been used to classify the strength and quality of the data. RESULTS: This document provides a detailed review of the measures for the prevention of infections caused by viruses, bacteria, fungi and parasites in the context of HIV infection. Recommendations are given for preventing exposure and for primary and secondary prophylaxis for each group of pathogens. In addition, criteria are established for the withdrawal of prophylaxis in patients who respond well to highly active antiretroviral therapy (HAART). CONCLUSIONS: HAART is the best strategy for the prevention of opportunistic infections in HIV-positive patients. Nevertheless, prophylaxis is still necessary in countries with limited economic resources, in highly immunodepressed patients until HAART achieves beneficial effects, in patients who refuse to take or who cannot take HAART, in those in whom HAART is not effective, and in the small group of infected patients with inadequate recovery of CD4+ T lymphocyte counts despite good inhibition of HIV replication.

Differential characteristics of HIV-infected penitentiary patients and HIV-infected community patients.

PURPOSE: To identify particular characteristics of HIV+ patients from correctional facilities (CF) compared with an HIV+ population from the community to better detect variables for intervention. METHOD: In our hospital, HIV+ patients are admitted to an infectious diseases ward (IDW) when they come from the community or to a penitentiary unit (PU) when they are transferred from CF. We retrospectively reviewed admissions of those patients in both areas during 1999. RESULTS: Admissions of HIV+ patients to IDW and PU generate 2.3% and 53.4% of hospital and PU stays, respectively. Both populations were equivalent in terms of mean age, CD4 count, viral load, prophylaxis for opportunistic infections, average stay, and death during stay. Male sex (91% vs. 74%), previous or current intravenous drug use (88% vs. 77%), and hepatitis C virus (HCV) seropositivity (97% vs. 82.6%) were more frequent in the PU than in the IDW. Multivariate analysis identified three factors as being independently related to admission from prison: longer time of known HIV infection (average 3.3 years; 95% CI 1.9-4.6), no previous antiretroviral treatment (odds ratio [OR] 2.95; 95% CI 1.46-6.0), and admission due to tuberculosis (OR 2.5; 95% CI 1.03-6.0). CONCLUSION: HIV infection is still a serious medical problem in CF. Although imprisonment can provide access to health programs, HIV-infected prison patients suffer more frequently from tuberculosis and take less antiretroviral treatment.