Poor recognition of HIV-1 Nef protein by CD8 T cells from HIV-1-infected children: impact of age.

Recognition of various HIV proteins by CD8 T cells from HIV-infected children was determined by two functional assays. First, using an Elispot assay, we show that 80% of patients recognized Gag, 77% recognized Pol, 61% recognized Env, 44% recognized Nef and 29% recognized Vif. Frequencies of Gag-, Pol-, and Env-specific IFN-gamma producing CD8 T cells were higher than frequencies of Nef and Vif-specific CD8 T cells.

Characteristics of HIV-infected children recently diagnosed in Paris, France.

Pediatric HIV-1 infections are still being diagnosed in France, despite the efficacy of prophylactic treatment to prevent mother-to-child transmission. To describe the characteristics and mode of infection of these children, we retrospectively analysed data of 59 children diagnosed with the HIV-1 infection between January 2000 and June 2005 in a Parisian university hospital. Twenty of these children had been born in France, and none had received appropriate prophylaxis (insufficient, not taken or given too late).

CD4 percentages and total lymphocyte counts as early surrogate markers for pediatric HIV-1 infection in resource-limited settings.

The early diagnosis of pediatric HIV-1 infection is a critical issue in resource-limited settings to prioritize eligibility for antiretroviral therapy among HIV-1-infected children. A case-control study was performed within the ANRS 1201/1202 Ditrame Plus cohort (Abidjan, Côte d'Ivoire) to assess the usefulness of CD4+ T-cell percentage (CD4%) and total lymphocyte count (TLC) measured early in life in African children born to HIV-1-infected mothers. Using plasma HIV-1 RNA testing at 4 weeks of life as gold standard, CD4% and TLC were determined at month 3 and 6 in all 33 children HIV-1-infected in utero or intrapartum/early postpartum (cases) born to mothers receiving peripartum antiretroviral prophylaxis.

Description of an adenovirus A31 outbreak in a paediatric haematology unit.

Adenovirus infections result in significant morbidity and mortality in allogeneic haematopoietic stem cell transplanted (hSCT) children. Adenovirus from species C and B account for more than 90% of adenoviruses recovered after hSCT. However, infections due to adenovirus A31 have been increasingly reported in recent years.

Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy.

Background: Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients.

Methods: A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin.

HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time.

Objective: Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in circulating virions and intracellular HIV strains.

Patients And Methods: Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients.

CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients.

Background: Treatment initiation at the time of primary human immunodeficiency virus (HIV) type 1 (HIV-1) infection has become less frequent in recent years.

Methods: In the French prospective PRIMO Cohort, in which patients are enrolled at the time of primary HIV-1 infection, 30% of the 552 patients recruited during 1996-2004 did not start receiving antiretroviral treatment during the first 3 months after diagnosis. We analyzed the patients' clinical and immunological outcomes and examined potential predictors of disease progression.

Sustained control of viremia following therapeutic immunization in chronically HIV-1-infected individuals.

Objective: Viral rebounds inevitably follow interruption of antiretroviral treatment in HIV-1-infected individuals. The randomized ANRS 093 aimed at investigating whether a therapeutic immunization was effective in containing the long-term viral replication following discontinuation of antiretroviral drugs in patients.

Methods: Seventy HIV-1-infected patients effectively treated with antiretroviral drugs were randomized to continue treatment alone or in combination with four boosts of ALVAC 1433 and HIV-LIPO-6T vaccines followed by three cycles of subcutaneous interleukin-2.

Low risk of nevirapine resistance mutations in the prevention of mother-to-child transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan, Cote d'Ivoire.

The frequency of resistance mutations was estimated in the cohort of Agence Nationale de Recherches sur le SIDA Ditrame Plus, a study that evaluated the combination of short-course zidovudine (ZDV) plus lamivudine (3TC) and single-dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). The frequency with which resistance mutations were detected in mothers at week 4 postpartum was 1.14% (95% confidence interval [CI], 0.

Genotypic human immunodeficiency virus type 1 drug resistance in highly active antiretroviral therapy-treated children in Abidjan, Côte d'Ivoire.

Objective: To estimate the frequency of human immunodeficiency virus type 1 (HIV-1) displaying genotypic drug resistance in highly active antiretroviral therapy (HAART)-treated children in Abidjan.

Methods: Among the 269 HIV-1-infected children enrolled in the ANRS 1278 prospective observational cohort between October 2000 and September 2003, 115 [median age, 6.35 years (range, 1.

Quantitation of HIV-1 RNA in breast milk by real time PCR.

HIV-1 RNA in breast milk is a strong predictor of HIV-1 transmission through breastfeeding. In the present report, breast milk samples from HIV-1 uninfected donors were spiked with dilution of quantified culture supernatant from HIV-1(NDK) infected PBMC. Two RNA extraction techniques based on silica extraction, Nuclisens (BioMerieux) and Triazol (Qiagen), two techniques based on guanidine thiocynanate/chloroforme extraction, TRIzol (Life Technologie) and Amplicor HIV-1 Monitor (Roche Diagnostic Systems), and one technique based on electrostatic adsorption on iron oxide micro beads (Promega) were compared.

A virologic survey of patients admitted to a critical care unit for acute cardiorespiratory failure.

Objective: To document the prevalence of respiratory virus infections in patients with chronic cardiac or pulmonary disorders admitted to a critical care unit for acute cardiorespiratory failure.

Design, Setting, Patients: The study took place in a critical care unit during two consecutive winters. All patients admitted to the unit for acute respiratory or cardiac failure were enrolled.

Detailed analysis of the genetic evolution of influenza virus during the course of an epidemic.

The genetic variability of influenza virus is usually studied with sequences selected over numerous years and countries, and rarely within a single season. Here we examined the viral evolution and the correlation between genetic and clinical features during an epidemic. From a French prospective household-based study in 1999-2000, 99 infected patients were randomly selected.

Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial.

Background: Whether structured treatment interruptions (STIs) can induce anti-HIV immune response and control HIV replication following discontinuation of highly active antiretroviral therapy (HAART) in patients with primary HIV infection is controversial.

Methods: In this multicenter, prospective trial, patients with early symptomatic primary HIV infection were given HAART continuously for 34 weeks. Afterward, patients with plasma viral load (PVL) <50 copies/mL entered the STI phase, which consisted of 3 consecutive periods of 2, 4, and 8 weeks off HAART, each separated by 12 weeks on HAART.

The frequency of HIV-specific interferon- gamma -producing CD8 T cells is associated with both age and level of antigenic stimulation in HIV-1-infected children.

Ex vivo interferon (IFN)- gamma -producing CD8 T cells specific for human immunodeficiency virus (HIV) Env, Gag, and Pol antigens were measured in the peripheral blood of 55 children not receiving highly active antiretroviral therapy (HAART) and 70 children receiving HAART. In children not receiving HAART, the frequency of HIV-specific IFN- gamma -producing CD8 T cells was positively correlated with age and was not associated with plasma viral load or CD4 T cell levels. In children receiving HAART, the frequency of HIV-specific IFN- gamma -producing CD8 T cells was directly correlated with plasma viral load, and its association with age remained significant.

Hepatitis C virus in the semen of men coinfected with HIV-1: prevalence and origin.

Objective: To compare the prevalence of hepatitis C (HCV) RNA in semen from men infected with HCV and those coinfected with HIV-1/HCV and to study the origin of HCV shed in semen.

Design: Two prospective studies (HC EP09 and BINECO) included 120 HCV-positive men, 82 coinfected with HIV-1; all had positive HCV RNA detection in blood.

Methods: Paired blood and semen samples were collected for HCV RNA detection and quantification in seminal plasma and in blood serum; repeated semen samples were obtained for 45 men.

HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication.

We identified a total 15 patients who have maintained undetectable plasma HIV RNA loads without antiretroviral treatment for >10 years from cohorts of 1300 and 1551 patients infected with human immunodeficiency virus (HIV). These 15 patients, whom we have referred to as "HIV controllers," are characterized by a low HIV DNA load in peripheral blood mononuclear cells and by a strong HIV-specific immune response.

In HIV type 1-infected children cytotoxic T lymphocyte responses are associated with greater reduction of viremia under antiretroviral therapy.

The evolution of the HIV-specific CD8+ T cell response in patients receiving potent combination therapy has been well documented in adult patients. However, no study reported whether baseline HIV-specific CD8+ T cell response is linked to treatment outcome. The aims of this study were to investigate both the impact of baseline memory cytotoxic T lymphocytes (CTL) on treatment outcome and the effect of potent therapy on memory HIV-specific CTL in HIV-1-infected pediatric patients.

Causal pathways of the effects of age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on AIDS development.

Objective: To investigate the causal pathways by which age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles influence progression to AIDS.

Design: Analysis of follow-up data from 2 cohort studies among homosexual men (n=400), having >10 years of follow-up.

Methods: The effects of the 4 cofactors on the CD4 and HIV-1 RNA trajectories after seroconversion were modeled in a random-effects model.

Transfer and evaluation of an automated, low-cost real-time reverse transcription-PCR test for diagnosis and monitoring of human immunodeficiency virus type 1 infection in a West African resource-limited setting.

There is an urgent need for low-cost human immunodeficiency virus type 1 (HIV-1) viral load (VL) monitoring technologies in resource-limited settings. An automated TaqMan real-time reverse transcription-PCR (RT-PCR) assay was transferred to the laboratory of the Centre de Diagnostic et de Recherches sur le SIDA, Abidjan, Côte d'Ivoire, and assessed for HIV-1 RNA VL testing in 806 plasma samples collected within four ANRS research programs. The detection threshold and reproducibility of the assay were first determined.

Early levels of HIV-1 DNA in peripheral blood mononuclear cells are predictive of disease progression independently of HIV-1 RNA levels and CD4+ T cell counts.

Background: The objective of this work was to assess the role of human immunodeficiency virus (HIV) reservoirs in the risk of disease progression, by studying the relationship between HIV DNA level in peripheral blood mononuclear cells (PBMCs) and progression toward acquired immunodeficiency syndrome (AIDS).

Methods: HIV-1 DNA levels in PBMCs were determined by quantitative polymerase chain reaction for 383 patients enrolled in the SEROCO Cohort Study who had experienced seroconversion and had been followed up for >8 years. We compared the predictive values of HIV DNA level, HIV RNA level, and CD4+ cell count.

Combination of HIV-1-specific CD4 Th1 cell responses and IgG2 antibodies is the best predictor for persistence of long-term nonprogression.

Background: Strong T cell and antibody responses to human immunodeficiency virus (HIV), low virus production, and some genetic traits have been individually associated with nonprogression of HIV infection, but the best correlate with protection against disease progression remains unknown.

Methods: We prospectively followed 66 untreated long-term nonprogressors and analyzed relationships between HIV-1-specific CD4 T helper (Th) 1 and CD8 T cell responses and HIV-1-specific antibodies, HIV-1 RNA and proviral DNA loads, host genes, and CD4 Th1 cell counts at entry into the study and 4 years later.

Results: HIV-1 p24-specific CD4 Th1 cell proliferation, interferon (IFN)- gamma production, and IFN- gamma -producing cell frequencies at entry significantly and negatively correlated with HIV-1 RNA and proviral DNA loads and were independent of CD4 Th1 cell counts and host genes.

A vaccinia-based elispot assay for detection of CD8+ T cells from HIV-1 infected children.

HIV-specific CD8+ T lymphocytes participate in the control of viral replication in infected patients. These responses are of low intensity in young infants and are decreased by antiretroviral therapy. In the present study, we report on a recombinant Vaccinia virus (rVV)-based Elispot assay for the detection of HIV-specific CD8+ T cells immediately after isolation of peripheral blood mononuclear cells (PBMC).

Undetectable viremia without antiretroviral therapy in patients with HIV seroconversion: an uncommon phenomenon?

Background: The objective of this study was to identify the frequency and characteristics of patients with human immunodeficiency virus (HIV) infection who had spontaneously achieved viremia below the detection limit of either 400 or 500 copies/mL (depending on the test used) and to describe the duration of undetectable viremia without antiretroviral therapy (ART).

Methods: In the French Agence Nationale de Recherches sur le SIDA SEROCO cohort, 426 patients with HIV seroconversion (i.e.