Anna Esteve

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

BACKGROUND Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. METHODS The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, and stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude mortality rates were also calculated. FINDINGS 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996-99, 2000-02, and 2003-05, respectively. 2056 (4.7%) deaths were observed during the study period, with crude mortality rates decreasing from 16.3 deaths per 1000 person-years in 1996-99 to 10.0 deaths per 1000 person-years in 2003-05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36.1 (SE 0.6) years to 49.4 (0.5) years. Women had higher life expectancies than did men. Patients with presumed transmission via injecting drug use had lower life expectancies than did those from other transmission groups (32.6 [1.1] years vs 44.7 [0.3] years in 2003-05). Life expectancy was lower in patients with lower baseline CD4 cell counts than in those with higher baseline counts (32.4 [1.1] years for CD4 cell counts below 100 cells per muL vs 50.4 [0.4] years for counts of 200 cells per muL or more). INTERPRETATION Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients. The average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries.

HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects

Highly active antiretroviral therapy (HAART) results in potent and durable suppression of HIV-1 viremia. However, HIV-1 replication resumes if therapy is interrupted. Although it is generally believed that active replication has been halted in individuals on HAART, immune activation and inflammation continue at abnormal levels, suggesting continued, low-level viral replication. To assess whether active replication might be driving immune activation in HAART, we examined the impact of treatment intensification with the integrase inhibitor raltegravir on viral complementary DNA and immune activation parameters. In the presence of raltegravir, linear HIV-1 cDNA is prevented from integrating into chromatin and is subsequently converted to episomal cDNAs. Raltegravir intensification of a three-drug suppressive HAART regimen resulted in a specific and transient increase in episomal DNAs in a large percentage of HAART-suppressed subjects. Furthermore, in subjects with these episomal DNAs, immune activation was higher at baseline and was subsequently normalized after raltegravir intensification. These results suggest that, despite suppressive HAART, active replication persists in some infected individuals and drives immune activation. The ability of raltegravir intensification to perturb the reservoir that supports active replication has implications for therapeutic strategies aimed at achieving viral eradication.

When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study.

BACKGROUND Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. OBJECTIVE To identify the optimal CD4 cell count at which cART should be initiated. DESIGN Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. SETTING HIV clinics in Europe and the Veterans Health Administration system in the United States. PATIENTS 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. MEASUREMENTS Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. RESULTS Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. LIMITATIONS CD4 cell count at cART initiation was not randomized. Residual confounding may exist. CONCLUSION Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

Usefulness of Urinary Antigen Detection by an Immunochromatographic Test for Diagnosis of Pneumococcal Pneumonia in Children

ABSTRACT We evaluated an immunochromatographic assay detecting pneumococcal antigen in urine samples from children diagnosed with pneumococcal pneumonia. The sensitivity and specificity of the immunochromatographic test with nonconcentrated urine (NCU) were 86.7 and 62.9%, respectively; with concentrated urine (CU), they were 100 and 11.7%, respectively. Pneumococcal antigen was also detected in 42.5% of NCU and 87.1% of CU samples from nasopharyngeal carriers. This is a nonspecific test for the diagnosis of pneumococcal pneumonia in children, particularly the very young.

Risk factors for human Herpesvirus 8 infection and AIDS-associated Kaposi's sarcoma among men who have sex with men in a European multicentre study

We aimed to identify risk factors for Kaposis sarcoma (KS) among HIV‐positive patients and behaviors associated with human Herpesvirus 8 (HHV‐8) infection, as well as to assess KS incidence and mortality rates longitudinally. To fulfill the first objective, a European case‐control study was designed in the early 1990s (each KS case was matched to 2 controls with another AIDS indicative disease). After the discovery of HHV‐8, serology testing enabled us to assess risk factors for KS development among HHV‐8 and HIV‐1 coinfected men who have sex with men (MSM), as well as risk factors for HHV‐8 infection. HHV‐8 seroprevalence was determined using a latent immunofluorescence assay. Relevant information was obtained by means of a questionnaire and medical charts review. Assessment of risk factors for KS development and HHV‐8 infection was performed using conditional and unconditional logistic regression models, respectively. A low CD4 count was the only significant risk factor for KS. HHV‐8 infection was most strongly linked to the number of life‐time sex partners, and multiple body fluids such as saliva and semen are quite likely involved in sexual transmission. Longitudinal follow up showed a significant protective role for highly‐active antiretroviral therapy (HAART) both on KS development and mortality of KS patients. Although more conclusive data from cohort studies are needed to better define specific transmission mechanisms for HHV‐8, our results contribute to explain why KS incidence is higher among MSM, and the decreasing KS incidence trend observed in countries with universal access to HAART.

Prevalence of human immunodeficiency virus, Chlamydia trachomatis, and Neisseria gonorrhoeae and risk factors for sexually transmitted infections among immigrant female sex workers in Catalonia, Spain.

Objectives: To determine the prevalence of human immunodeficiency virus (HIV), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) among immigrant female sex workers (FSW) according to their geographic area of origin and identify possible risk factors independently associated with current infection with CT and/or NG. Study Design: Cross-sectional study of 357 FSW in Catalonia in 2005. Information on sociodemographic and sex work characteristics, use of alcohol and drugs, sexual practices, and the use of social and health care services was collected. Oral fluid and urine samples were collected to determine the prevalence of HIV and CT/NG, respectively. Factors independently associated with CT/NG were assessed using multivariate logistic regression models. Results: A total of 36.4% of women were from Eastern Europe, 34.5% from Latin America, and 29.1% from Africa. Overall CT and NG prevalence were 5.9% [95% confidence interval (CI): 3.7–8.9] and 0.6% (95% CI: 0.1–2.0), respectively. No differences were observed by geographic origin. Three African women were HIV positive (overall HIV prevalence was 0.8%, 95% CI: 0.2–2.4). In multivariate analysis, younger age and unprotected sex with clients were associated with the presence of CT/NG. Conclusions: The prevalence of sexually transmitted infections among FSW in Catalonia was lower than in other European countries. Even though the prevalence of HIV was only 0.8%, it could increase in the future given the high vulnerability of these women and their wide geographic mobility. It is necessary to continue with the work carried out by nongovernmental organizations (harm reduction programs, outreach programs, and safe sex workshops) as well as to facilitate the access to health centers, especially for the youngest women.

Características clinicoepidemiológicas y tendencias en el tratamiento antirretroviral de una cohorte de pacientes con infección por el virus de la inmunodeficiencia humana. Cohorte PISCIS

Fundamento y objetivo: Los objetivos de este estudio fueron describir el proceso de implementacion de la cohorte PISCIS y las caracteristicas clinicoepidemiologicas y las tendencias en el tratamiento antirretroviral (TARV) de los pacientes con infeccion por el virus de la inmunodeficiencia humana (VIH) incluidos desde 1998 hasta 2003. Pacientes y metodo: Estudio de cohorte prospectivo de pacientes con infeccion por el VIH de 16 anos de edad o mayores atendidos en primera visita en 10 hospitales de Cataluna y uno de las Baleares. El analisis estadistico de las tendencias se realizo mediante el test de la *2 de Mantel. Resultados: Se incluyo a un total de 5.968 pacientes (edad media: 39,5 anos; 75% varones) con un tiempo medio de seguimiento de 26,4 meses (13.130 personas-ano). Del total, 2.763 fueron nuevos diagnosticos, en los que la via de transmision mas frecuente fue la heterosexual (43%), seguida de la homosexual (31%). Se observo una tendencia significativamente creciente en la proporcion de sujetos de edad inferior a 35 anos e inmigrantes. Un 43% tenian una cifra de linfocitos CD4 inferior a 200 celulas/µl en la determinacion mas cercana al diagnostico de la infeccion por el VIH. Del total, un 87% estaban en TARV en el ano 2003. Entre los pacientes no tratados previamente que iniciaron pautas de TARV con 3 o mas farmacos, se observo una disminucion de las pautas que incluian inhibidores de la proteasa (del 85% en 1998 al 25% en 2003; p < 0,001), mientras que aumentaron otras que contenian inhibidores de la transcriptasa inversa no analogos y analogos de los nucleosidos. Conclusiones: Las cohortes de pacientes con infeccion por el VIH son viables en nuestro medio y tienen gran utilidad clinica y en salud publica. La via de transmision mas frecuente entre los nuevos diagnosticos es la heterosexual, el retraso en el diagnostico es elevado y las pautas de TARV han ido cambiando para adaptarse a las recomendadas por las guias.

Intensification of a raltegravir-based regimen with maraviroc in early HIV-1 infection.

Background:Latent HIV-1-infected cells generated early in the infection are responsible for viral persistence, and we hypothesized that addition of maraviroc to triple therapy in patients recently infected with HIV-1 could accelerate decay of the viral reservoir. Methods:Patients recently infected (<24 weeks) by chemokine receptor 5 (CCR5)-using HIV-1 were randomized to a raltegravir + tenofovir/emtricitabine regimen (control arm, n = 15) or the same regimen intensified with maraviroc (+MVC arm, n = 15). Plasma viral load, cell-associated HIV-1 DNA (total, integrated, and episomal), and activation/inflammation markers were measured longitudinally. Results:Plasma viral load decayed in both groups, reaching similar residual levels at week 48. Total cell-associated HIV-1 DNA also decreased in both groups during the first month, although subsequently at a slightly faster rate in the +MVC arm. The transient increase in two long terminal repeat (2-LTR) circles observed in both groups early after initiation of treatment decreased earlier in MVC-treated individuals. Early (week 12) increase of CD4+ T-cell counts was higher in the +MVC arm. Conversely, CD8+ T-cell counts and CD4+ T-cell activation decreased slower in the +MVC arm. Absolute CD4+ T-cell and CD8+ T-cell counts, immune activation, CD4+/CD8+ T-cell ratio, and soluble inflammation markers were similar in both arms at the end of the study. Conclusion:Addition of maraviroc in early integrase inhibitor-based treatment of HIV-1 infection results in faster reduction of 2-LTR+ newly infected cells and recovery of CD4+ T-cell counts, and a modest reduction in total reservoir size after 48 weeks of treatment. Paradoxically, CCR5 blockade also induced a slower decrease in plasma viremia and immune activation.

Comparison of the Avidity Index Method and the Serologic Testing Algorithm for Recent Human Immunodeficiency Virus (HIV) Seroconversion, Two Methods Using a Single Serum Sample for Identification of Recent HIV Infections

ABSTRACT A study was designed to compare an avidity index method to the serologic testing algorithm for recent human immunodeficiency virus (HIV) seroconversion (STARHS) for the detection of recent HIV infection. One hundred sixty HIV-positive sera were tested. Both techniques performed similarly in identifying recent infections, although STARHS tended to misclassify more individuals that had long-standing infection as being recently infected.

Correlates of intensive alcohol and drug use in men who have sex with men in Catalonia, Spain

BACKGROUND The objectives of the study were to determine the prevalence of alcohol and drug use before or during sex among men who have sex with men (MSM) in Catalonia during 2006, and to identify factors associated with variables of intensive alcohol and drug use. METHODS Cross-sectional study using self-administered questionnaires. Men were recruited in saunas, sex shops, bars and a public park and by mail to all the members of the Catalonia Gay Federation. RESULTS 19.6% of men said they were frequent users of alcohol, some type of drug (21.7%), or that they were multidrug users (18%) in the last 12 months. The multivariate analysis showed an association between having suffered discrimination and frequent alcohol and multidrug use. Being human immunodeficiency virus (HIV)-positive was associated with frequent use of drugs and multidrug use. Associations between substance use and sexual risk behaviour also emerged. CONCLUSION The high percentage of MSM who use alcohol and drugs before and during sex and association between these substances and sexual risk behaviours reveals the need to intensify interventions to reduce their levels of use and/or to reduce the associated damage and risks. These programs must try to cover MSM-specific psychosocial aspects and include prevention for HIV-positive men.