ABSTRACT
BACKGROUND: Recent studies have shown a decrease in the incidence of herpes zoster (HZ) among human immunodeficiency virus (HIV)-infected patients since the combined antiretroviral therapy (cART) era, but more data are needed on a possible increase in the risk early after cART initiation. METHODS: We studied HZ incidence and risk factors among patients followed in the French Hospital Database on HIV (FHDH) between 1992 and 2011. Standardized incidence ratios (SIRs) were used for comparison with the general population between 2005 and 2008. The risk of HZ following cART initiation (0-5 and ≥6 months) was studied with Poisson regression models. RESULTS: A total of 7167 cases of incident HZ were diagnosed among 91 044 individuals (583 125 person-years [PY]). The incidence declined significantly, from 2955 per 100 000 PY in 1992-1996 to 628 per 100 000 PY in 2009-2011. This decline was mainly explained by cART (relative risk [RR], 0.60; 95% confidence interval {CI}, .57-.64). The risk of HZ was associated with low CD4 cell counts, high HIV RNA levels, low CD4/CD8 ratios, and prior AIDS. Compared to the general population, the risk of HZ was higher in HIV-infected patients (overall SIR, 2.7; 95% CI, 2.6-2.9), particularly those aged 15-44 years (SIR, 4-6). In ART-naive patients, a moderate increase in the HZ risk was observed during the first 6 months of cART, with a peak at 3 months (RR, 1.47; 95% CI, 1.26-1.73), a finding that disappeared after adjustment for the current CD4 cell count (RR, 1.03; 95% CI, .81-1.32). CONCLUSIONS: The risk of HZ has declined markedly among HIV-infected patients in the cART era, but remains 3 times higher than in the general population. The risk increases moderately during the first 6 months of cART.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active , HIV Infections/complications , HIV Infections/drug therapy , Herpes Zoster/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Risk Assessment , Young AdultABSTRACT
OBJECTIVE: A recent consensus defines "late presentation" (LP) during the course of HIV infection as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells per cubic millimeter. Here, using this new definition, we examined the frequency and predictors of LP and its impact on mortality. METHODS: In antiretroviral-naive patients enrolled in the French Hospital Database on HIV between 2003 and 2009, we studied risk factors for LP by multivariable logistic regression. The impact of LP on mortality was analyzed according to the level of immunodeficiency by using Cox multivariable models adjusted for potential confounders, with follow-up categorized into 0-6, 6-12, and 12-48 months. RESULTS: There were 11,038 (53.9%) late presenters among the 20,496 patients included in the study. Compared with patients presenting for care with CD4 ≥350 cells per cubic millimeter, patients presenting with AIDS had a very high risk of death with crude hazard ratio ranging from 48.3 during the first 6 months of follow-up to 4.8 during months 12-48; the corresponding values among AIDS-free patients with CD4 ≤200 cells per cubic millimeter were 8.1 and 2.3. Importantly, patients presenting with CD4 between 200 and 350 cells per cubic millimeter also had a significantly increased risk of death beyond 6 months of follow-up (hazard ratio: 3.0 and 1.8 for months 6-12 and 12-48, respectively). Results were similar after adjustment. CONCLUSIONS: LP with HIV infection is still very frequent in France and is associated with higher mortality, even among patients with only moderate immunodeficiency. Encouraging early testing and access to care is still urgently needed.
Subject(s)
HIV Infections/epidemiology , HIV Infections/mortality , Survival Rate , Adult , Age of Onset , CD4 Lymphocyte Count , Databases, Factual/statistics & numerical data , Female , France/epidemiology , HIV Infections/immunology , HIV Infections/virology , Hospitals , Humans , Male , Middle Aged , Prevalence , Proportional Hazards Models , Risk Factors , Young AdultSubject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , Pyrrolidinones/administration & dosage , Adult , Aged , CD4 Lymphocyte Count , Female , Genotype , HIV-1/isolation & purification , Humans , Male , Middle Aged , Raltegravir Potassium , Treatment Outcome , Viral LoadSubject(s)
Chronic Disease/nursing , Vulnerable Populations , Chronic Disease/prevention & control , Diabetes Mellitus/diagnosis , Diabetes Mellitus/nursing , France , HIV Infections/diagnosis , HIV Infections/nursing , Health Services Needs and Demand , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/nursing , Skin Diseases/diagnosis , Skin Diseases/nursing , Smoking/adverse effects , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/nursingABSTRACT
Although HIV-1 Vpr displays several functions in vitro, limited information exists concerning their relevance during infection. Here, we characterized Vpr variants isolated from a rapid and a long-term non-progressor (LTNP). Interestingly, vpr alleles isolated from longitudinal samples of the LTNP revealed a dominant sequence that subsequently led to diversity similar to that observed in the progressor patient. Most of primary Vpr proteins accumulated at the nuclear envelope and interacted with host-cell partners of Vpr. They displayed cytostatic and proapoptotic activities, although a LTNP allele, harboring the Q65R substitution, failed to bind the DCAF1 subunit of the Cul4a/DDB1 E3 ligase and was inactive. This Q65R substitution correlated with impairment of Vpr docking at the nuclear envelope, raising the possibility of a functional link between this property and the Vpr cytostatic activity. In contradiction with published results, the R77Q substitution, found in LTNP alleles, did not influence Vpr proapoptotic activity.
