A critique of the use of DNA synthesis as a measure of the effect of mitogens on lymphocytes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44188/1/10540_2005_Article_BF01116174.pd

Clinical Progression Rates by CD4 Cell Category Before and After the Initiation of Combination Antiretroviral Therapy (cART)

OBJECTIVE: Rates of AIDS defining event (ADE), serious ADE and death by CD4 and HIV RNA categories before and after combination antiretroviral therapy (cART) initiation are lacking for high CD4 counts. METHODS: Event rates were estimated within CD4 cell strata using a Poisson regression model adjusting for sex, exposure category, age, and current HIV RNA (<4, 4-4.99, > or =5 log copies/ml), and including an interaction term between the CD4 cell count and cART indicator. RESULTS: 7317 and 6376 persons contributed to "naïve " and "cART " groups respectively, of whom 3911 contributed to both. At the same CD4 level, the risk of ADE was nearly 2 fold higher during naive follow-up compared to cART for CD4 <500 cells/mm(3). However, after adjustment for current HIV RNA, the risk of ADE became similar for both groups except for CD4 count <200 cells/mm(3) when it is 35% (6-72%) higher for naives. The same results were observed for the risk of serious ADE. There was no evidence of a difference in risk of death between naive and cART follow-up at specific CD4 categories even after adjustment for HIV RNA. CONCLUSION: Within CD4 cell strata above 200 cells/mm(3), the risk of ADE before ART initiation is higher than it is following cART initiation

An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration.

BACKGROUND: Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. METHODS: We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve). RESULTS: Most definitions classify ∼ 1% as ECs with median HIV-RNA 43-903 copies/ml and median CD4>500 cells/mm(3). Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥ 92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements 90% of measurements <400 copies/ml over ≥ 10 years be used to define this phenotype

HIV Testing and Diagnosis Rates in Kiev, Ukraine: April 2013-March 2014

Data from Ukraine on risk factors for HIV acquisition are limited. We describe the characteristics of individuals testing for HIV in the main testing centres of the Ukrainian capital Kiev, including HIV risk factors, testing rates, and positivity rates. As part of a larger study to estimate HIV incidence within Kiev City, we included questions on possible risk factors for HIV acquisition and testing history to existing systems in 4 infectious disease clinics. Data were provided by the person requesting an HIV test using a handheld electronic tablet. All persons (≥16 yrs) presenting for an HIV test April 2013-March 2014 were included. Rates per 100,000 were calculated using region-specific denominators for Kiev. During the study period 6370 individuals tested for HIV, equivalent to a testing rate of 293.2 per 100,000. Of these, 467 (7.8%) were HIV-positive, with the highest proportion positive among 31-35 year olds (11.2%), males (9.4%), people who inject drugs (PWID) (17.9%) and men who have sex with men (MSM) (24.1%). Using published population size estimates of MSM, diagnosis rates for MSM ranged from 490.6 to 1548.3/100,000. A higher proportion of heterosexual women compared to heterosexual men reported contact with PWID, (16% vs. 4.7%) suggesting a bridging in risk between PWID and their sexual partners. Collection of HIV risk factor information in Kiev, essential for the purposes of developing effective HIV prevention and response tools, is feasible. The high percentage of MSM among those testing positive for HIV, may indicate a significant level of undisclosed sex between men in national figures

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Objective: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. Methods: HICs were identified in COHERE on the basis of \ue2\u89\ua55 consecutive viral loads (VL) \ue2\u89\ua4500 copies/mL over \ue2\u89\ua51 year whilst ART-naive, with the last VL \ue2\u89\ua4500 copies/mL measured \ue2\u89\ua55 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL &gt;2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. Results: We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. Discussion: Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs

A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations

Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013–March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56–7.50]); risk group (OR, 5.65 [95% CI, 3.27–9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64–4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07–3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10–3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31–.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions Our findings suggest high levels of transmission and bridging between risk groups

[Cancer and HIV infection.]

International audienceAvec l'arrivée des nouvelles combinaisons antirétrovirales, l'incidence des cancers classant SIDA a fortement diminué et l'incidence des cancers ne définissant pas le SIDA est désormais plus élevée. les cancers dont le risque est augmenté avec l'immunodépression sont le plus souvent associés à une infection virale. Dans le contexte de l'infection à VIH, certains virus pourraient avoir un effet oncogène directement ou via un processus de facilitation, l'immunodépression limitant la capacité de l'hôte de contrôler précocement l'expansion tumorale ou la réplication virale. Les taux de survie après un diagnostic de cancer sont significativement plus faibles chez les personnes vivant avec le VIH que dans la population générale posant la question de la sévérité de leur présentation, et aussi celle de leur prise en charge

[Cancer and HIV infection.]

International audienceAvec l'arrivée des nouvelles combinaisons antirétrovirales, l'incidence des cancers classant SIDA a fortement diminué et l'incidence des cancers ne définissant pas le SIDA est désormais plus élevée. les cancers dont le risque est augmenté avec l'immunodépression sont le plus souvent associés à une infection virale. Dans le contexte de l'infection à VIH, certains virus pourraient avoir un effet oncogène directement ou via un processus de facilitation, l'immunodépression limitant la capacité de l'hôte de contrôler précocement l'expansion tumorale ou la réplication virale. Les taux de survie après un diagnostic de cancer sont significativement plus faibles chez les personnes vivant avec le VIH que dans la population générale posant la question de la sévérité de leur présentation, et aussi celle de leur prise en charge

Robustness of case-control studies of genetic factors to population stratification : magnitude of bias and type I error

Case-control studies of genetic factors are prone to a special form of confounding called population stratification, whenever the existence of one or more subpopulations may lead to a false association, be it positive or negative. We quantify both the bias (in terms of confounding risk ratio) and the probability of false association (type I error) in the most unfavorable situation in which only one high-risk subpopulation is hidden within the studied population, considering different scenarios of population structuring and varying sample sizes. In accord with previous work, we find that the bias is likely to be small in most cases. In addition, we show that the same applies to the associated type I error whenever the subpopulation is small in proportion. For instance, when the hidden subpopulation makes up 5% of the entire population, with an allelic frequency of 0.25 (versus 0.10) and a disease rate that is double, then the estimated bias is 1.07 and the type I error associated with a sample of 500 cases and 500 controls is 8% (instead of 5%). We also show that the type I error is substantially greater for a rare allele (frequency of 0.1) than for a common allele (frequency of 0.5) and analyze the pattern of increase of vulnerability to stratification bias with sample size. Based on our findings, we may therefore conclude that with moderate sample sizes the type I error associated with population stratification remains very limited in most realistic scenarios