Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study

BACKGROUND Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina. METHODS 13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death. FINDINGS During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis. INTERPRETATIONS There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region

Five-year trends in epidemiology and prevention of mother-to-child HIV transmission, St. Petersburg, Russia: results from perinatal HIV surveillance

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic in Russia has increasingly involved reproductive-aged women, which may increase perinatal HIV transmission.</p> <p>Methods</p> <p>Standard HIV case-reporting and enhanced perinatal HIV surveillance systems were used for prospective assessment of HIV-infected women giving birth in St. Petersburg, Russia, during 2004-2008. Trends in social, perinatal, and clinical factors influencing mother-to-child HIV transmission stratified by history of injection drug use, and rates of perinatal HIV transmission were assessed using two-sided χ²or Cochran-Armitage tests.</p> <p>Results</p> <p>Among HIV-infected women who gave birth, the proportion of women who self-reported ever using injection drugs (IDUs) decreased from 62% in 2004 to 41% in 2008 (<it>P </it>< 0.0001). Programmatic improvements led to increased uptake of the following clinical services from 2004 to 2008 (all <it>P </it>< 0.01): initiation of antiretroviral prophylaxis at ≤28 weeks gestation (IDUs 44%-54%, non-IDUs 45%-72%), monitoring of immunologic (IDUs 48%-64%, non-IDUs 58%-80%) and virologic status (IDUs 8%-58%, non-IDUs 10%-75%), dual/triple antiretroviral prophylaxis (IDUs 9%-44%, non-IDUs 14%-59%). After initial increase from 5.3% (95% confidence interval [CI] 3.5%-7.8%) in 2004 to 8.5% (CI 6.1%-11.7%) in 2005 (<it>P </it>< 0.05), perinatal HIV transmission decreased to 5.3% (CI 3.4%-8.3%) in 2006, and 3.2% (CI 1.7%-5.8%) in 2007 (<it>P </it>for trend <0.05). However, the proportion of women without prenatal care and without HIV testing before labor and delivery remained unchanged.</p> <p>Conclusions</p> <p>Reduced proportion of IDUs and improved clinical services among HIV-infected women giving birth were accompanied by decreased perinatal HIV transmission, which can be further reduced by increasing outreach and HIV testing of women before and during pregnancy.</p

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

VS411 reduced immune activation and HIV-1 RNA levels in 28 days: randomized proof-of-concept study for antiviral-hyperactivation limiting therapeutics.

A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4(+) T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects.Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests.VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4(+) T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: -1.47 log(10) copies/mL; CD4(+) T cell count: +135 cells/mm(3)) and fewest adverse events.VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system activation associated with HIV-1 disease. Rapid reductions in markers of immune system hyperactivation and cellular proliferation were obtained despite the fact that VS411 did not attain maximal suppression of HIV RNA, suggesting this effect was due to the HALT component.ITEudraCT 2007-002460-98

A Survery of ATRIPLA Use in Clinical Practise among Treatment-naïve HIV-positive Patients in Europe

EuroSIDA in EuroCoordinfo:eu-repo/semantics/nonPublishe

TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen

Objective: TMC125, a next generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA achieved by TMC125 monotherapy with that of a triple class, five-drug regimen, containing drugs from all three currently licensed classes (zidovudine, lamivudine, abacavir, indinavir and nevirapine). Methods: The decline in plasma HIV-1 RNA of 12 HIV-1 infected, antiretroviral (ART) naive patients treated for 1 week with TMC125 monotherapy was compared with that observed in the ERA study (n = 11). The plasma HIV-1 RNA elimination rate constant was calculated based on at least four plasma HIV-1 RNA measurements during the first week of treatment (first-order elimination) and compared using the Student's t test. Results: Median ages were 23 and 38 years for TMC125 and ERA patients, respectively (P = 0.001), median baseline plasma HIV-1 RNA levels were 4.2 and 4.8 log10 copies/ml (P = 0.001) and median baseline CD4 T-cell counts were 458 × 106 and 360 × 106 cells/l (P = 0.08). The median plasma HIV-1 RNA elimination rate constant was 0.68/day in TMC125 treated patients, and 0.56/day in ERA participants (P = 0.24). The median decline in plasma HIV-1 RNA after 7 days was 1.92 and 1.76 log 10 copies (P = 0.77) and the median increase of CD4 T cells was 119 × 106 and 60 × 106 cells/l, respectively (P = 0.29). Conclusion: Monotherapy with TMC125 in ART-naive, HIV-1-infected individuals resulted in a similar rate of decline of plasma HIV-1 RNA during 1 week of therapy as therapy with a five-drug regimen

TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen

Objective: TMC125, a next generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA achieved by TMC125 monotherapy with that of a triple class, five-drug regimen, containing drugs from all three currently licensed classes (zidovudine, lamivudine, abacavir, indinavir and nevirapine). Methods: The decline in plasma HIV-1 RNA of 12 HIV-1 infected, antiretroviral (ART) naive patients treated for 1 week with TMC125 monotherapy was compared with that observed in the ERA study (n = 11). The plasma HIV-1 RNA elimination rate constant was calculated based on at least four plasma HIV-1 RNA measurements during the first week of treatment (first-order elimination) and compared using the Student's t test. Results: Median ages were 23 and 38 years for TMC125 and ERA patients, respectively (P = 0.001), median baseline plasma HIV-1 RNA levels were 4.2 and 4.8 log(10) copies/ml (P = 0.001) and median baseline CD4 T-cell counts were 458 X 10(6) and 360 X 10(6) cells/l (P = 0.08). The median plasma HIV-1 RNA elimination rate constant was 0.68/day in TMC125 treated patients, and 0.56/day in ERA participants (P = 0.24). The median decline in plasma HIV-1 RNA after 7 days was 1.92 and 1.76 log(10) copies (P = 0.77) and the median increase of CD4 T cells was 119 X 10(6) and 60 X 106 cells/l, respectively (P = 0.29). Conclusion: Monotherapy with TMC125 in ART-naive, HIV-1-infected individuals resulted in a similar rate of decline of plasma HIV-1 RNA during 1 week of therapy as therapy with a five-drug regimen. (C) 2003 Lippincott Williams Wilkin