Limited cross-border infections in patients newly diagnosed with HIV in Europe

Matti Ristola ja Jussi Sutinen kuuluvat työryhmään SPREAD ProgrammePeer reviewe

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece

The current study investigated the impact of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection on the rate of change of antiretroviral drugs after the initiation of highly active antiretroviral treatment (HAART). The data on 1425 HIV-positive patients with recorded serology for hepatitis B surface antigen (HBsAg) were retrospectively analysed. The estimated rate of treatment change was slightly higher in the HBsAg-positive group (0.57 per year) compared with the HBsAg-negative group (0.50 per year). Although this difference was insignificant in multivariable modelling, the confidence intervals of the estimates barely included unity. Antiretroviral drug family, calendar period, prior exposure to antiretrovirals and the diagnosis of acquired immunodeficiency syndrome were independently associated with the number of drug alterations. A slight impact of co-infection on the frequency of treatment change after the beginning of HAART cannot be excluded. However, the paucity of studies on this issue necessitates the conduct of further research

Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: A cohort study and meta-analysis

Background. The effect of hepatitis B virus (HBV) infection on the natural history of human immunodeficiency virus (HIV) disease remains uncertain. Therefore, a retrospective cohort study was conducted to examine the influence of HIV-HBV coinfection on AIDS development and overall mortality. Moreover, our results were added to those of previous studies in a literature-based meta-analysis. Methods. Serum samples obtained from HIV-seropositive patients from 1984 through 2003 were retrospectively tested for hepatitis B surface antigen. Multivariable analyses were performed using Poisson and logistic regression models. For meta-analytic purposes, eligible articles were identified and relevant data were abstracted. Pooled estimates of effect were calculated applying fixed and random effects models. Results. The prevalence of chronic HBV infection (documented hepatitis B surface antigen seropositivity for >6 months) among 1729 HIV-positive patients was ∼6%. The multivariable analyses in our primary study revealed no significant impact of concomitant HIV-HBV infection on progression to AIDS and all-cause mortality. However, a meta-analysis performed on data from 12,382 patients enrolled in 11 studies revealed a significant effect of HIV- HBV coinfection on overall mortality (pooled effect estimate, 1.36; 95% confidence interval, 1.12-1.64). The increased rate of death among coinfected individuals was observed in the meta-analyses of studies conducted both before (pooled effect estimate, 1.60; 95% confidence interval, 1.07-2.39) and after (pooled effect estimate, 1.28; 95% confidence interval, 1.03-1.60) commencement of highly active antiretroviral therapy. Conclusions. HIV-HBV coinfection seems to affect all-cause mortality, and strategies to reduce liver damage in patients coinfected with HIV and HBV are justified. © 2009 by the Infectious Diseases Society of America. All rights reserved

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece

The current study investigated the impact of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection on the rate of change of antiretroviral drugs after the initiation of highly active antiretroviral treatment (HAART). The data on 1425 HIV-positive patients with recorded serology for hepatitis B surface antigen (HBsAg) were retrospectively analysed. The estimated rate of treatment change was slightly higher in the HBsAg-positive group (0.57 per year) compared with the HBsAg-negative group (0.50 per year). Although this difference was insignificant in multivariable modelling, the confidence intervals of the estimates barely included unity. Antiretroviral drug family, calendar period, prior exposure to antiretrovirals and the diagnosis of acquired immunodeficiency syndrome were independently associated with the number of drug alterations. A slight impact of co-infection on the frequency of treatment change after the beginning of HAART cannot be excluded. However, the paucity of studies on this issue necessitates the conduct of further research. </jats:p

Prevalence of resistance-associated mutations in newly diagnosed HIV-1 patients in Greece

The prevalence of HIV-1 drug resistance mutations in native patients has been previously shown to differ greatly with the geographic origin. The purpose of this study was to prospectively estimate the prevalence of HIV-1 drug resistance in Greece by analyzing a representative sample of newly HIV-1 diagnosed patients, as part of the SPREAD collaborative study. Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 101 newly diagnosed HIV-1 patients, in Greece, during the period September 2002-August2003, representing one-third of the total newly diagnosed HIV-1 patients in the same time period. The prevalence of HIV-1 drug resistance was estimated according to the IAS-USA mutation table taking into account a] I mutations in RT and only major mutations in PR region. The overall prevalence of resistance was 9% [95% confidence interval (CI): 4.2-16.2%]. The prevalence of mutations associated with resistance to NRTIs was 5% (95% Cl: 1.6-11.2%), for NNRTIs was 4% (95% CI: 1. 1-9.8%), while no major resistance mutations were found in PR. No multi-class resistance was detected in the study population. The prevalence of resistant mutations in the recent seroconverters was 22%. For two individuals, there was clear evidence for transmitted resistance based on epidemiological information for a known source of HIV-I transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%. (c) 2005 Elsevier B.V. All rights reserved

Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences.Results: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability.Conclusions: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level. © 2012 Theys et al.; licensee BioMed Central Ltd

Limited cross-border infections in patients newly diagnosed with HIV in Europe

Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value &lt;0.0001), in men who have sex with men (P-value &lt;0.0001), and in recently infected patients (P-value =0.045).Conclusions: Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics. © 2013 Frentz et al.; licensee BioMed Central Ltd