Bartosz Szetela

Transmitted HIV drug resistance in antiretroviral-treatment-naive patients from Poland differs by transmission category and subtype

OBJECTIVES The surveillance of HIV-transmitted drug resistance mutations (t-DRMs), including temporal trends across subtypes and exposure groups, remains a priority in the current management of the epidemic worldwide. METHODS A cross-sectional analysis of 833 treatment-naive patients from 9 of 17 Polish HIV treatment centres. Partial pol sequences were used to analyse drug resistance with a general time reversible (GTR)-based maximum likelihood algorithm used for cluster/pair identification. Mutation frequencies and temporal trends were investigated. RESULTS t-DRMs were observed in 9% of cases (5.8% for NRTI, 1.2% NNRTI and 2.0% PI mutations) and were more common among heterosexually infected (HET) individuals (13.4%) compared with MSM (8.3%, P = 0.03) or injection drug users (IDUs; 2.9%, P = 0.001) and in MSM compared with IDUs (P = 0.046). t-DRMs were more frequent in cases infected with the non-B variant (21.6%) compared with subtype B (6.6%, P < 0.001). With subtype B a higher mutation frequency was found in MSM compared with non-MSM cases (8.3% versus 1.8% for IDU + HET, P = 0.038), while non-B variants were associated with heterosexual exposure (30.4% for HET versus 4.8% for MSM, P = 0.019; versus 0 for IDU, P = 0.016). Trends in t-DRM frequencies were stable over time except for a decrease in NNRTI t-DRMs among MSM (P = 0.0662) and an NRTI t-DRM decrease in HET individuals (P = 0.077). With subtype B a higher frequency of sequence pairs/clusters in MSM (50.4%) was found compared with HET (P < 0.001) and IDUs (P = 0.015). CONCLUSIONS Despite stable trends over time, patterns of t-DRMs differed notably between transmission categories and subtypes: subtype B was associated with MSM transmission and clustering while in non-B clades t-DRMs were more common and were associated with heterosexual infections.

Molecular epidemiology of recent HIV‐1 infections in southern Poland

The genetic diversity of human immunodeficiency virus type 1 (HIV‐1) offers an opportunity to track the development of the epidemic across different populations. Viral pol gene fragments from 55 individuals of Polish origin with recent HIV‐1 infection identified in 2008–2010 in four Polish cities were analyzed. Viral sequences were compared with sequences from 100 individuals (reference group) infected before 2004. Viral spread among groups with different HIV transmission categories was compared using a phylogenetic approach. The majority of sequences from individuals with recent infection were subtype B (93%) within which four transmission clusters (18% of samples) were detected. Samples from men infected through sex between men and from persons infected through injecting drugs were broadly separated (P < 0.0001), while samples from individuals infected by heterosexual contacts were dispersed uniformly within phylogenetic tree (P = 0.244) inferred from viral sequences derived from individuals infected recently and the reference group. The percentage of samples from persons infected by heterosexual contacts which clustered with samples from men infected through sex between men was not significantly higher for those with recent infection (47%), compared to the reference group (36%). In conclusion, men infected by sex between men and individuals infected through injecting drugs appear to form separate HIV transmission networks in Poland. The recent spread of HIV‐1 among persons infected with subtype B by heterosexual contacts appears to be linked to both these groups. J. Med. Virol. 84:1857–1868, 2012.

Time trends in HIV-1 transmitted drug resistance mutation frequency in Poland.

In Poland, the HIV epidemic has shifted recently from being predominantly related to injection drug use (IDU) to being driven by transmissions among men‐who‐have‐sex‐with‐men (MSM). The number of new HIV cases has increased in the recent years, while no current data on the transmitted drug resistance associated mutations (tDRM) frequency trend over time are available from 2010. In this study, we analyze the temporal trends in the spread of tDRM from 2008 to 2013.

Expanding HIV-1 subtype B transmission networks among men who have sex with men in Poland

Introduction Reconstruction of HIV transmission links allows to trace the spread and dynamics of infection and guide epidemiological interventions. The aim of this study was to characterize transmission networks among subtype B infected patients from Poland. Material and methods Maximum likelihood phylogenenetic trees were inferred from 966 HIV-1 subtype B protease/reverse transcriptase sequences from patients followed up in nine Polish HIV centers. Monophyletic clusters were identified using 3% within-cluster distance and 0.9 bootstrap values. Interregional links for the clusters were investigated and time from infection to onward transmission estimated using Bayesian dated MCMC phylogeny. Results Three hundred twenty one (33.2%) sequences formed 109 clusters, including ten clusters of ≥5 sequences (n = 81, 8.4%). Transmission networks were more common among MSM (234 sequences, 68.6%) compared to other infection routes (injection drug use: 28 (8.2%) and heterosexual transmissions: 59 (17.3%) cases, respectively [OR:3.5 (95%CI:2.6–4.6),p<0.001]. Frequency of clustering increased from 26.92% in 2009 to 50.6% in 2014 [OR:1.18 (95%CI:1.06–1.31),p = 0.0026; slope +2.8%/year] with median time to onward transmission within clusters of 1.38 (IQR:0.59–2.52) years. In multivariate models clustering was associated with both MSM transmission route [OR:2.24 (95%CI:1.38–3.65),p<0.001] and asymptomatic stage of HIV infection [OR:1.93 (95%CI:1.4–2.64),p<0.0001]. Additionally, interregional networks were linked to MSM transmissions [OR:4.7 (95%CI:2.55–8.96),p<0.001]. Conclusions Reconstruction of the HIV-1 subtype B transmission patterns reveals increasing degree of clustering and existence of interregional networks among Polish MSM. Dated phylogeny confirms the association between onward transmission and recent infections. High transmission dynamics among Polish MSM emphasizes the necessity for active testing and early treatment in this group.

Pathogenesis of HIV-1 infection – chosen aspects

Summary Immunopathogenesis of HIV-1 infection is very complex but its understanding is vital for creating new and effective antiretroviral treatments and specific prophylaxis. The authors wanted to give the latest insight into the pathogenesis of HIV infection.

Nutritional support for patients living with HIV or AIDS

Summary Nutritional support for chronically ill patients is still perceived by medical professionals as a specialist field of expertise even though adequate supplementation of micro- and macroelements has been widely accepted as one of key factors in successful treatment of chronic conditions like diabetes, renal, hepatic and intestinal disease as well as HIV/AIDS. In all these cases prophylaxis of malnutrition and wasting has been proven to be cost-effective and in the case of HIV it has added value to cART alone in improving survival and quality of life.

Prevalence of Transmitted Drug-Resistance Mutations and Polymorphisms in HIV-1 Reverse Transcriptase, Protease, and gp41 Sequences Among Recent Seroconverters in Southern Poland

Background Monitoring of drug resistance-related mutations among patients with recent HIV-1 infection offers an opportunity to describe current patterns of transmitted drug resistance (TDR) mutations. Material/Methods Of 298 individuals newly diagnosed from March 2008 to February 2014 in southern Poland, 47 were deemed to have recent HIV-1 infection by the limiting antigen avidity immunoassay. Proviral DNA was amplified and sequenced in the reverse transcriptase, protease, and gp41 coding regions. Mutations were interpreted according to the Stanford Database algorithm and/or the International Antiviral Society USA guidelines. TDR mutations were defined according to the WHO surveillance list. Results Among 47 patients with recent HIV-1 infection only 1 (2%) had evidence of TDR mutation. No major resistance mutations were found, but the frequency of strains with ≥1 accessory resistance-associated mutations was high, at 98%. Accessory mutations were present in 11% of reverse transcriptase, 96% of protease, and 27% of gp41 sequences. Mean number of accessory resistance mutations in the reverse transcriptase and protease sequences was higher in viruses with no compensatory mutations in the gp41 HR2 domain than in strains with such mutations (p=0.031). Conclusions Despite the low prevalence of strains with TDR mutations, the frequency of accessory mutations was considerable, which may reflect the history of drug pressure among transmitters or natural viral genetic diversity, and may be relevant for future clinical outcomes. The accumulation of the accessory resistance mutations within the pol gene may restrict the occurrence of compensatory mutations related to enfuvirtide resistance or vice versa.

Treatment of tobacco dependence among HIV-infected patients: rationale and preliminary actions taken in Poland

Tobacco smoking and non-communicable diseases related to tobacco use are currently the most important health challenges in population of HIV positive patients, also in Poland. Treatment of tobacco dependence in HIV-infected individuals is now emerged as one of the most important areas for clinical care. One of the rationale for intensifying smoking cessation efforts in HIV population comes from epidemiological observations suggesting that tobacco smoking is responsible for 7 years of life lost in HIV-infected smokers. The Health Promotion Foundation in collaboration with the HIV specialised medical society in Poland has launched a multi-component programme aimed at reducing the prevalence of tobacco smoking in HIV population at least by half in the next years. The programme involves several activities: (1) research aimed at characterising the smoking epidemic among HIV positive patients in Poland; (2) assessment and capacity building in smoking cessation among healthcare professionals who treat HIV patients; as well as (3) formulation of recommendations for a comprehensive nationwide programme of tobacco dependence treatment in this group of patients in Poland.

A heavily pre-treated HIV positive patient with limited treatment options and multiple concomitant diseases treated successfully with raltegravir – the first case in Poland

Summary We present a case of a heavily antiretrovirally pre-treated 38-year old male patient with numerous concomitant diseases and no or very few treatment options available who was started on raltegravir regimen, as part of early access programme, with optimized background. The patients previous regimes all have finally failed and he accumulated numerous drug mutations. He also had developed a chronic disseminated MAC infection, which probably was responsible for the failure of his antiretroviral therapy. After changing the regimen to raltegravir in March 2008, CD4 cell count rose and HIV viremia became undetectable. Now the patient is still taking the new regimen without any side effects and is in good medical condition. No signs of HIV infection or concomitant diseases progression are present so far.

The role of nevirapine in the antiretroviral therapy

Summary In the presented multicenter study an attempt was made to evaluate the role of nevirapine used in treatment of HIV-seropositive patients in both groups: naive as well as experienced. The therapeutic effect was evaluated while analysing the HIV-RNA level and the increase in CD4 cell count. The reasons for which the new schema with nevirapine was introduced in experienced patients were as well analysed. Among these reasons were mainly side effects of different character. On the basis of the obtained results very good virologic response was reported in both groups, naive and previously treated. Immunologic response in both populations discussed was similar though the initial level of CD4 was two times lower in naive patients in comparison with experienced population.