Meeting the WHO 90% target: antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics.

INTRODUCTION: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. M: ethods Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients' characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. RESULTS: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01-2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08-2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04-2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29-2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01-4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52-5.26), p = 0.001]. CONCLUSIONS: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions.

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.

Distribution and time trends of HIV-1 variants in Poland: Characteristics of non-B clades and recombinant viruses.

The spread of HIV-1 subtypes varies considerably both worldwide and within Europe, with non-B variants commonly found across various exposure groups. This study aimed to analyse the distribution and temporal trends in HIV-1 subtype variability across Poland. For analysis of the subtype distribution, 1219 partial pol sequences obtained from patients followed up in 9 of 17 Polish HIV treatment centres were used. Subtyping was inferred using the maximum likelihood method; recombination was assessed using the bootscanning and jumping profile hidden Markov model methods. Subtype B dominated in the studied group (n=1059, 86.9%); in 160 (13.1%) sequences, non-B variants were present [A1 (n=63, 5.2%), D (n=43, 3.5%), C (n=22, 1.8%), and F1 (n=2, 0.2%)]. In 25 (2.1%) cases circulating recombinant forms (CRFs) were found. Five A1 variants (0.4%) were unique AB recombinant forms (URF) not previously identified in Poland. Non-B clades were notably more common among females (n=73, 45.6%, p<0.001) and heterosexual individuals (n=103, 66.5%, p<0.001) and less frequent among men who have sex with men (MSM) (n=27, 17.42%, p<0.001). HIV-1 viral load at diagnosis was higher among non-B cases [median: 5.0 (IQR: 4.4-5.6)] vs. [median: 4.8 (IQR: 4.3-5.4) log copies/ml for subtype B (p<0.001)] with a lower CD4(+) lymphocyte count at baseline [median: 248 (IQR: 75-503) for non-B vs. median: 320 (IQR: 125-497) cells/µl for subtype B; p<0.001]. The frequency of the non-B subtypes proved stable from 2008 (11.5%) to 2014 (8.0%) [OR: 0.95 (95% CI: 0.84-1.07), p=0.4], with no temporal differences for exposure groups, gender, age and AIDS. Despite the predominance of subtype B, the variability of HIV in Poland is notable; both CRFs and URFs are present in the analysed population. Non-B variants are associated with heterosexual transmission, more advanced HIV disease and have stable temporal frequencies.

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.

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

INTRODUCTION: 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. MATERIALS AND METHODS: Partial pol sequences from 833 antiretroviral treatment-naive individuals of European descent (Polish origin) linked to care in 9 of 17 Polish HIV treatment centres were analyzed. Drug resistance interpretation was performed according to WHO surveillance recommendations, subtyping with REGA genotyping 2.0 tool. Time trends were examined for the frequency of t-DRM across subtypes and transmission groups using logistic regression (R statistical platform, v. 3.1.0). RESULTS: Frequency of tDRM proved stable over time, with mutation frequency change from 11.3% in 2008 to 8.3% in 2013 [OR: 0.91 (95% CI 0.80-1,05), p=0.202] (Figure 1a). Also, no significant differences over time were noted for the subtype B (decrease from 8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.79-1.11), p=0.45] and across non-B variants [change from 22.6% 2008 to 23.1% in 2013, OR: 0.94 (95% CI 0.75-1.19), p=0.62]. When patient groups were stratified according to transmission route, in MSM there was a trend for a NNRTI t-DRM decrease (from 6.8% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34-1.02), p=0.0655, slope -0.74%/year) (Figure 1b), related to the subtype B infected MSM (decrease from 7% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34-1.03), p=0.0662, slope -0.75%/year). Overall tDRM frequency decrease was also noted for the heterosexually infected patients [from 17.6% 2008 to 10.3% in 2013, OR: 0.83 (95% CI 0.67-1.02, p=0.077, slope -2.041%/year)] but did not associate with drug class (Figure 1c). In IDUs, the trends in t-DRM frequency were not significant over time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24 (95% CI 0.73-2.26), p=0.4)]. CONCLUSIONS: The frequency of t-DRM in Poland is generally stable over time. Decrease in the overall tDRM frequency in heterosexual infected cases and NNRTI resistance in subtype B infected MSM may be related to the higher treatment efficacy of current cART.

Human meningitis caused by Streptococcus suis.

Streptococcus suis is an important swine pathogen worldwide, which can be transmitted to human beings by direct contact; therefore, S. suis infections occur mainly in people who handle pigs or pork. We present a case of a patient with S. suis meningitis who worked as a butcher in a meat processing plant for 5 years. The 35-year-old man was admitted to the Department of Infectious Diseases in T. Browicz Memorial Central Infectious Disease and Observation Hospital in Bydgoszcz, Poland, with suspected bacterial meningitis. According to his medical history, the patient had been injured during the processing of pork. A microbiological examination of the cerebrospinal fluid and blood revealed S. suis as a single aetiological factor of this infection. The patient was empirically administered cefotaxime (2.0 g at 8-h intervals) and penicillin (9 million U at 8-h intervals). The patient made a complete recovery and his inflammatory markers normalized. Only the hearing deficit of his right ear did not disappear. An otolaryngologist recommended a 4-week steroid therapy. The patient was not examined because he did not report to the clinic. To our knowledge this is the first described case of human meningitis caused by S. suis in Poland.

[HIV preexposure prophylaxis]. / Profilaktyka przedekspozycyjna (PrEP) zakazenia HIV.

The pre-exposure chemoprophylaxis (PrEP) is an experimental approach to HIV prevention. The use of antiretroviral drugs has been shown to be effective in prevention HSIV infection in animals. The results from ongoing clinical PrEP trials have demonstrated that antiretrovirals were able to reduce HIV incidence in women and men. The CAPRISA-004 study demonstrated that 1% TDF gel applied intravaginally decreased the risk of HIV infection among heterosexual women in South Africa. The largest global trial iPr Ex conducted in men who have sex with men (MSM), has demonstrated that chemoprophylaxis with daily oral TDF/FTC was 44% effective in protecting against HIV transmission. Following the results of the iPrEx study, the US CDC issued the interim guidance regarding the use of oral PrEP among MSM. Currently more then 20.000 people will be enrolled in studies with oral or topical antiretroviral agents as pre-exposure chemoprophylaxis.

[Tuberculosis among HIV infected patients]. / Gruzlica w grupie pacjentów zakazonych HIV.

The aim of study was to determine clinical presentation and outcome of tuberculosis among patients infected with human immunodeficiency virus type 1 (HIV-1). During 2001-2006, 36 cases of tuberculosis (TB) was recognized in 33 patients infected with HIV. The majority of patients were men infected with HIV in through intravenous drug using and had a CD4 cell count <200cells/microl at the time of TB diagnosis. The most frequent form of TB was pulmonary localization and lymphadenitis as extrapulmonary localization. Meningitis was recognized in two cases. The diagnosis was confirmed by positive culture for mycobacteria and PCR in 34/36 patients. Mycobacterial smears were positive in 2/36 cases, the skin test reaction with nodule >5mm was positive in 60% cases. Immune reconstruction syndrome was recognized in 4 patients.

[HIV infection in women in childbearing age]. / Zakazenie HIV u kobiet w wieku rozrodczym.

HIV infected women compromise about half of all people living with HIV worldwide. Since HIV is frequently sexually transmitted it follows that women who are seropositive are likely to acquire other sexually transmitted diseases. The gynecologic infections led enhance HIV replication and increased transmission of virus. The presence of STD in known to increase of both acquiring and transmitting HIV. The risk of MTCT can be reduced to below 1% by interventions that include antiretroviral prophylaxis given to women during pregnancy and labour and to the infant in the first weeks of life.

[Morphological liver changes of chronic hepatitis C in antiretroviral-naive HIV-infected patients]. / Obraz morfologiczny watroby w przebiegu przewleklego zapalenia watroby typu C u pacjentów zakazonych HIV nieleczonych antyretrowirusowo.

UNLABELLED: The aim of the study was evaluation of morphological exponents of chronic hepatitis C in naive HIV/HCV co-infected patients. MATERIAL AND METHODS: Investigation were performed in 61 patients with chronic hepatitis C, 21 HIV co-infected. HIV-HCV co-infected patients were included to group I. There were 7 females and 14 males (mean age 31.5 years). In group II there were 40 patients with chronic hepatitis C HIV-seronegatives. There were 22 females and 18 males (mean age 40.1 years). In all patients medical history, physical examination, some laboratory tests (ALT activity, HCV viral load) and histological examination of liver biopsy specimens were performed. In patients from group I HIV viral load and CD4 count were assessed. RESULTS: Among HCV infected (group II) higher biochemical activity of the disease and more intense inflammatory changes and fibrosis in the liver were detected. In group HIV/HCV co-infected 2-times higher values of HCV viral load were detected. There were no connections with morphological liver picture and HCV viral load in these patients. There were no connections between the grade of immunodeficiency and advancing of morphological changes in the liver. So grading as staging were similar, independent on lymphocyte CD4 count. CONCLUSION: In the light of performed investigations it was revealed that HIV not accelerate the natural history of chronic hepatitis C. The grade of immunodeficiency measured by CD4 count seems to no influence on advancing of morphological changes in the liver in naive patients.

[Serum IL-2 and sIL-2R concentration in children with chronic hepatitis B]. / Stezenie IL-2 i sIL-2R u dzieci z przewleklym zapaleniem watroby typu B.

UNLABELLED: The aim of the study was evaluation of serum IL-2 and sIL-2R concentration in children with chronic hepatitis B without previous treatment. MATERIAL AND METHODS: Investigations were performed on sera from 27 children, 13 HBsAg and HBeAg positive (group I) and 14 HBsAg positive, HBeAg negative, anti-HBe positive (group II). Serum IL-2 and sIL-2R concentrations were detected with ELISA method. RESULTS: In all examined children serum IL-2 concentrations were decreased. The mean values of sIL-2R in group I was 4,40 (from 1,78 to 15,74) and in group II was 2,60 ( from 1,59 to 4,81) ng/ ml and were statistically significant higher in HBeAg positive children (group I, p < 0.005). The mean ALT activity in this group of children was increased (mean 74 U/I) . The positive correlation between sIL-2R and ALT activity was observed in group I. CONCLUSIONS: In children with chronic hepatitis B a deficiency of Th1 mediated immunological response was observed. HBeAg/anti-HBe seroconversion seems to change the IL-2/sIL-2R balance.

[HIV and HCV infections--clinical implications]. / Zakazenia HIV i HCV--implikacje kliniczne.

Coexisting HIV and HCV infection involves approx. 10 million people in the world. It is most common in drug addicts taking drug injections as well as in haemophiliacs. In the research we have confronted the existing views on natural history progression in hepatitis C in HIV infected, with our own study. The existing recommendations for hepatitis C treatment have also been presented. It was pointed out that there is a possibility of interaction between the drugs applied in the treatment and the antiretrovirus therapy and what is connected with it, the possibility of potentially adverse actions. It was also shown that early treatment of hepatitis C in HIV infected slows down the progress of liver fibrosis, prevents liver failure, improves HA-Art tolerance, increases immunological reconstruction and improves the quality of the patients' lives.