Long-term trends in HIV care entry: over 15 years of clinical experience from Poland.

INTRODUCTION: Delay in HIV diagnosis and consequently late care entry with low CD4 counts remain a major challenge for the control of the HIV/AIDS epidemic. The aim of this study was to analyse the evolution of characteristics of the HIV epidemic in Poland. METHODS: Cross-sectional data were collected for 3972 HIV-infected patients followed up in 14 of 17 Polish HIV treatment centres in the years 2000-2015. Clinical data were analysed and factors associated with late presentation (baseline CD4 count < 350 cells/µL or history of AIDS-defining illness) and advanced HIV disease (baseline CD4 count < 200 cells/µL or history of AIDS) were identified. RESULTS: The majority (57.6%) of patients entered care late, while 35.6% presented with advanced HIV disease. The odds of being linked to care late or with advanced HIV disease increased consistently across age categories, increasing from 2.55 [95% confidence interval (CI) 1.46-4.47] for late presentation and 3.13 (95% CI 1.49-6.58) for advanced disease for the 21-30-year-old category to 5.2 (95% CI 1.94-14.04) and 8.15 (95% CI 2.88-23.01), respectively, for individuals > 60 years of age. Increased risks of late entry and advanced HIV disease were also observed for injecting drug users [adjusted odds ratio (aOR) 1.74 (95% CI 1.16-2.60) and 1.55 (95% CI 1.05-2.30), respectively], with lower aOR associated with the men who have sex with men transmission route [aOR 0.3 (95% CI 0.31-0.59) and 0.39 (95% CI 0.29-0.53), respectively]. The frequencies of cases in which patients were linked to care late and with advanced HIV disease decreased over time from 67.6% (2000) to 53.5% (2015) (P < 0.0001) and from 43.5% (2000) to 28.4% (2015) (P = 0.001), respectively. CONCLUSIONS: Despite improvements over time, most patients diagnosed with HIV infection entered care late, with a third presenting with advanced HIV disease. Late care entry remains common among people who inject drugs and heterosexual groups.

Association of chemokine receptor gene variants with HIV-1 genotype predicted tropism.

OBJECTIVES: As a switch from chemokine (C-C motif) receptor 5 [CCR5 (R5)] to chemokine (C-X-C motif) receptor 4 [CXCR4 (X4)] HIV-1 tropism is associated with symptomatic and AIDS stages of infection, while chemokine receptor gene variants modify the tempo of HIV disease progression, we aimed to analyse the association between pretreatment HIV-1 tropism and chemokine polymorphisms known to restrict disease progression. METHODS: V3 genotype tropism prediction was performed in a group of 221 treatment-naïve patients, with subsequent CCR5 Δ32 (rs333), CCR2 V64I (rs1799864), CCR5 promoter (-627 C/T; rs1799988) and CX3CR1 V249I (rs3732378) genotyping performed in 206 patients. Alleles with a protective effect were assigned positive values while risk alleles were assigned negative values to calculate genetic scores. χ(2) tests, Mann-Whitney U-tests and logistic and linear regression models were used for statistical analyses. RESULTS: R5 tropism was found in 85.5% of patients (n = 189) using a false positive rate (FPR) of 5.75% and in 72.8% of patients (n = 161) using an FPR of 10%. A higher frequency of the 5.75% FPR predicted R5 tropism was associated with the CX3CR1 A allele (P = 0.027). Lower additive genetic scores were associated with an increased frequency of 5.75% FPR predicted R5 tropism (P = 0.0059), with the trend confirmed by logistic regression [odds ratio (OR) 0.5819; 95% confidence interval (CI) 0.3457-0.9795; P = 0.0416]. Viral load tended to increase with decreasing genetic score in the logistic regression analysis (slope = -0.127 ± 0.076; P = 0.095; r(2) = 0.161). CONCLUSIONS: The CX3CR1 A allele and lower genetic scores may restrict the switch of HIV-1 tropism from R5 to X4. This effect may be associated with the amount of co-receptor on the cell surface. Chemokine receptor gene polymorphisms influence both disease progression and tropism variability.

Introduction of pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 variant in Polish HIV-infected patients.

OBJECTIVE: Prospective pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 allele can significantly reduce the number of cases of abacavir-related hypersensitivity among HIV-infected patients treated with this drug. The aim of this study was to establish the frequency of the HLA B*5701 variant in HIV-infected Poles. METHODS: The sequence-specific primer (SSP) test was used to assess the feasibility of the introduction of such testing in clinical practice. For this purpose, 234 randomly selected HIV-positive patients were screened using a low-resolution SSP assay, with HLA B*5701-positive results confirmed using a high-resolution test. RESULTS AND CONCLUSIONS: The HLA B*5701 variant was found in 11 of 234 subjects (4.7%). Testing with the selected method proved quick and reliable.

Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection.

Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering on chromosome 3p21. Here the influence of 5 genetic variants was studied: Delta32 CCR5, G(-2459)A CCR5, G190A CCR2, G744A CX3CR1 and C838T CX3CR1. They were screened in a cohort of 168 HIV-1 positive adults [HIV(+) group] and 151 newborns [control group] from northwestern Poland. PCR-RFLP was performed to screen for the variants (except for Delta32 CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for the CCR5 polymorphisms, with the Delta32 allele and the (-2459)A CCR5 allele more frequent among neonates than in the HIV(+) group. No Delta32/Delta32 homozygotes were found in the HIV(+) group, but 16.1 percent were Delta32/wt heterozygotes. In the control group, 1.3 percent; were Delta32/Delta32 homozygotes and 26.0percent were Delta32/wt heterozygotes. Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes containing Delta32 CCR5, 190G CCR2 and 744A CX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and resistance to HIV-1 infection.

Opportunistic infections and other AIDS-defining illnesses in Poland in 2000-2002.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) led to a decreased incidence of the most severe opportunistic infections (OIs) in HIV-infected patients. In Poland, HAART became widely used in 1998. MATERIALS AND METHODS: This study was based on data from medical records data collected in the years 2000-2002 from medical centers for HIV-infected patients in Poland. The aim of the study was to determine the incidence of opportunistic infections (OIs) and other AIDS defining illnesses (ADIs). The chi(2) test was used to determine any significant trends. RESULTS: The incidence of ADIs was 6.8, 6.5 and 4.8/100 persons/year in 2000-2002, respectively. The most common diagnosed OIs were: fungal infections, tuberculosis, recurrent pneumonia, PCP and toxoplasmosis. In patients receiving HAART (HAART+) the incidence of ADIs was significantly lower than in non-ARV-treated as well as in all HIV+ (p < 0.02, p < 0.001, p < 0.001, respectively). A significant decrease in the incidence of ADIs in HAART+ patients between 2000 and 2002 (p < 0.0001) was observed. From 25% to 30% of ADIs among HAART+ patients were diagnosed within the first 3 months of antiretroviral therapy. In HAART+ patients the most common ADIs were fungal infections and tuberculosis. The diagnosis of ADIs resulted in the recognition of HIV status in 8.7-8.9% of patients. CONCLUSIONS: Five years after the introduction of HAART the incidence of ADIs had declined. Fungal infections and tuberculosis were the most common OIs in HIV+ patients in Poland.

[Pneumonia in HIV-infected patients: clinical observations]. / Zapalenie pluc u osób zakazonych HIV--obserwacje kliniczne.

OBJECTIVES: To determine the occurrence of pneumonias in HIV-infected patients in our hospital during 1990-1999; to evaluate the clinical significance of pneumonias in HIV-seropositive patients; to estimate the ethiology of pulmonary infection. MATERIALS AND METHODS: One hundred and two HIV-infected patients, 17 (16.6%) female and 85 (83.3%) male with mean age of 29 +/- 4.5 yrs, were retrospectively analysed. All patients had a physical examination particularly concerning the clinical symptoms of pulmonary infection, X-ray exam and tuberculin skin test (PPD). The stage of HIV infection according to the 1993 CDC classification was determined. All patients had the microbiology test of sputum (Pc, TB, fungi, other pathogen). In some cases the bronchofiberoskopy with bronchoalveolar lavage (BAL) was performed. RESULTS: One hundred and two HIV-positive patients had 129 episodes of pneumonia. We determine the bacterial ethiology in 94/129 (72.9%) cases--TB in 11/129 (8.5%) cases. Fourteen patients had 23 episodes of Pneumocystis carinii pneumonia (PcP). Three patients had CMV--pneumonitis, detected post mortem. In seven cases the ethiology of pulmonary infection was unknown. In summary the ethiology of pneumonia was determined in 58/129 (44.9%) cases. Thirty three patients were died. The pulmonary infections were main cause of death in 23 (67.7%) persons. CONCLUSIONS: In the era of high active antiretroviral therapy (HAART) the pulmonary infections in HIV-positive patients are the main cause of death as before. The PPD test is useless in HIV-positive patients. We make a note the increase cases of TB in HIV-infected patients during the time of observations.

[Natural cytotoxicity of peripheral blood mononuclear cells in Herpes simplex and Varicella-zoster virus infections]. / Naturalna cytotoksycznosc komórek jednojadrzastych krwi obwodowej w zakazeniach wirusami Herpes simplex oraz Varicella-zoster.

Natural cytotoxicity of peripheral blood was assessed in adults with recurrent Herpes labialis and in patients with Herpes zoster. CD16+ cells count, lymphocytes forming conjugates with K 562 cells count and NK activity in chromium-release assay were measured. Decreased CD16+ cells count and depressed NK activity were found during latency of HSV infection. During reactivation of the infection lymphocytes forming conjugates count was increased. Functional activation of natural killing was noted in patients with herpes zoster in the acute phase of the disease. However, no differences between results of all NK tests after herpes zoster versus control group were found.

[Intracranial tumors simulating neurological infections]. / Guzy wewnatrzczaszkowe imitujace neuroinfekcje.

The clinical manifestations were analysed in 16 patients with expanding intracranial lesions hospitalized in the period from Jan 1 1980 to Aug 31 1990. They had been admitted to hospital with the diagnosis of suspected neuroinfection. The initial manifestations and abnormalities in neurological examination might have suggested inflammatory processes in the central nervous system. Only further diagnostic procedures, especially emergency ones such as angiography and CT of the brain made possible establishing of final diagnosis and qualifying the patient for surgical intervention. The authors stress that expanding intracranial lesions should be always taken into account in patients with clinical and CSF abnormalities persisting despite ruling out of neuroinfection.

[Clinical types of herpes zoster in clinical observations 1985-1989]. / Postacie kliniczne pólpasca w obserwacjach klinicznych w latach 1985-1989.

The clinical types of herpes zoster in 286 patients were observed. The differences in the course of disease in persons with and without decreased immunity are described. Some of the neurological complications depending on the localization of the herpes zoster are presented.