Primary syphilis in HIV-negative patients is on the rise in Greece: epidemiological data for the period 2005-2012 from a tertiary referral centre in Athens, Greece.

BACKGROUND: Epidemiological data on primary syphilis in Greece are limited. OBJECTIVE: The purpose of the present study was to investigate the trends of the disease in Greece during the last few years and whether they are in accordance with the trends in other European countries and the United States of America. METHODS: We conducted a retrospective analysis based on records of patients who visited the Sexually Transmitted Infections Unit of 'A. Sygros' Hospital in Athens, Greece, during the period 2005-2012. Our hospital is a tertiary referral centre for sexually transmitted infections covering an area of more than four million people, which is almost half the population of Greece. We documented the total annual number of patients, the male to female ratio, sexual orientation, patients' ethnic origin and education level. RESULTS: We reviewed the records of 1185 patients with a confirmed diagnosis of primary syphilis. The total number of patients with primary syphilis has risen from 111 in 2005 to 158 in 2012, an increase of 42.3%. The mean annual number is 148. The mean male to female ratio is 4.76 : 1, with a peak value of 8.50 : 1 in 2011. The majority of patients are of Greek origin, ranging from 67.4% to 87.2%. Within the male patients group, it seems that the percentage of men having sex with men has risen steadily from 2005 (20.7%) up to 2010 (59.1%) with a decline in 2012 (46.0%). The mean value over 8 years is 45.0%. CONCLUSION: Primary syphilis in Greece is on the rise. Τhe majority of our patients are Greek, despite immigrant influx. Men clearly outnumber women, representing more than 80% of the total number of patients. Furthermore, there seems to be a trend towards predominance of men having sex with men as the core group among male patients.

A short, 8-week course of imiquimod 5% cream versus podophyllotoxin in the treatment of anogenital warts: A retrospective comparative cohort study.

BACKGROUND: Studies comparing head-to-head treatment modalities for anogenital warts are lacking. AIM: We sought to compare a short, 8-week course of imiquimod 5% cream to versus the standard 4 week course of podophyllotoxin in the treatment of anogenital warts and to assess factors that may affect response to treatment. METHODS: This was a retrospective cohort study. We reviewed medical files of otherwise healthy patients with a first episode of anogenital warts who were treated with either a short, 8-week course of imiquimod or the standard 4-week course of podophyllotoxin. Inverse probability of treatment weighted (IPTW). Logistic regression was employed to evaluate factors that may affect response to therapy. RESULTS: The study included 347 patients. In patients with lesions on dry, keratinized anatomical sites, the complete clearance rates were 7.6% for imiquimod and 27.9% for podophyllotoxin (P < 0.001). In patients with lesions on moist, partially keratinized sites, no difference between the treatments was revealed. Significant predictors of > 50% reduction in wart area were location of lesions [odds ratio (OR) (95% confidence interval (CI)): 3.6 (1.84-7.08), P = 0.0002] for "partially keratinized" versus "keratinized" sites and treatment used [OR (95% CI): 1.79 (1.08-2.97), P = 0.024] for podophyllotoxin versus imiquimod. LIMITATIONS: The retrospective design of the study was a limitation that we mitigated against with the use of IPTW logistic regression. CONCLUSION: A standard 4 week course of Podophyllotoxin was more effective than an 8-week course of imiquimod only for lesions on keratinized sites. Treatment with podophyllotoxin and location of lesions on partially keratinized sites were independent predictors of >50% reduction in wart area.

Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions.

BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. METHODS: HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. RESULTS: The proportion of sequences with SDRMs was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. CONCLUSIONS: The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients.

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

The prevalence of HIV-1 drug resistance mutations in naïve 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--August 2003, 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 all 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% CI: 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-1 transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%.

Mutations associated with genotypic resistance to antiretroviral therapy in treatment naïve HIV-1 infected patients in Greece.

The widespread use of antiviral drugs against HIV has increased the prevalence of HIV-1 resistant strains among naïve individuals due to transmission of resistant strains. The purpose of this study was to investigate the presence of HIV-1 strains harboring resistance mutations in naïve patients in Greece. Blood samples were collected from 25 individuals. The DNA sequence of protease and partial reverse transcriptase regions (codons 41-223) were obtained by direct sequencing. Our results showed the absence of any primary resistance mutations in the study population. However, we were able to identify high prevalence of sequence polymorphisms at positions in reverse transcriptase region associated mainly with resistance to NNRTIs. Moreover, in protease region several secondary mutations were detected, suggesting the higher genetic variability of this region. The clinical significance of the polymorphisms associated with reduced susceptibility to NNRTIs remains to be clarified.

Molecular characterization of a recombinant HIV type 1 isolate (A/G/E/?): unidentified regions may be derived from parental subtype E sequences.

Recombination is one of several factors contributing to the genetic diversity of HIV-1, which is divided into group M (itself comprising 11 subtypes, A-K) and two other groups named O and N. In the present study, the full-length genome of an HIV-1 isolate obtained from a Greek subject (GR17) infected in the Democratic Republic of the Congo (formerly Zaire) was analyzed to reveal a novel mosaic sequence composed of subtypes A, G, and E and regions of indeterminate classification. In particular, most of pol and tat/vpu, as well as the region encoding intracellular domain of gp41, did not cluster with any of the previously characterized HIV-1 subtypes. The clustering of the LTR of GR17 with subtype E was suggestive of a subtype E origin of the unclassified regions. However, the identification of distinct characteristics in the LTR, such as two functional NF-kappaB sites and a distinct TAR element, compared with those of circulating (A/E) recombinants, suggests that the partial subtype E sequences found in GR17 and the mosaic viruses (A/E) have not derived from each other. These results provide evidence that parental subtype E may have existed in the geographic area of Central Africa.

Genotypic characterization of human immunodeficiency virus type 1 in Greece. Multicentre Study on HIV-1 Heterogeneity.

The HIV-1 subtype distribution in 83 HIV-1-seropositive individuals living in Greece was investigated by using the heteroduplex mobility assay (HMA), DNA sequencing, and phylogenetic analysis. The results revealed that partial HIV-1 gp120 sequences from 71 (86%) patients were subtype B, 5 (6%) were subtype A, 4 were subtype D (5%), 2 (2%) were subtype C, and 1 (1%) was subtype I. The subtype I isolate was documented in an intravenous drug user. A high prevalence (90-100%) of B isolates among intravenous drug users, hemophiliacs, and homosexual men was observed, in contrast to heterosexuals, among whom non-B subtypes seemed to be common (42.9%, p < 0.001). Among the Greek population subtype B is the most frequent (94%), in contrast to the high prevalence (57%) of non-B isolates found in emigrants living in Greece (p < 0.001). A heterosexual transmission case of subtype D in a Greek individual not traveling abroad was also documented. The broad HIV-1 diversity in Greece may be explained by population movements, such as migration and traveling.

Virological and immunological response to HAART therapy in a community-based cohort of HIV-1-positive individuals.

PURPOSE: To determine virological and immunological response to highly active antiretroviral therapy (HAART) and to investigate factors influencing response in a community-based setting. METHOD: Plasma HIV RNA levels and CD4 cell counts were studied in 168 unselected individuals starting HAART including indinavir or ritonavir or hard-gel saquinavir-containing regimens. RESULTS: Overall, 60% of the patients reduced their HIV RNA to below 500 Eq/mL, but half of them experienced a subsequent virologic rebound. Patients with higher baseline HIV RNA, higher baseline CD4 cell count, and simultaneous initiation of combination therapy and patients on indinavir or ritonavir regimen were more likely to have virologic response within 6 months since HAART initiation. Patients with lower baseline CD4 cell count and with lower rates of viral clearance had a higher probability of a subsequent virologic rebound. Forty percent of the patients had increased their CD4 cell counts by more than 100 cells/microL (immunologic response). The probability of immunologic response was independent of baseline HIV RNA levels and CD4 cell count; however, the more complete the virologic suppression, the higher the probability of immunologic response. Thirty percent of the patients had discordance between virologic and immunologic responses. CONCLUSION: The rate of virologic failure in this unselected group of patients was higher than that observed in randomized clinical trials, but only a minority (11%) of the patients were treatment naïve. Starting combination therapy simultaneously and initiating antiretroviral therapy before advanced HIV disease has developed predict virologic response, whereas the magnitude of viral suppression predicts mid to long immunological response.

Lack of reactivation of cytomegalovirus retinitis in an AIDS patient, during and after stopping long-term cidofovir treatment: case report.

The case of an AIDS patient with cytomegalovirus (CMV) retinitis who was treated with cidofovir for 17 consecutive months, without any adverse effect, is presented. In the context of antiretroviral therapy, cidofovir therapeutic regimen was 5 mg/kg of body weight for 2 weeks and 5 mg/kg thereafter every other week. Probenecid, hydration and monitoring for proteinuria were also used to prevent nephrotoxicity. The patient stopped maintenance therapy for CMV retinitis after the permanent rise of CD4+ cells above 100 c/mm3. For more than 10 months after drug withdrawal the patient remains free of retinitis.

Experience with adriamycin, bleomycin, vincristine (ABV) palliative chemotherapy in advanced AIDS-related Kaposi's sarcoma.

After administration of Adriamycin, bleomycin, vincristine (ABV) as palliative chemotherapy in advanced AIDS-related Kaposi's sarcoma (AIDS.KS) patients with low Karnosfsky performance scores, the authors attempted to estimate the overall biological cost/benefit relating to the disease. The authors analyzed data from 20 consecutive AIDS patients with advanced Kaposi's sarcoma presenting skin and visceral involvement treated with ABV every 3 weeks. An increased rate of infections, HIV and ABV-related side effects was observed. The performance amelioration (about 30%) was not significantly correlated with AIDS.KS clinical remission. CD4 count at baseline (p < 0.05), ABV therapy duration (p < 0.001), the achieved AIDS.KS clinical amelioration score (p < 0.01) and the improved Karnofsky score (p < 0.001) were significant predictors of life expectancy which was unrelated to the rate of side effects. The authors conclude that ABV palliative chemotherapy can assist in protracting life expectancy and improving the Karnofsky score.

Hospital care for persons with AIDS in the European Union.

This study estimates the current and future hospital resources for AIDS patients in the European Union (EU), using multinational scenario analysis (EU Concerted Action BMH1-CT-941723). In collaboration with another EU-project ('Managing the Costs of HIV Infection'), six national European studies on the utilization of hospital care for AIDS have been selected to provide the data for our analysis. The selection criteria involve recentness, quality, comparability, accessibility and representativeness. Baseline hospital resource utilization is estimated for hospital inpatient days and outpatient contracts, using a standardized approach controlling for two severity stages of AIDS (chronic stage and late stage). The epidemiological part of the study is based on standard models for backcalculating HIV incidence and projecting AIDS incidence, prevalence and mortality. In the next step, baseline resource utilization is linked to epidemiological information in a mixed prevalence and mortality-based approach. Several scenarios render different future epidemiological developments and hospital resource needs. For the year 1999, hospital bed needs of 10,000-12,700 in the EU are indicated, representing an increase of 20-60% compared to the estimated current (1995) level. The projected range for 1999 corresponds to a maximum of 0.65% of all hospital beds available in the EU. The growth in the number of outpatient hospital contacts is projected to possibly exceed that of inpatient days up to 1.82 million in 1999. Our methodology illustrates that estimation of current and future hospital care for AIDS has to be controlled for severity stages, to prevent biases. Further application of the multinational approach is demonstrated through a 'what-if' analysis of the potential impact of combination triple therapy for HIV/AIDS. Estimation of the economic impact of other diseases could as well benefit from the severity-stages approach.

Immune response to hepatitis A vaccination in HIV-infected men in Greece.

HIV-infected patients are at increased risk for acquiring hepatitis A virus (HAV) infection. We evaluated the seroconversion rate (anti-HAV antibodies ≥ 20 mIU/ml) and the geometric mean antibody titres (GMTs) in a group of 351 HIV infected men, who had received two doses of a hepatitis A vaccine. We analysed blood samples collected at one, six, 12 and 18 months following the administration of the second dose of the vaccine. The seroconversion rate one month after the second dose of the vaccine was 74.4% (260/351). At month 18 after the end of vaccination, 56.1% of the subjects remained seropositive. GMTs were 315, 203, 153 and 126 mIU/ml at months 1, 6, 12, and 18, respectively. Logistic regression revealed that the CD4 count is the only factor affecting response to vaccination (P = 0.019). A higher response rate and higher GMTs were observed in patients with CD4 counts ≥ 500 cells/mm(3) (76.6%) than in patients with CD4 counts 200-499 cells/mm(3). In conclusion, even in patients with near-normal CD4 counts, the response to the hepatitis A vaccine is impaired.

Re-evaluation of the natural course of bullous pemphigoid. A prospective study.

BACKGROUND: Few studies of prospectively collected data regarding the natural course of bullous pemphigoid have been performed. METHODS: The following factors were combined both quantitatively and qualitatively to obtain results: gender, clinical activity based on the estimation of the body area involvement, disease duration, relapses, coexistence with other disease states, and serology Twenty-seven consecutive patients were followed up for 1 year. RESULTS: Most disease activity (85.2%) is exhibited in the first year after onset. There is a lack of parameters with clear predictive significance. The extent and severity of skin involvement are equally distributed between the sexes and not affected by the disease duration. The generalized form of the disease is predominant (86.5%). The average clinical activity in relapses within the year of follow-up is 48% of the initially observed attack. The probability for recurrence is higher in seropositive patients (overall 37%). Coexistence with other disease states seems to be a random chance event. CONCLUSIONS: The lack of parameters with predictive importance underlines the necessity of a thorough follow-up to prevent treatment-related complications in elderly patients.

The impact of new antiretroic therapeutic schemes on the cost for AIDS treatment in Greece.

The paper attempts to evaluate the clinical and economic benefits between the administration of the dual and triple antiretroic schemes for the treatment of the HIV disease. Clinical and economic data are derived from patients hospitalized in 1996 and 1997 at the University Department of Dermatology and Venereology of Andreas Sygros Hospital. Methodology is based on the comparison of patients' nosological profile and direct annual cost before and after the administration of the triple treatment. The results of the study present that the triple combination therapy yields superior health outcomes, (decrease in the days of hospitalization and in the opportunistic disease events as well as fewer deaths and loss of production). Cost comparison presents a small decrease in the annual patient's cost, where all cost components are diminished, except the medication cost. A substitution of hospital care by drug therapy is revealed and a great change is taken place in the composition of the drugs' cost. Patient cost for antiretroic drugs has more than doubled from 1996 to 1997.