Abstract: Increased occurrence of sexual dysfunction (SD) among patients treated with highly active antiretroviral therapy (HAART) has been reported. To assess prevalence of self-reported SD and to identify factors related to this alteration with special focus to its relationship with adherence behavior, we conducted an intercohort analysis among HIV-infected persons treated with HAART. In an anonymous questionnaire investigating HAART nonadherence, patients were asked to report the occurrence of dysfunction in sexual activity over the previous 4 weeks. Among 612 participants, 125 (21%) reported some degree of SD. "Moderate"/"severe" alterations were reported in 6% and were independently associated with self-reported worsening of viro-immunological parameters (OR 3.90; 95% CI 1.08-14.18), higher symptom score (OR 1.13; 95% CI 1.05-1.22), and reporting abnormal fat accumulation (OR 4.33; 95% CI 1.55-12.11). Furthermore, nonadherent persons had an increased risk of SD (OR 3.44; 95% CI 1.30-9.08). In conclusion, patients' perceived SD represents a relevant problem for HIV-infected persons treated with antiretrovirals and is strongly associated with suboptimal HAART adherence.
Abstract: OBJECTIVES: To investigate the association between insulin resistance and rapid virologic response. DESIGN: All consecutive HIV/hepatitis C virus coinfected patients who started peg-interferon alpha-2a (180 microg/week) and ribavirin 1000-1200 mg/day were analysed. METHODS: Insulin resistance was defined according to the homeostasis model of assessment-insulin resistance calculated as fasting insulin (mIU/l) x fasting glucose (mmol/l)/22.5. Rapid virologic response was defined as testing negative for hepatitis C virus-RNA after 4 weeks of therapy. Fasting levels of insulin and glucose in plasma were measured in all patients on the first day of treatment. Hepatitis C virus-RNA was determined by quantitative PCR assay (version 3.0). Hepatitis C virus-RNA was measured by qualitative PCR assay (COBAS 2.0) after 4 weeks of treatment. RESULTS: Seventy-four HIV/hepatitis C virus coinfected patients were enrolled [mean age 41.7 years (SD 5.3), 61 men, 54.1% with advanced fibrosis (F3-4 according to METAVIR classification), 52.4% with infection by hepatitis C virus genotype 1 or 4]. Rapid virologic response was reached by 30 subjects. In the multivariate analysis the independent predictors of rapid virologic response were: genotype 1 or 4 [adjusted odds ratio 0.18 (0.06-0.55)], hepatitis C virus-RNA < 400.000 UI/ml [adjusted odds ratio 0.229 (0.09-0.92)] and homeostasis model of assessment-insulin resistance more than 3.00 [adjusted odds ratio 0.1 (0.05-0.6)]. CONCLUSION: The homeostasis model of assessment-insulin resistance score should be evaluated and possibly corrected before starting anti-hepatitis C virus therapy.
Abstract: Hepatitis C virus-related long-term complications are nowadays a leading cause of morbidity and mortality in HIV-infected persons. According to international guidelines, all HIV/HCV-coinfected patients should be evaluated and, if eligible, treated with pegylated interferon plus ribavirin. The management of anti-HCV treatment side effects, which may be even more serious in HIV patients, is very important to minimize treatment early discontinuations. The purpose of this review is to supply clinicians with an update, provided by the most recent and relevant literature, of underlying mechanisms, incidence, and advice about the management of pegylated interferon and ribavirin side effects in HCV/HIV-coinfected patients.
Abstract: We evaluated the efficacy of tenofovir (TDF) - and didanosine (ddI)-containing backbones in HIV-infected experienced subjects. We included in the study 245 subjects who started a TDF/ddI-containing HAART with HIV-RNA > 3 log(10) cp/ml and an available genotypic resistance test at baseline. At baseline, median CD4 counts and HIV-RNA were 278 cell/mmc and 4.32 log(10) cp/ml, respectively. Seventy-four subjects (30.2%) discontinued TDF and/or ddI, 23 of them for drug-related toxicities or intolerance. One-hundred and twenty-six (51.4%) subjects achieved virologic success (HIV-RNA < 50 copies/ml in two consecutive determinations) in a median time of 6.1 months; higher HIV-RNA levels (HR: 0.66, 95% CI: 0.54- 0.79, p < 0.001 for each additional log(10) copies/ml), and the total number of mutations either for PI and NNRTI at baseline (HR: 0.87, 95% CI: 0.81-0.92, p < 0.001 for each additional mutation) were both predictors of virologic success. M184V was marginally associated with virologic success (HR: 1.34, 95% CI: 0.94-1.90, p = 0.10 vs no M184V), whilst the number of TAMs was not associated. One-hundred-thirty-three (54.3%) subjects achieved immunologic success (increase of > or = 100 cells/mm(3) from baseline) in a median time of 7.5 months; immunologic success was associated with HIV-RNA levels at baseline (HR: 0.91, 95% CI: 0.79-0.98, p = 0.04 for each additional log(10) copies/ml), the total number of mutations either for PI or NNRTI (HR: 0.91, 95% CI: 0.85-0.98, p = 0.01 for each additional mutation) and CD4 count at baseline (HR: 1.11, 95% CI: 1.00-1.23, p = 0.05 for each additional 100 cells/mm(3)). Results obtained by the on-treatment analyses were comparable. In our study, HAART containing TDF/ddI seem associated with a virologic and immunologic response, when such regimens are chosen according to a genotypic resistance test.
Abstract: OBJECTIVES: To evaluate antiviral efficacy of stavudine/tenofovir (d4T/TDF) backbone combination in late-line antiretroviral therapy, and to assess clinical and virological determinants of treatment success. DESIGN: Multicentric retrospective analysis on patients starting d4T/TDF after highly active antiretroviral therapy (HAART) failure. METHODS: The primary endpoint was the change in plasma HIV-1 RNA from the baseline (time of d4T/TDF initiation) to 6 months of therapy; secondary endpoint was the risk of virological failure. RESULTS: Among 172 patients included, a mean change in HIV-1 RNA of -1.69 (+1.23) and -1.53 (+1.43) log10 cp/ml was observed respectively at weeks 24 and 48 after starting d4T/TDF combination. Any single type-1 thymidine analogue mutation (TAM; M41L, L210W, T215Y) had a negative effort on the change in HIV RNA at 6 months, whereas among type-2 TAMs (D67N, K70R, K219Q), only D67N showed a trend for a negative effect. Presence of M184V mutation was related with a greater reduction in HIV RNA during d4T/TDF exposure. The risk of virological failure at 6 months after d4T/TDF starting was 22%. Type-1 TAMs were associated with a greater risk of failure (adjusted hazard ratio [HR]=1.65; 95% confidence interval [CI] 1.19-2.29). Conversely, M184V showed a protective effect. In 17 genotypic tests available at failure, no K65R mutation was detected, whereas a trend for an increasing prevalence of d4T-associated mutations was found. CONCLUSIONS: Combining TDF with a thymidine analogue as d4T may be effective as component of antiretroviral rescue regimens in HIV-infected patients with previous exposure to nucleoside analogue reverse transcriptase inhibitor. Previous selection of type-1 TAMs induces a detrimental effect over virological response.
Abstract: OBJECTIVES: To compare the characteristics of HIV-infected subjects who had ever used with those who had never used Complementary and Alternative Medicine (CAM). DESIGN: The European Level Epidemiology of Complementary Therapies in HIV project (ELECTHIV 2), a case-control study, was conducted in seven European countries. All HIV-infected subjects who consecutively attended the offices of the collaborating organizations were eligible for this study. Information was obtained from self-administered, anonymous questionnaires. SETTING: A total of 1066 subjects entered the study: 632 were CAM users and 434 had never used CAM. RESULTS: CAM use was more common among females than males (odds ratio (OR) 1.6; 95% confidence interval (CI) 1.2-2.2) and in more educated subjects. CAM use was less common among subjects taking highly active antiretroviral therapy (HAART) (OR 0.5; 95% CI 0.3-0.8), but was more common in outpatients who reported HAART-related side effects (specifically neuropathy). CONCLUSION: This study indicates that CAM use in HIV-infected subjects is related to female gender, higher levels of education and longer duration of HIV infection.
Abstract: BACKGROUND: One of the more vigorous debates in the field of highly active antiretroviral therapy (HAART) is how to start it and what the optimal drug sequence is. METHODS: A retrospective cohort analysis was performed. The aim was to evaluate which variables could influence the virological response to second-line genotypic-based HAART in patients with virological documented first-line HAART failure. A positive response was defined as a confirmed HIV RNA level < 50 copies/ml. RESULTS: Two hundred and eight patients were included. Demographic characteristics, risk factors for HIV acquisition, and drugs included in the initial treatment did not significantly influence the considered outcome. According to a multiple logistic model, the presence of thymidine analogue mutations (TAMs) had a negative association with the virological outcome (P = 0.006), whereas the use of a boosted protease inhibitor (PI) in second-line HAART was positively associated with the endpoint (P = 0.001). Patients receiving a genotypic-based second-line HAART containing a boosted PI achieved a viral load < 50 copies/ml in a 74.2% of cases compared with 52.2% of those whose therapy did not contain a boosted PI. This difference was statistically significant (P = 0.002) with an odds ratio (OR) of 2.63 and a 95% confidence interval (CI) ranging from 1.46 to 4.76. This last variable positively influenced the outcome even when the analysis was restricted to patients harbouring a virus presenting TAMs. In this case, second-line HAART was successful in 66.7% of cases with an OR of 3.25 and a 95% CI ranging from 1.28 to 8.25 (P = 0.014). CONCLUSIONS: the wider range of available therapeutic options has made resistance and drug-sequencing considerations a crucial point in selecting first-line HAART. Our data indicate that, by limiting the risk of selecting or accumulating TAMs, it could be possible to save further therapeutic options. In second-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of the use of NRTI backbones, which retain only a partial effectiveness.
Abstract: We report a fatal case of malaria in an HIV-coinfected nonimmune traveler. The primary cause of death is discussed. The importance of prevention of malaria in nonimmune travelers is stressed. Prevention of malaria in nonimmune travelers should be regarded as a priority area for clinical practice and operational research.
Abstract: We studied the predictive value of self-reported adherence and plasma drug concentrations on virological rebound to HAART. Among 238 participants in the AdICoNA study who had viral load < or = 500 copies/ml, 42 (17.6%) experienced virological rebound by 96 weeks. Both self-reported non-adherence and sub-optimal concentration were independently associated with a higher risk of virological rebound.
Abstract: This study analysed the level of adherence to anti-HIV therapies in illegal drug users compared to non-users. Out of 214 patients interviewed. 60 (28%) reported current use of one or more illegal drugs (heroin, cocaine), alcohol (>6 U/day), psychoactive drugs and others. Within the two groups reporting use of heroin and cocaine, the percentage of patients achieving good levels of compliance was higher than among patients who reported not using any substance (50 and 46% vs. 42.3%), among the users of psychoactive pharmaceuticals and alcohol the percentage of high-compliant patients tended to be lower (respectively 26.6 and 30%), but the difference was not significant.
Abstract: The aim of this study was to analyse in a large sample of HIV-infected subjects the expectations toward complementary therapies (CT) and the characteristics of users. Self-administered anonymous questionnaires were distributed in seven European countries among HIV-infected subjects consecutively attending the offices of AIDS organizations. Among 632 ever CT users, nutritional supplements (124 subjects) and psycho-physiological approaches (116 subjects) were the most frequent CT used: 61.4% used CT to improve energy. Half the CT users wanted to prevent or alleviate the highly active antiretroviral therapy (HAART) side effects. General malaise and neuropathy were the most common HAART side effects, where CT users found improvement (62.0% and 54.7%, respectively). Acupuncture improved neuropathy in a high proportion of subjects (87.5%); whereas for others CT were considered less effective (range 20.0-36.4%). The most common expectations from CT were to improve energy and to prevent or alleviate the HAART side effects. This suggests that HIV-infected people expect not so much specific help as general support from CT.
Abstract: We evaluated adherence to HIV treatments every 4 months during one year in 63 HIV-infected subjects using combination therapies including a protease inhibitor. A total of 18 subjects reported a high level of adherence, 14 in two evaluations, and eight a low level of adherence in all the three evaluations. The remaining 23 subjects (36.5%) reported different levels of adherence to treatment in the three evaluations. These findings suggest that the level of adherence to treatment changes markedly for each patient over time.
Abstract: This paper reviews the Italian literature and illustrates the results of a survey on Histoplasma capsulatum var. capsulatum infection carried out in the Bergamo area of Italy over the last 10 y. During the period January 1989-July 1999, 7 patients were diagnosed as being affected by the H. capsulatum var. capsulatum infection. Until 1999 41 cases have been described in the Italian literature (9 before the 1980s, 6 in the 1980s and 26 in the 1990s). The epidemiological profile of histoplasmosis is well-defined: risk factors are activities such as visiting caves or building sites, travelling and immigration, and it affects both immunocompetent and patients with AIDS. However, in the past, the Italian soil was considered as a low-endemic pabulum for H. capsulatum var. capsulatum and only a few autochthonous cases of histoplasmosis have been reported in Italy, specifically in the Po valley. In the present series, the identification of new cases in the Po valley in Lombardy suggests the possible autochthonous presence of histoplasmosis in Italy.
Abstract: The authors present the AIDS cases (CDC '93) observed in Brescia from 1983 to 1994. They observed 1189 subjects (M 84%, F 16%) with a mean age of 32.7 years (intra-venous drug users 75.1%, heterosexuals 14%, homosexuals 9.6%). The mean survival observed was 56.7 weeks from the diagnosis of AIDS (mortality per year 78%). The most frequent AIDS-defining events were Visceral Candidiasis, P. carinii Pneumonia (PCP) and Neurotoxoplasmosis, while the longest and shortest mean survival was for Kaposi's Sarcoma (89 weeks) and Wasting Syndrome (8.4). The mean value of CD4+ lymphocyte counts on AIDS diagnosis was 72.6/microl (1166 cases) and the highest and lowest were in non-Hodgkin's Lymphoma (NHL; 147.6/microl) and Cryptosporidiosis (18.8/microl). Antiretroviral therapy had been given for at least a month in 41.4% subjects (mean treatment duration of 74.8 weeks). The Cox model has demonstrated the favourable effect on survival of high CD4+ lymphocyte counts on diagnosis, antiretroviral therapy, the diagnosis of Tuberculosis (TBC) and PCP as initial markers and the diagnosis of TBC, PCP or Cytomegalovirus infection (CMV) during the entire clinical evolution. Moreover, the unfavourable effect of high age, diagnosis of Progressive Multifocal Leucoencephalopathy (PML), Wasting Syndrome and NHL as initial markers and diagnosis of PML or NHL in any moment of the disease has been demonstrated.
Abstract: Background: Histoplasmosis is a fungal disease with a worldwide distribution. Travelers returning from endemic areas with a history of exposure to fungal spores have a high risk of infection. Methods: We report four cases of acute pulmonary disease in Italian spelunkers returning from Mato Grosso, Peru. Results: Symptoms and radiologic findings were consistent with acute pulmonary illness. Laboratory data supported the hypothesis of histoplasmosis. Conclusions: Histoplasmosis should be considered in the differential diagnosis in travelers returning from endemic areas, who report a risk of exposure, and present with respiratory illness. In this setting, seroconversion may be considered diagnostic of pulmonary histoplasmosis.
