Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection.

OBJECTIVES: To identify variables predictive of nonadherence to highly active antiretroviral therapy (HAART) and to assess whether self-reported symptoms or medication side effects are related to adherence. DESIGN: Cross-sectional multicenter study Adherence Italian Cohort Naive Antiretrovirals [AdICONA] within the Italian Cohort Naive Antiretrovirals (ICONA). METHODS: Participants receiving HAART completed a 16-item self-administered questionnaire to assess nonadherence in the last 3 days as well as the type and intensity of 24 common HIV- and HAART-related symptoms experienced during the last 4 weeks. RESULTS: From May 1999 to March 2000, 358 persons were enrolled: 22% reported nonadherence and were less likely to have HIV RNA <500 copies/ml (odds ratio = 0.51; 95% confidence interval: 0.31-0.85). Frequency of moderate/severe symptoms or medication side effects in nonadherent participants ranged from 3.6% to 30%. On univariate analysis, nausea, anxiety, confusion, vision problems, anorexia, insomnia, taste perversion, and abnormal fat distribution were significantly associated with nonadherence. Nonadherent persons had a higher mean overall symptom score (12.3 +/- 9.2 versus 8.1 +/- 6.6; p <.001) and mean medication side effect score (2.9 +/- 2.7 versus 1.9 +/- 1.9; p <.001) when compared with adherent participants. In the multivariate analysis, nausea ( p =.003); anxiety ( p =.006); younger age ( p =.007); unemployment ( p <.001); not recalling name, color, and timing of drugs ( p =.009); running out of pills between visits ( p =.002); and being too busy ( p =.03) were independently associated with nonadherence in the last 3 days. CONCLUSIONS: In addition to patient characteristics, medication-related variables, and reasons for nonadherence, patient-reported symptoms and medication side effects were significantly associated with adherence to HAART.

[Experience at a branch center of the National HIV Protease Inhibitor Registry]. / L'esperienza di un centro periferico sul registro nazionale degli inibitori delle proteasi di HIV.

In the present study we show our experience as one of the Centers (center 006) of the Italian Index of Protease Inhibitors (PI). In this multicentric, observational study we studied HIV-positive naive patients for antiretroviral therapy with protease inhibitors. From 8/1/97 to 31/1/98 in our department 64 patients were enrolled and followed up through an electronic medical sheet in order to evaluate efficacy, tolerability, toxicity and compliance of treatment with PI. Our results show a reduction in AIDS-related mortality and a decrease in AIDS defining diseases: in particular data show an increase in CNS pathologies in comparison with other opportunistic events. Moreover, in patients non complaints to therapy, the progression of the disease was more frequent. The side effects more frequently observed during PI treatment were hypertrigliceridaemia and lipodystrophy; gynaecomastia and hyperprolactinaemia were even present, perhaps as expression of direct metabolic action of HAART therapy.

[Saquinavir + Zidovudine + Lamivudine in HIV positive naive or not naive patients] / Saquinavir + Zidovudina + Lamivudina in pazienti HIV positivi naive e non.

The aim of the study was to assess the virological/immunological outcome and safety of Saquinavir (SQV), Zidovudine (AZT) and Lamivudine (3TC) therapy in HIV patients. We retrospectively evaluated the charts of 36 HIV patients (male 87% median age 31 yrs, IVDA 72%) who underwent therapy with 5QV (1800 mg/die), AZT (500 mg/die) and 3TC (300 mg/die). 26 (72%) patients were previously on antiviral therapy for at least 16 weeks. No patient ranked in the CDC group. Patients were treated for at least 48 weeks. Hematological indices, changes in CD4+ cell count and plasma HIV-RNA levels were evaluated every 30, 60, and 90 days respectively. At baseline, CD4 cell count and viral load were 230/mcl and 4.55 log respectively for patients previously on therapy and 382/ l and 4.88 log respectively for naive patients. At week 48 the mean CD4+ cell count increase was 70/ l among previously treated and 98/mcl among untreated patients. In respect to the baseline, lower mean HIV-RNA levels were observed at week 12, 24 and 48. No patient showed AIDS-defining events. No patient discontinued therapy due to suspected toxicity. Patients showed a good immunological and virological response, regardless of their previous antiviral treatment. The terapy regimen was safe and well tolerated

[Acute and chronic viral hepatitis in HIV positive patients]. / Le epatiti virali acute e croniche in pazienti HIV positivi.

In this study we evaluated the spreading of HBV, HCV, HDV and HIV among drug user patients. Spreading of hepatotropic viruses resulted high (HBV 84%, HCV 87%, HDV 7%), while spreading of HIV resulted relatively low (18%). During the period considered we did not observe any favourable effect of hepatotropic viruses on the progression of HIV infection, while the chronic evolution of acute viral hepatitis HBV related was high (90%) in HIV+ patients. HIV infection did not determine different histological findings in respect to HIV- patients with chronic hepatitis, HBV or HCV related

Mild pancreatic damage in acute viral hepatitis.

Whether and to what extent the pancreas is involved in acute viral hepatitis is still unclear. In order to address this issue we evaluated serum and urinary amylase and isoamylase levels in 92 patients with acute viral hepatitis of different etiology and in 60 healthy volunteers. Furthermore, pancreatic structure and volume were evaluated by ultrasound scanning. Significant increase in serum and urinary pancreatic isoamylases was found in 12 and 35% of patients, respectively, in the early stage of the disease. Increase in serum pancreatic isoamylases was found only in patients suffering from B and non-A, non-B hepatitis. Ultrasonographic evaluation did not show any change in pancreatic structure and volume. In conclusion, this study suggests that mild pancreatic damage may occur during viral hepatitis.

[Anti-hepatitis B vaccination in Campania. Final observations of a 3-year vaccination campaign, with special reference to infants born to HBsAg-positive mothers]. / La vaccinazione anti-epatite B in Campania. Osservazioni consuntive di 3 anni di campagna vaccinale, con particolare riguardo ai nati da madre HBsAg positiva.

The results obtained at the end of the first three years of a hepatitis B vaccination campaign in Campania, are reported. HEVAC-B and H-B-VAX proved innocuous and efficacious in producing anti-HBs. Newborn babies and children produced anti-HBs more often and with higher titres than adults. Titre 10 mUI/ml of anti-HBs persisted, in the responders for at least 36 months on average. AVH by HBV was observed in two adult non responders. Transplacental or delivery infection was observed in 9.3% of the babies born of HBsAg positive mothers and more often among babies born of HBeAg positive mothers. Infection by HBV was observed in 6.0% of the babies, in 4.0% of the children and in 12.0% of the adults, in spite of the production of anti-HBs. HB-antigenemia, was as a rule transitory, but sometimes fluctuating or persistent. Careful observation during a prolonged follow up is necessary for these subjects.

Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention.

Role of delta infection in the progression to chronicity of acute HBsAg positive hepatitis.

A previous study of 159 consecutive cases of HBsAg+ acute viral hepatitis, observed from the onset of disease and seen between May 1977 and May 1980, revealed a higher frequency of evolution to chronicity in the region of Naples than that reported for other areas. This suggested that environmental factors might influence the chronically rate. We investigated 125 HBsAg+ acute hepatitis cases for whom sera were available: 35 patients who remained HBsAg+ at the two-year control (28 chronic hepatitis and 7 healthy carriers) and 90 who recovered and seroconverted HBsAg---- anti-HBs during follow-up. At the onset of disease, all patients who cleared HBsAg showed IgM anti-HBc positivity and 48 were also HBeAg positive; no patient was anti-delta positive. On the contrary of the 28 chronic cases only 7 were IgM anti-HBc+ (6 under 13 years old), while 21 were IgM anti-HBc- but anti-delta+. This study demonstrates that not all HBsAg+ acute hepatitis cases are due to HBV and that in our area, superinfection by the delta agent is responsible for most cases of chronic HBsAg positive hepatitis.

Effect of immunosuppressive therapy on HBsAg-positive chronic active hepatitis in relation to presence or absence of HBeAg and anti-HBe.

Two hundred and four patients with biopsy-proven HBsAg-positive chronic active hepatitis were treated for at least 2 years with azathioprine, prednisolone or a combination of both, or were untreated. Prevalences of HBeAg, anti-HBe, and anti-HBc were 26, 58, and 100%, respectively. Criteria for improvement or progression of disease were based on clinical, biochemical, and morphologic parameters. Prednisolone therapy and combination therapy did not modify the course of the disease in HBeAg-positive patients; azathioprine therapy may have been deleterious for these patients. Among HBeAg-negative patients, deterioration or death occurred more frequently in those who were untreated than in those who received the combination of azathioprine and prednisolone. Prednisolone therapy was of moderate effect, whereas azathioprine did not influence the outcome.

Treatment of HBsAg-positive chronic active hepatitis with corticosteroids and/or azathioprine. A prospective study.

204 patients with biopsy-proven CAH were observed for at least one year with periodic examinations including a second liver biopsy for each patient. Patients were assigned at random to a group left untreated or treated with either azathioprine 100 mg daily, or prednisolone (Dutimelan 8 15), or prednisolone plus azathioprine 50 mg daily. The outcome, assessed on clinical, biochemical and histological parameters, was correlated to the presence or absence of HBeAg and its antibody. No treatment was effective in HBeAg-positive patients whereas, among anti-HBe-positive patients, those who were treated with the association of steroids and azathioprine more frequently showed improvement and less frequently deteriorated (p less than 0.01) than untreated patients. Thus, HBsAg/anti-HBe-positive patients with CAH may be treated with the combination of these drugs, even though many side-effects may occur and there are frequent relapses after discontinuation of treatment.

[Maternal-fetal transmission of hepatitis B virus. Follow-up study of 21 infants born to HBSAG-positive mothers, and 6 born to HBSAG-negative mothers with anti-HBV antibodies]. / La trasmissione materno-fetale del virus della epatite B (HBV). Osservazione nel tempo di 21 nati da madri HBsAg positive e di 6 nati da madri HBsAg negative con anticorpi anti-HBV.

Vertical transmission of hepatitis B virus (HBV) was studied in 21 mother-infant pairs. A transient HBs-antigenemia was observed in 60% of the 10 children born to HBsAg healthy carrier mothers and 91% of the 11 babies born to mothers with HBsAg-positive CAH. Among the 16 children showing HBs-antigenemia, 3 developed acute viral hepatitis two of whom showed progression to chronicity.

Serum levels of hepatitis B surface and core antigens during immunosuppressive treatment of HBsAg-positive chronic active hepatitis.

One of the following treatments was randomly assigned to 101 consecutive patients with biopsy-proven chronic active hepatitis: prednisone 20 mg daily, azathioprine 100 mg daily, prednisone 20 mg and azathioprine 50 mg daily, or B vitamins 2 tablets daily (control group). Patients were observed at the beginning of the study, then at 2, 6, and 12 months after treatment. At each visit levels of HBsAg and Dane-particle-associated core-antigen (HBcAg) and their corresponding antibodies were determined. 42 patients were HBcAg positive at the beginning of the study. Of these 42 patients, the 34 who were under treatment remained HBcAg positive and showed a rise in HBcAg titre, while the 8 who were not treated had a fall in HBcAg titre (6 patients) or became HBcAg negative (2 patients) in 6 months. Among 59 patients who were HBcAg negative at the beginning of the study, this antigen became persistently detectable in 40% of the 42 patients who were treated, and was transiently present in 2 (12%) out of the 17 untreated patients (p < 0.05). Our data indicate that long-term prednisone and/or azathioprine treatments favour the replication of hepatitis-B virus in patients with HBsAg-positive chronic active hepatitis.