Acute hepatitis C in persons infected with the human immunodeficiency virus (HIV): the "real-life setting" proves the concept.

OBJECTIVES: Outbreaks of sexually transmitted acute HCV infection have been described recently in several cities in the western world. The epidemic affects mainly MSM who are coinfected with HIV and is supposably linked to certain sexual risk practices. Here, we compared our findings with current knowledge and recommendations. METHODS: HIV-positive patients with the diagnosis of acute HCV infection were included in the retrospective analysis. The patients came from outpatient infectious disease centers in northern German cities. We looked at markers of HIV and HCV infection and compared patients who received treatment and those who did not. Treated patients were followed up to 72 weeks. RESULTS: Three hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C between 2001 and 2008 and were included in the analysis. All patients were male, 315 (99%) patients were of caucasian origin, 296 (93%) declared homosexual contacts as a risk factor for HCV infection, intravenous drug use was declared in 3 (1%) cases. Median age at HCV diagnosis was 40 years (range 20-69 years). Median HCV viral load was 1.2 x 106 IU/mL, 222 patients (70%) had HCV genotype 1, 59 (18%) genotype 4. The median time of HIV infection was 5.5 years (range 0 to 22.4 years). Median HIV viral load was 110 copies/mL (range 25 to 10x106 copies/mL). The median CD 4 count was 461 cells/mm3 (range 55-1331 cells/mm3). Two hundred and fourty-six patients (77%) received anti-HCV treatment, and 175 (55%) had completed therapy by the time of the analysis. Median treatment duration was 33 weeks (IQR 24.1-49.9). 93 of the 175 treated patients (53%) reached a sustained virological response (SVR). In the multivariate analysis, ART at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets were associated with SVR. Treatment duration was significantly higher in the SVR group (40.6 weeks vs 26.6 weeks, p<0.0001). Seventy-three patients (23%) did not receive anti-HCV treatment. In 19 of the untreated patients (26%) the hepatitis C virus was cleared spontaneously. CONCLUSIONS: Our findings confirm that acute hepatitis C in HIV infected patients affects mainly MSM who acquire HCV sexually. Patients had a short duration of HIV infection and a stable immunological situation. In this real-life setting from urban regions in northern Germany, treatment rates appear to be high and effective.

Switch from a ZDV/3TC-based regimen to a completely once daily (QD) regimen of emtricitabine/tenofovir DF fixed dose combination plus a third QD agent (SONETT).

OBJECTIVES: To assess the efficacy and safety of a treatment switch from a twice-daily (BID) regimen containing zidovudine (ZDV) and lamivudine (3TC) plus a third agent to a once daily (QD) regimen containing the fixed-dose combination of tenofovir DF/emtri?citabine (TDF/FTC, Truvada) plus a divergent third QD agent in HIV-1 infected patients. METHODS: Prospective, 48-week, non-randomised, single-group, open-label, study. Fifty-one patients on stable ZDV/3TC-containing HAART, with HIV-1 RNA <50 copies/ml and CD4+ T-cell count >50 cells/microl, were switched to TDF/FTC plus a third agent. Plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts were assessed at baseline and weeks 4, 12, 24, 36 and 48 post-switch. RESULTS: During the 48-week study, 10 patients discontinued prematurely, including three due to adverse events (AEs). At week 48, plasma HIV-1 RNA was <50 copies/ml in 40 patients (78.4%). No patient experienced virological failure (defined as HIV-1 RNA > or =50 copies/ml at two consecutive post-baseline measurements) during the study. Immunologic control was maintained, with no significant changes in CD4+ or CD8+ T-cell counts. A statistically significant improvement from baseline in haemoglobin level was observed at week 48 (median change 0.8 g/dl; p<0.001). There was also a statistically significant decrease in total cholesterol concentration at week 48 (-26.0 mg/dl; p = 0.001) in a subset of patients (n = 22) entering the study with elevated total cholesterol. Treatment was well tolerated and no treatment-related grade 3 or 4 AEs were seen. - CONCLUSIONS: Results from this study support switching from a ZDV/3TC-containing HAART regimen to a completely QD regimen of TDF/FTC plus a third agent. Virologic and immunologic control are maintained, with apparent benefits in haemoglobin.

First-line ritonavir/indinavir 100/800 mg twice daily plus nucleoside reverse transcriptase inhibitors in a German multicentre study: 48-week results.

OBJECTIVES: To evaluate safety and efficacy of the protease inhibitor combination ritonavir/indinavir 100/800 mg twice daily plus 2-3 nucleoside reverse transcriptase inhibitors (NRTI) in antiretroviral-naive patients. METHODS: Within this open-label, uncontrolled multicentre trial, antiretroviral-naive patients (n = 57) with median baseline HIV-RNA of 308,000 copies/mL (range 170-3.01 million copies/mL) and median CD4 cell count of 50 cells/microL (range 0-853 cells/microL) were started on 2-3 NRTIs plus ritonavir/indinavir 100/800 mg twice daily. CD4 cell counts and HIV-RNA were determined at weeks 0, 4, 8, 12, 16, 20, 24 and 48. Statistical analysis was performed on treatment as well as intent-to-treat. RESULTS: Viral load decreased by a median of 3.79 log10 copies/mL (range 2.0-4.60 log10 copies/mL) until week 48. At week 48, 23/57 (40%, intent-to-treat) patients showed a viral load

Treatment of HIV-associated wasting with recombinant human growth hormone: monitoring of body composition changes by bioelectrical impedance analysis (BIA).

INTRODUCTION: Recombinant human growth hormone (r-hGH) has demonstrated efficacy in treating HIV-associated wasting (HAW), however, HAW has become less prominent since the introduction of highly active antiretroviral therapy (HAART). Recent studies suggest that patients receiving HAART may still experience HAW. We investigated the nature of HAW and the efficacy of r-hGH in these patients. METHODS: We treated 27 HIV-positive patients receiving HAART who had either recent loss of >5% body weight or weight <90% lower limit of normal with 12 weeks of r-hGH (6 mg given either daily or every other day). Body composition changes were monitored using bioelectrical impedance analysis (BIA). RESULTS were assessed for all patients and for a subgroup meeting more stringent definitions of wasting (BIA phase angle a<5.6 degrees, n = 14). - RESULTS: Significant increases from baseline in weight and body cell mass (BCM) occurred in the full population (medians: 2.0 kg weight, 1.5 kg BCM). Patients with phase angle alpha<5.6 degrees also showed increases in weight and BCM (medians: 2.5 kg weight, 1.95 kg BCM), and 10 of 14 showed improvements in the ratio of extracellular mass (ECM) to BCM. At follow-up there was a trend towards loss of the weight and BCM gained on treatment. Treatment was well tolerated. CONCLUSION: Patients receiving HAART continue to experience wasting, and respond well to r-hGH therapy as monitored by BIA.

Application of HIV-1 genotypic-resistance testing prevents the evolution of further resistance mutations in heavily pretreated patients.

BACKGROUND: Resistance-associated mutations in HIV-1 evolve even under highly active antiretroviral therapy. OBJECTIVE: To evaluate the clinical efficacy of genotypic-resistance testing (GRT), to estimate the potential of a given antiretroviral therapy for prevention of further resistance mutations. STUDY DESIGN: Ten patients were treated prospectively with drugs, according to the results of a GRT. Five patients were allocated to group I in which antiretroviral therapy could be switched to an effective regimen (consisting of at least three sensitive drugs, from at least two different classes of antiretroviral substances). Five patients (group II) had no option for effective therapy, and continued to be treated non-effectively (at least one applicated substance class only intermediately sensitive, or resistant). GRT and quantitative viral cultures were performed longitudinally for 8 months. Also, plasma HIV-1 RNA, total CD4+ cells, and rates of productively infected CD4+ cells were determined. RESULTS: All the patients in group I showed a significant decrease of HIV-RNA of >1 log/ml (mean, -1.35 log/ml, P=0.025). The mean increase of CD4+ cells was 46 (not significant). The rate of productively infected CD4+ cells decreased significantly (mean, -16 productively infected CD4+ cells per 10(6) total CD4+ cells, P=0.04). In this group no further resistance mutations were detected after 8 months. In group II, none of the patients showed a significant decrease of HIV-1 RNA (mean, +0.05 log/ml), total CD4+ cells decreased (mean, -35, not significant), the rate of productively infected CD4+ cells increased significantly (mean, +124 productively infected CD4+ cells per 10(6) total CD4+ cells, P=0.04), and 4 of 5 patients had additional mutations in the RT gene conferring multi-drug resistance within 8 months (P=0.048). CONCLUSIONS: GRT is predictive of the efficacy of a therapeutic regimen, in particular regarding evolution of further resistance mutations.

A double-blind comparison of itraconazole oral solution and fluconazole capsules for the treatment of oropharyngeal candidiasis in patients with AIDS.

This double-blind trial compared the clinical and mycological efficacy and safety of itraconazole oral solution with those of fluconazole capsules in the treatment of oropharyngeal candidiasis in patients with AIDS. A total of 244 patients were enrolled and randomized to one of three groups for treatment with itraconazole oral solution (100 mg twice daily for 7 days or 100 mg once daily for 14 days) or fluconazole capsules (100 mg once daily for 14 days). Among 194 evaluable cases, complete response (clearance of all symptoms and signs) or marked improvement was noted in 54 of 60 patients (90%) receiving once-daily itraconazole and in 65 of 72 fluconazole-treated patients (90%) at the end of treatment; these results were statistically equivalent (P = .0024). Twice-daily itraconazole produced a clinical response in 51 of 62 patients (82%). The groups were equivalent in terms of early relapse (within the 18-day period studied); 37% of patients in the twice-daily itraconazole group, 35% in the once-daily itraconazole group, and 34% in the fluconazole group relapsed. Drug tolerability was comparable between the three groups. These results show that, in the treatment of oropharyngeal candidiasis, itraconazole oral solution and fluconazole capsules at a 100-mg single daily dose for 14 days are equally effective.

[Secondary prevention of cytomegalovirus retinitis with ganciclovir]. / Zur Sekundärprophylaxe der Zytomegalieretinitis mit Ganciclovir.

The prophylaxis of cytomegalovirus retinitis reactivation is effective in reducing the risk of blindness and in prolonging the remission interval and time of survival if given daily throughout life. In this study, a newly developed therapeutic regimen with 3 infusions a week was compared to the conventional maintenance therapy of 5 infusions a week using the same total weekly dose. For this purpose, ten patients were given 10 mg ganciclovir/kg 3 times a week (group A), and 18 received 6 mg ganciclovir/kg once daily for 5 days a week (group B). Only patients with newly diagnosed retinitis were included in this study. Both groups were comparable regarding their general health and ocular state at the beginning of the study. Induction therapy for stabilization of retinitis had to be given for 17.1 and 16.7 days (P = 0.785). Visual acuity was 0.5 and 0.7, respectively, at the beginning (P = 0.128) and 0.5 each at the end of the study (P = 0.875). Fifty-six percent of both groups presented with central retinal involvement at the beginning, whereas it was 56 and 78%, respectively, at the end (P = 0.250). The retinitis was found to have progressed more than 0.5 papilla diameters (pd) after 63.8 and 64.0 days (P = 0.996) and more than 1 pd after 117.6 and 77.8 days (P = 0.350). New induction therapy had to be performed after 147.9 and 131.5 days, respectively (P = 0.598). The maintenance therapy had to be interrupted due to side effects for 1.4 and 8.3 days, respectively (P = 0.185). According to these results, the prophylaxis of retinitis reactivation with 3 x 10 mg ganciclovir/kg per week is as effective as the established one with 5 x 6 mg/kg per week and can thus be recommended for an improvement in the quality of life for the patients concerned. No problems with this therapy were noted.