Firouzé Bani-Sadr

Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy.

Objective:To evaluate the incidence, clinical features, and risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. Methods:All cases of symptomatic mitochondrial toxicity reported in 416 patients participating in an open, randomized trial of peg-interferon α-2b plus ribavirin vs. interferon α-2b plus ribavirin for 48 weeks were reviewed. Associations with antiretroviral treatments and with clinical and laboratory findings were sought by univariate and multivariate analysis. Results:Eleven of the 383 patients who received at least 1 dose of anti-HCV treatment developed symptomatic mitochondrial toxicity (symptomatic hyperlactatemia and pancreatitis in 6 and 5 patients, respectively). All cases occurred in patients being treated for HIV infection, and the incidence of symptomatic mitochondrial toxicity was 47.5 per 1000 patient-years. In multivariate analysis, symptomatic mitochondrial toxicity was significantly associated with didanosine-containing antiretroviral regimens (odds ratio 46; 95% CI, 7.4 to infinity; P < 0.001), but not with stavudine or with nucleoside reverse transcriptase inhibitor regimens not containing didanosine. The incidence of symptomatic mitochondrial toxicity was 200.2 per 1000 patient-years in patients receiving didanosine. Demographic characteristics were not associated with symptomatic mitochondrial toxicity. Conclusions:Coadministration of ribavirin with didanosine should be avoided. If unavoidable, patients should be monitored closely for mitochondrial toxicity. Didanosine should be suspended if clinical signs or symptoms of mitochondrial toxicity occur.

Hepatic steatosis in HIV-HCV coinfected patients: analysis of risk factors.

Objective:To evaluate the prevalence and severity of steatosis and possible interactions between steatosis, host factors, viral factors, and treatment for HIV infection in HIV–hepatitis C virus (HCV) coinfected patients. Methods:Steatosis was assessed among 395 HIV–HCV coinfected patients who were enrolled in the ANRS trial HC02 Ribavic and for whom histological data were available. Steatosis was graded as follows: 0 (none); 1 (< 30% hepatocytes containing fat); 2 (30–70%); 3 (> 70%). Results:Steatosis was present in 241 patients (61%), of whom 149 (38%) had grade 1, 64 (16%) grade 2 and 28 (7%) grade 3. In multivariate analysis, the following five independent risk factors were associated with steatosis: HCV genotype 3 [odds ratio (OR), 3.02; 95% confidence interval (CI), 1.91–4.79; P < 0.0001], the mean METAVIR fibrosis score (OR, 1.43; 95% CI, 1.11–1.84; P = 0.0053), the body mass index (BMI; OR, 1.13; 95% CI, 1.05–1.21; P = 0.0013), HCV viral load (OR. 1.65; 95% CI, 1.22–2.23; P = 0.0012) and ferritin (OR, 1.13; 95% CI, 1.06–1.21; P < 0.0003). As HCV genotype 3 was a risk factor for steatosis, further exploratory analyses were stratified according to the HCV genotype (1 and 3). Factors independently associated with steatosis were BMI and HCV viral load in patients with HCV genotype 3 infection and the mean METAVIR fibrosis score, the BMI and ferritin in patients with HCV genotype 1 infection. Conclusion:Steatosis is particularly frequent in HIV–HCV coinfected patients, who appear to have the same risk factors for steatosis as HCV monoinfected patients. None of the characteristics of HIV infection, including antiretroviral therapy, was independently associated with steatosis.

Ninety-Six—Week Efficacy of Combination Therapy with Lamivudine and Tenofovir in Patients Coinfected with HIV-1 and Wild-Type Hepatitis B Virus

We describe 6 patients who were coinfected with human immunodeficiency virus (HIV) type 1 and wild-type hepatitis B virus (HBV), in whom complete and sustained antiviral activity against wild-type HBV strains was attained during 96 weeks of combination therapy with lamivudine and tenofovir. The use of combination therapy with lamivudine and tenofovir for the treatment of HBV infection is very promising in the treatment of HIV/HBV coinfection.

Progression of Fibrosis in HIV and Hepatitis C Virus-Coinfected Patients Treated with Interferon plus Ribavirin-Based Therapy: Analysis of Risk Factors

BACKGROUND We determined the prevalence and determinants of worsening fibrosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were receiving anti-HCV therapy. METHODS Among 383 HIV-HCV-coinfected patients who received at least 1 dose of anti-HCV treatment (weekly subcutaneous injections of 1.5 mug/kg pegylated interferon-alpha-2b plus daily ribavirin or thrice-weekly subcutaneous injections of 3 MU of interferon-alpha-2b plus daily ribavirin for 48 weeks), paired pretreatment and posttreatment liver biopsy specimens were available and interpretable for 198 cases. Hepatic necroinflammation and fibrosis were graded with Ishaks classification. Histological worsening of fibrosis was defined as a score increase of > or =2 points in patients with fibrosis stage of <4 and as a score increase of 1 point in patients with stage-5 fibrosis. RESULTS The mean interval +/- standard deviation between the 2 biopsies was 109 +/- 34 weeks. Fibrosis worsened in 34 patients (17.1%). In univariate analysis, ongoing antiretroviral therapy, failure to achieve a sustained viral response, nucleoside reverse-transcriptase inhibitor therapy, didanosine therapy, and stavudine therapy were significantly associated with worsening of fibrosis. Didanosine (odds ratio, 3.34; 95% confidence interval, 1.39-7.96; P = .007) and failure to have a sustained viral response (odds ratio, 9.05; 95% confidence interval, 2.06-39.66; P = .003) remained significantly associated with worsening of fibrosis. CONCLUSION The mitochondrial toxicity of antiretrovirals, such as didanosine, seems to play a major role in worsening of fibrosis during HCV therapy. Therefore, anti-HCV therapy should ideally be administered before antiretroviral treatment initiation. If anti-HCV and anti-HIV treatments have to be administered concomitantly, then nucleoside reverse-transcriptase inhibitors with the lowest mitochondrial toxicity should be preferred.

Spontaneous Hepatic Decompensation in Patients Coinfected with HIV and Hepatitis C Virus during Interferon-Ribavirin Combination Treatment

Spontaneous hepatic decompensation was observed in 7 of 383 patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were receiving treatment with interferon and ribavirin. Multivariate analysis identified the following risk factors: didanosine use (odds ratio [OR], 8.8; 95% confidence interval [CI], 1.2-102.3; P < .02), cirrhosis, (OR, 8.8; 95% CI, 1.2-104.2; P<.02), and elevated total bilirubin level (OR, 7.9; 95% CI, 1.08-93.3; P<.03). Didanosine should thus not be given to patients with cirrhosis, particularly when treatments for HCV and HIV infections have to be administered concomitantly.

Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients

Summary.  The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV‐coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV‐coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non‐nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1–3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1–3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2–3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0–2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0–1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV‐coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.

All-oral Direct-acting Antiviral Regimens in HIV/Hepatitis C Virus–coinfected Patients With Cirrhosis Are Efficient and Safe: Real-life Results From the Prospective ANRS CO13–HEPAVIH Cohort

BACKGROUND Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce. METHODS Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome. RESULTS We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA <50 copies/mL; 99% on antiretrovirals; median CD4 count: 489 cells/µL; HCV treatment naive 29%; HCV genotype 1/2/3/4: 58%/4%/17%/21%. Sofosbuvir (SOF) + daclatasvir ± ribavirin (RBV) was used in 123 patients, SOF + RBV in 30, SOF + simeprevir in 11, and SOF + ledipasvir in 23. An SVR12 was reported in 93.1% of the patients (95% confidence interval, 88.5%-96.3%). In adjusted analyses, no difference was found between 12 or 24 weeks of treatment, in patients receiving RBV or not, and in treatment-naive vs experienced patients. Premature stop of DAA was reported for 8 patients. One patient died during treatment (unknown cause), and 12 other patients developed liver-related events. CONCLUSIONS In this prospective real-life cohort, all-oral DAA regimens were well tolerated and associated with a high virologic efficacy in cirrhotic HIV/HCV-coinfected patients. This should not alleviate the surveillance for liver-related events in these patients.

Antiretroviral therapy and sustained virological response to HCV therapy are associated with slower liver fibrosis progression in HIV-HCV-coinfected patients: study from the ANRS CO 13 HEPAVIH cohort.

BACKGROUND The aim of this study was to describe changes in repeated liver stiffness (LS) measurements and to assess the determinants of increase in LS in HIV-HCV-coinfected patients. METHODS HIV-HCV-coinfected adults enrolled in the ANRS CO 13 HEPAVIH cohort, for whom two results of LS, evaluated over ≥24 months, were available. Patients with unreliable LS results were not included. LS was measured at baseline and every year thereafter. Determinants of LS increase were assessed using linear (primary outcome: last LS minus first LS value) and logistic (secondary outcome: ≥30% increase in the initial LS value) regression analyses. RESULTS A total of 313 patients (mean age 45 years, 67.4% male) were included. Overall, 93.9% were receiving antiretroviral treatment (ART). The mean baseline CD4(+) T-cell count was 471 cells/mm(3) and 72.2% of patients had undetectable plasma HIV RNA. The mean interval between the first and last LS measurements was 33.5 months. No significant difference was found between baseline and follow-up mean LS values (P=0.39). However, a decrease of ≥30% in LS was observed in 48 (15.3%) patients and an increase of ≥30% in 64 (20.5%) patients. In multivariate linear and logistic analyses, excessive alcohol intake (β coefficient 6.8; P=0.0006) and high HCV viral load (OR 1.7, 95% CI 1.1, 2.5; P=0.01) were independently associated with an increase in LS, whereas time on ART>114.5 months (OR 0.5, 95% CI 0.3, 0.9; P=0.03) and achievement of sustained virological response (OR 0.1, 95% CI 0.01, 0.9; P=0.04) were independently associated with no increase in LS. CONCLUSIONS Our findings show that long-term ART and achieving sustained virological response in HIV-HCV-coinfected patients are both significantly associated with lack of increase in LS over a 33-month period.

Risk factors for anaemia in human immunodeficiency virus/hepatitis C virus-coinfected patients treated with interferon plus ribavirin

Summary.  The most frequent and the most troublesome adverse effect of interferon plus ribavirin‐based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)‐coinfected patients receiving anti‐HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48‐week trial comparing peginterferon (peg‐IFN) alpha 2b plus ribavirin with interferon alpha‐2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty‐one (15.9%) of the 383 patients who received at least one dose of anti‐HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64–6.54, P = 0.0008) and peg‐IFN (OR, 2.35; 95% CI, 1.16–4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26–0.49, P < 0.0001) and in patients receiving protease inhibitor‐based antiretroviral therapy (OR, 0.51 95% CI, 0.30–0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti‐HCV therapy.

Bartonella henselae Infection Mimicking a Splenic Lymphoma

We report a Bartonella henselae infection in a 40-y-old patient who presented with fever, weight loss, night sweats, elevated lactate dehydrogenase and multinodular splenomegaly with multiple abdominal lymphadenopathies. Splenic cat-scratch disease is an exceptional diagnosis in adults and can easily be mistaken for a splenic lymphoma, thereby leading to an unnecessary splenectomy.We report a Bartonella henselae infection in a 40-y-old patient who presented with fever, weight loss, night sweats, elevated lactate dehydrogenase and multinodular splenomegaly with multiple abdominal lymphadenopathies. Splenic cat-scratch disease is an exceptional diagnosis in adults and can easily be mistaken for a splenic lymphoma, thereby leading to an unnecessary splenectomy.