Changes in body mass index and clinical outcomes after initiation of contemporary antiretroviral regimens.

BACKGROUND: Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective observational study. METHODS: PWH aged ≥18 years were included who started a new antiretroviral (baseline) during 2010-2019 with baseline and ≥1 follow-up BMI assessment available. Rates of clinical outcomes (cardiovascular disease [CVD], malignancies, diabetes mellitus [DM] and all-cause mortality) were analysed using Poisson regression to assess effect of time-updated BMI changes (>1 kg/m 2 decrease, ±1 kg/m 2 stable, >1 kg/m 2 increase), lagged by 1-year to reduce reverse causality. Analyses were adjusted for baseline BMI plus key confounders including antiretroviral exposure. RESULTS: 6721 PWH were included; 72.3% were male, median age 48 years (interquartile range [IQR] 40-55). At baseline, 8.4% were antiretroviral-naive, and 5.0% were underweight, 59.7% healthy weight, 27.5% overweight, and 7.8% were living with obesity. There was an 8.2% increase in proportion of overweight and 4.8% in obesity over the study period (median follow-up 4.4 years [IQR 2.6-6.7]).100 CVDs, 149 malignancies, 144 DMs, and 257 deaths were observed with incidence rates 4.4, 6.8, 6.6, 10.6 per 1000 person-years of follow-up, respectively. Compared to stable BMI, >1 kg/m 2 increase was associated with increased risk of DM (adjusted incidence rate ratio [IRR]: 1.96, 95% confidence interval [CI]: 1.36-2.80) and >1 kg/m 2 decrease with increased risk of death (adjusted IRR: 2.33, 95% CI: 1.73-3.13). No significant associations were observed between BMI changes and CVD or malignancies. CONCLUSIONS: A BMI increase was associated with DM and a decrease associated with death.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Low performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Hepatocellular carcinoma after sustained virological response with interferon-free regimens in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

A case-control study of non-AIDS-defining cancers in a prospective cohort of HIV-infected patients. / Estudio caso-control de tumores no definitorios de sida en una cohorte prospectiva de pacientes infectados por el VIH.

INTRODUCTION: We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. METHODS: All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. RESULTS: Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality. CONCLUSIONS: Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

Comparison of high ribavirin induction versus standard ribavirin dosing, plus peginterferon-α for the treatment of chronic hepatitis C in HIV-infected patients: the PERICO trial.

BACKGROUND: Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 µg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin ß (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. RESULTS: A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 µg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. CONCLUSIONS: A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.

Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain.

BACKGROUND: Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion. METHODS: Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI). RESULTS: A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9). CONCLUSIONS: A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.

Preemptive erythropoietin plus high ribavirin doses to increase rapid virological responses in HIV patients treated for chronic hepatitis C.

Chronic hepatitis C affects one-third of HIV(+) patients worldwide. High ribavirin (RBV) exposure is crucial to maximize the response to hepatitis C therapy in this population, although it may increase the risk for hemolytic anemia. PERICO is a prospective multicenter trial in which HIV/HCV-coinfected patients are randomized to receive peginterferon (pegIFN) alfa-2a 180 microg/week plus either weight-based RBV (1000-1200 mg/day) or RBV 2000 mg/day, the latest along with erythropoietin alfa (EPO) 30,000 IU/week from the first day until week 4. A total of 149 patients were assessed in a planned interim analysis at week 4. In both arms, 22% of patients achieved negative HCV-RNA (rapid virological response, RVR). Multivariate analysis [OR (IC 95%), p] showed that factors associated with RVR were HCV genotypes 2/3 vs. 1/4 [20 (5-100), <0.01] and baseline HCV-RNA [0.16 (0.07-0.37) per log IU/ml, <0.01]. The occurrence of severe anemia (hemoglobin <10 g/dl) did not differ when comparing RBV vs. high RBV + EPO (7% vs. 3%; p = 0.4). Moreover, RBV plasma trough levels were comparable at week 4 (1.9 vs. 2.4 microg/ml; p = 0.2). Use of high RBV doses with preemptive EPO during the first 4 weeks of hepatitis C therapy is safe, but fails to enhance significantly RBV plasma exposure and RVR rates. Extensive intraerythrocyte accumulation of RBV following boosted production of red blood cells by EPO could explain these findings.

[Factors related to non-prescription of tuberculin skin testing in a cohort of HIV-infected people]. / Factores asociados con la no realización de la prueba de la tuberculina en una cohorte de pacientes VIH positivos.

INTRODUCTION: Tuberculin skin testing (TST) for tuberculosis (TB) is recommended for all patients with HIV infection because of the known relationship between these two conditions. In this report we analyze the incidence and variables associated with non-prescription of TST in a cohort of HIV-infected people. PATIENTS AND METHODS: Longitudinal study conducted between 2000 and 2002 at 10 HIV hospital-based clinics. All HIV-infected patients who had not been regularly followed-up previously in dedicated clinics were identified. Data about TST and other variables related to TB were obtained from the clinical records. We calculated the percentage of patients who did not undergo TST and the associated factors, using odds ratios (ORs) and the 95% CI to investigate associations. A multivariate logistic regression analysis was performed. RESULTS: A total of 1242 patients met the inclusion criteria. TST was not performed in 185 patients (17.6% of those eligible). The fact of being an intravenous drug abuser was associated with a higher probability of TST non-prescription (OR: 2.6, 95% CI 1.1-6.5), whereas being unemployed (OR: 0.6, 95% CI 0.3-1.0), having a CD4 cell count >200 (CD4 200-499: OR 0.5, 95% CI 0.3-0.9. CD4> or =500: OR 0.3, 95% CI 0.2-0.6), and contact with persons with TB (OR 0.2, 95% CI 0.1-0.5) were associated with a lower probability. CONCLUSIONS: In this study, the percentage of TST non-prescription was quite high. The results suggest that TST non-prescription in this population is related to the clinicians' expectations regarding the results of the test and the patients' adherence to treatment for latent TB infection.

Long-term effectiveness and safety outcomes in HIV-1-infected patients after a median time of 6 years on nevirapine.

To report long-term data on safety and effectiveness of antiretroviral regimens, including nevirapine. HIV-1-infected patients who received nevirapine-based approaches for at least 4 years were identified in the databases of five centers and included in a retrospective cohort study. Data collected included plasma HIV-RNA (viral load) and CD4+ T-cell counts, lipid and liver function tests, at baseline, 2-year and > 4-year time points. Hepatitis C virus (HCV) coinfection, adverse events, and reasons for using nevirapine were also recorded. Two hundred and twenty-nine patients (139 males/90 females) were included. The mean age was 37 years (range 20-59). Most patients (n = 124; 54%) were former intravenous drug users. One hundred and thirty-five of the patients (59%) were coinfected with HCV. Median time on nevirapine was 72.6 months. The main reasons for nevirapine use included: second- or third-line therapy (39%), simplification of therapy (29%), first-line therapy (18%) and efavirenz intolerance (9%). LDL cholesterol and triglycerides decreased during the >4-year follow-up (135 mg/dl to 109 mg/dl, p = 0.04; and 216 mg/dl to 153 mg/dl, p<0.01, respectively), and HDL cholesterol increased from 48 mg/dl at baseline to 62 mg/dl (p<0.01). Liver enzymes remained without significant changes during follow-up. The reported follow-up pattern of laboratory tests was also found in the subset of HCV-coinfected patients, where men and women were compared and patients with a CD4+ cell count cut-off value of 250/mm(3) were stratified. Mean CD4+ T-cell counts increased from 439/mm(3) at baseline to 628/mm(3) at the last available visit (p<0.001). Ninety-four per cent (172 out of 184) of patients who remained on nevirapine-based therapy at last visit maintained viral load values below the limit of detection (<50 copies/ml). Throughout the follow-up nevirapine was stopped or withdrawn in 43 patients due to virological failure (n = 17), toxicity (n = 5), therapy interruption (n = 3), death (n = 2), dyslipidemia (n = 1), simplification (n = 1) or unknown reasons (n = 14). Adverse events were reported in 40 patients but none was directly attributed to nevirapine. Nevirapine-based antiretroviral therapy provides sustained immunological and virological effectiveness over a more than 4-year treatment period as well as a beneficial lipid metabolic profile and a favorable safety profile, even in HCV-coinfected patients and women with CD4+ cell counts above 250/mm(3). The study data support a nevirapine-based approach as a suitable long-term strategy in the HIV-1-infected population.

Nephrogenic systemic fibrosis in a patient with a p-ANCA systemic vasculitis.

Nephrogenic systemic fibrosis (NSF) is a fibrosing skin condition of unknown origin. Most cases have been described in patients with acute or chronic renal failure. The cutaneous changes include firm and thickened, indurate skin plaques and papules on the extremities and trunk. Histopathology typically shows an increase in dermal fibroblast-like cells associated with mucin deposition. Previous exposition to gadolinium-based contrast agents was closely associated with its onset. We described a patient with the clinical and pathologic picture of NSF presented after an acute renal failure in the course of a perinuclear antineutrophil cytoplasmic antibodies associated systemic vasculitis.

Undetectable hepatitis C virus RNA at week 4 as predictor of sustained virological response in HIV patients with chronic hepatitis C.

BACKGROUND: Low baseline serum hepatitis C virus (HCV)-RNA and clearance of viraemia at week 4 with pegylated interferon (pegIFN) plus ribavirin therapy predict sustained virological response (SVR) and enable a shorter duration of therapy in patients with chronic hepatitis C. It is unclear whether this applies to HIV/HCV-co-infected patients. PATIENTS AND METHODS: In the Peginterferon Ribavirin ESpaña COinfection (PRESCO) trial, 389 co-infected patients received pegIFN-alpha2a 180 microg/week plus ribavirin 1000-1200 mg/day. Patients with HCV-2/3 were treated for 6 or 12 months, whereas patients with HCV-1/4 were treated for 12 or 18 months. For each genotype, baseline HCV-RNA and rapid virological response (RVR), defined as under 50 IU/ml HCV-RNA at week 4, were evaluated as predictors of SVR in an 'on-treatment' analysis. RESULTS: Overall, SVR was achieved by 193 patients (49.6%), 68/191 (35.6%) with genotype 1, 110/152 (72.4%) with genotypes 2/3 and 15/46 (32.6%) with genotype 4. RVR was the best predictor of SVR regardless of HCV genotype. Only for HCV-1 patients, baseline HCV-RNA less than 500 000 IU/ml was also associated with SVR. In HCV-3 patients RVR had a positive predictive value (PPV) for SVR of 90%, with treatment for 24 or 48 weeks. The PPV of SVR for patients with RVR was 69% for HCV-1 and 83% for HCV-4. CONCLUSION: Undetectable HCV-RNA at week 4 is the best predictor of curing chronic hepatitis C in HCV/HIV-co-infected patients. In HCV-1 patients, baseline HCV-RNA also predicts response. HIV patients with HCV-3 and RVR may permit shortening therapy duration to only 24 weeks of pegIFN plus 1000-1200 mg ribavirin.

Rickettsia monacensis and human disease, Spain.

We identified Rickettsia monacensis as a cause of acute tickborne rickettsiosis in 2 humans. Its pathogenic role was assessed by culture and detection of the organism in patients' blood samples. This finding increases the number of recognized human rickettsial pathogens and expands the known geographic distribution of Mediterranean spotted fever-like cases.

[Epidemiological characteristics of new HIV infections compared with AIDS cases. The HIV/AIDS epidemic in the Basque Country]. / Características epidemiológicas de las nuevas infecciones causadas por el VIH comparadas con los casos de sida. La epidemia de VIH/sida en el País Vasco.

OBJECTIVE: To describe the epidemiological characteristics of new cases of HIV infection diagnosed from 1997-2001 and compare them with AIDS cases (1991-2001). METHODS: Data were retrospectively collected on new cases of HIV infection detected in the Basque Country (1997-2001) and were compared with AIDS cases (1991-2001). RESULTS: A total of 912 new cases of HIV infection were diagnosed. In 299 of the new cases (32.8%), HIV and AIDS were diagnosed simultaneously. The most common mechanism of transmission was heterosexual transmission, followed by intravenous and homo/bisexual transmission. Significant epidemiological differences (p < 0.001) were found with regard to AIDS cases. CONCLUSIONS: Sexual transmission has replaced intravenous drug use as the most common mechanism of HIV transmission. A large percentage of patients were simultaneously diagnosed with HIV and AIDS, indicating the need for new prevention strategies.