Prolonged antiretroviral therapy is associated with fewer anal high-grade squamous intraepithelial lesions in HIV-positive MSM in a cross-sectional study.

OBJECTIVE: HIV-positive men who have sex with men (MSM) are at increased risk of anal cancer. We evaluate the risk factors for anal high-grade squamous intraepithelial lesion (HSIL) (the precursor of anal cancer) in HIV-positive MSM. METHODS: In this cross-sectional study within a cohort, 320 HIV-positive MSM were screened by anal cytology followed by high-resolution anoscopy (HRA) in case of abnormal cytology. Risk factors for anal HSIL were analysed. RESULTS: Men were mostly middle-aged Caucasians with median CD4+ T lymphocytes of 638 cells/µL, 87% on combined antiretroviral therapy (cART) for a median of 5 years. 198 anal cytology samples were normal. In the 122 patients with abnormal cytology, HRA with biopsies were performed: 12% (n=15) normal, 36% (n=44) anal low-grade squamous intraepithelial lesion (LSIL) and 51% (n=63) anal HSIL. Comparing patients with or without anal HSIL (normal cytology or normal biopsy or LSIL), we found in multivariate analysis significantly fewer anal HSIL in patients with cART ≥24 months (OR 0.32 CI 95% 0.162 to 0.631, p=0.001). CONCLUSIONS: Prolonged cART (≥24 months) is associated with fewer anal HSIL.

A regular screening for hepatitis delta virus among chronic hepatitis B carriers improves the diagnostic of this infection and of subsequent cirrhosis development.

BACKGROUND AND OBJECTIVE: The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients. METHODS: Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2). RESULTS: We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7 years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p = 0.026). CONCLUSION: A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA.

Helicobacter pylori and Human Immunodeficiency Virus Co-Infection: Potential Implications for Future Gastric Cancer Risk.

OBJECTIVE: Helicobacter pylori and human immunodeficiency virus (HIV) are both pandemic infections with variable geographic prevalence rates. H. pylori-HIV co-infection at the regional and sub-regional levels with a perspective on gastric cancer incidence is discussed. DESIGN: Based on PRISMA guidelines, national data for H. pylori, HIV, and H. pylori-HIV co-infection were collected for the general population through December 2019. Joint temporal and geographical data for H. pylori and HIV infections in 48 countries were available and used to generate H. pylori-HIV co-infection estimates by cross-sectional analysis. These data were compared with gastric carcinoma statistics for the same countries. RESULTS: The estimated global prevalence rate of H. pylori-HIV co-infection was 1.7 per 1000 people, representing 12.6 million people. Prevalence according to region was, in decreasing order, sub-Saharan Africa 21.9‱, Eastern Europe/Central Asia 4.3‱, Latin America/Caribbean 2.0 ‱, North America/Western/Southern/Northern Europe 1.1‱, Asia/Pacific 0.8‱, and North Africa/Middle East 0.1 ‱. The incidence and mortality rates for gastric carcinoma were higher in East/Pacific Asia, Southern/Andean Latin America, and Eastern Europe regions, and the incidence appeared to be 1.8-fold greater in H. pylori-HIV-infected people in East Asia. CONCLUSIONS: The population at risk of H. pylori-HIV co-infection is estimated to be 12.6 million people (2015 reference year). The heterogeneity of H. pylori-HIV co-infection across regions and sub-regions does not show a clear association with gastric carcinoma. Other methodological approaches with analytical studies (cohort, case-control) are required to measure the potential effect of H. pylori infection and its treatment on the incidence of gastric carcinoma in the large HIV-H. pylori-positive cohort.

Primary Helicobacter pylori resistance to antimicrobials in the Brussels area in 2021.

This manuscript summarizes current primary resistance of Helicobacter pylori to antibiotics in Brussels in 2021. Resistance rates were estimated at 18% for clarithromycin, 24% for levofloxacin, 52% for metronidazole, and 0% for amoxicillin and tetracycline. When compared to 2016, resistance rates remain stable, except an increase of 30% for metronidazole.

Comparison of demographic characteristics and upper gastrointestinal endoscopy findings in HIV-positive, antiretroviral-treated patients with and without Helicobacter pylori coinfection.

OBJECTIVES: We evaluated demographic characteristics in HIV-positive patients receiving highly active antiretroviral therapy (HAART) who had upper gastrointestinal (UGI) symptoms requiring UGI endoscopy and compared the findings in patients with and without H. Pylori coinfection. METHODS: We prospectively observed all HIV-infected patients treated with antiretroviral therapy who underwent UGI endoscopy for the first time and were tested for H. pylori from January 2004 to December 2008. Data collected included the following: demographics (age, gender, ethnicity, body mass index [BMI], tobacco use, alcohol intake, and HIV risk behavior); comorbidity (viral hepatitis B or C, any organ dysfunction, or opportunistic disease); medication, including antibiotics, H2 blockers, proton pump inhibitors, and NSAIDs; CD4 cell counts, viral load; symptoms; and endoscopic and histologic diagnoses (H. pylori determined by Giemsa staining). Patients were compared according to H. pylori status (presence vs absence). RESULTS: One hundred and forty-five patients were evaluated. Compared to patients without H. pylori infection (n = 97), those with H. pylori infection (n = 48) had a significantly higher CD4 cell count (p = .008), were more likely to be heterosexual (p = .047), had a higher BMI (p = .027), had a greater incidence of duodenal ulcers (p = .005), had lower viral loads (p < .01), were less likely to have received macrolide antibiotics in the last 3 months (p = .00), and had less comorbidity (p = .03). They were also more frequently of Black African than Caucasians. In multivariate analysis, being heterosexual and having a low viral load were independently associated with an increased risk of having H. Pylori coinfection. CONCLUSION: In the antiretroviral therapy era, HIV-H. pylori coinfection is associated with a greater incidence of duodenal ulcers and higher CD4 counts, higher BMI, less comorbidity, and less frequent use of macrolides.

Issues Related to the Treatment of H. pylori Infection in People Living with HIV and Receiving Antiretrovirals.

Treatment of Helicobacter pylori infection in people living with HIV is associated with several challenges, including those related to drug metabolism which plays a major role in treatment efficacy. In this review, we will discuss the enzymes involved in the metabolism of anti-Helicobacter pylori and anti-HIV drugs to provide a basis for understanding the potential for interactions between these drug classes. We will also provide a clinical perspective on other issues related to the treatment of Helicobacter pylori and HIV infections such as comorbidities, adherence, and peer communication. Finally, based on our understanding of the interplay between the above issues, we propose a new concept "Antimicrobial susceptibility testing-drug interaction-supports-referent physician" (AISR), to provide a framework for improving rates of H. pylori eradication in people living with HIV.

Primary antibiotic resistance of Helicobacter pylori isolates is twofold more frequent in HIV-positive than HIV-negative individuals: A descriptive observational study.

The antimicrobial susceptibility of Helicobacter pylori strains isolated from HIV-positive individuals is not well characterized. This study aimed to measure the prevalence and long-term trends associated with primary H. pylori antibiotic resistance, evaluate correlations with antibiotic consumption, and compare predictors for H. pylori antibiotic resistance between HIV-positive and HIV-negative individuals. In this longitudinal registry study, we evaluated consecutive adults with and without HIV infection, naïve to H. pylori treatment, who underwent upper gastrointestinal endoscopy and had a positive H. pylori culture, with susceptibility testing available, between 2004 and 2015. Outpatient antibiotic consumption data were based on nationwide aggregated numbers. H. pylori was isolated from gastric biopsies of 3008/8321 patients, 181/477 (37.9%) were HIV-positive and 2827/7844 (36.0%) HIV-negative. Overall cohort mean prevalence of H. pylori primary antibiotic resistance was 11.1% for clarithromycin, 17.8% levofloxacin, and 39.4% metronidazole. The prevalence of H. pylori primary resistance was significantly higher for these three drugs in HIV-positive individuals across the study period. Linear regression showed that the prevalence of clarithromycin and levofloxacin resistance correlated with the country aggregate daily dose consumption of macrolides and quinolones, respectively. Multivariable regression analysis showed that HIV infection is a strong independent risk factor for multiple H. pylori antibiotic resistance. In summary, HIV infection is a risk factor for carrying multi-resistant H. pylori strains and this is correlated with antibiotic consumption. Empirical therapies should be avoided in HIV-positive individuals. These data highlight the need to implement ongoing monitoring of H. pylori antimicrobial susceptibility among HIV-positive individuals. The study is registered at ISRCTN registry, number 13466428: https://www.isrctn.com/ISRCTN13466428.

Metabolic disorders associated with chronic hepatitis C: impact of genotype and ethnicity.

BACKGROUND & AIM: Patients with hepatitis C virus (HCV) infection, especially those with genotypes 1 and 4, have an increased risk of developing metabolic disorders. The aim of this study was to evaluate the associations among metabolic disorders, ethnicity and genotype in a large cohort of patients with chronic hepatitis C (CHC). PATIENTS AND METHODS: All consecutive patients with CHC who were seen in our hepato-gastroenterology unit between January 2002 and September 2008 were included. Demographical data and variables related to the metabolic syndrome were collected. Insulin resistance was assessed using the homeostasis model for the assessment of insulin resistance test (HOMA-IR) test. RESULTS: Among the 454 CHC patients, the prevalence of the metabolic syndrome was 12.4%. The HOMA-IR test was performed in 140 patients, and 35.0% had insulin resistance. There were more Black Africans among the patients with genotypes 1/4 than among those with genotypes 2/3 (32.0 vs 1.2%, P<0.0001). Insulin resistance was more common in patients with genotypes 1/4 than in those with genotypes 2/3 (17 vs 1.7%, P=0.0001 and 43.3 vs 16.3%, P=0.001, respectively). Genotypes 1/4 were more frequently present in patients with insulin resistance than in those without insulin resistance (85.7 vs 60.5%, P=0.001). By logistic regression, genotypes 1/4 [odds ratio (OR)=2.79; 95% confidence interval (CI): 1.09-7.12, P=0.032] and older age (OR=1.03; 95% CI: 1.004-1.06, P=0.024) were independently associated with the presence of insulin resistance. CONCLUSIONS: In CHC, insulin resistance is independently associated with the presence of genotypes 1/4. Ethnicity is not independently associated with metabolic disorders in patients with CHC.

Treatment of anal dysplasia in HIV-positive men who have sex with men in a large AIDS reference centre.

OBJECTIVES: Over the last few decades, incidence of anal cancer among HIV-positive men has been on the rise. In this context, programmes of screening and treatment of anal dysplasia which is a precursor of anal cancer have been developed. The aim of our study was to describe the efficiency, side effects and outcome of anal dysplasia treatment in a population of HIV-positive men who have sex with men (MSM). METHODS: We performed a retrospective study of HIV-positive MSM who received treatment for anal dysplasia between May 2010 and February 2014 in the Saint-Pierre University Hospital, Brussels. The different treatments used were electrocautery (ECA), infrared coagulation (IRC), surgical treatment and imiquimod. RESULTS: Seventy-three HIV-infected MSM were included in the study, counting 62% of HGAIN. Median age was 41 years. Eighty-one per cent were on HAART. Median CD4 cell count was 525 cell/mm³, and 65% had undetectable viral loads. A total of 139 therapeutic interventions were recorded during the study period, and two-thirds of the enrolled patients received more than one treatment. At 540 days of follow-up, the rate of treatment response was 62%. Fifty per cent of the persistent HGAIN were metachronous lesions. No severe adverse events were recorded but frequent treatment-associated discomfort was reported, such as pain, self-limited bleeding, infection and anal irritation. CONCLUSION: Treatment of anal dysplasia appears to be safe and to offer short-term efficiency. However, its long-term efficiency remains unknown, especially in the HIV-positive population in which spontaneous clearance is lower and rate of recurrence higher.

Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective.

Chronic hepatitis C treatment has continued to evolve, and interferon-free, oral treatment with direct-acting antiviral agents is the current standard of care. Recently, a new treatment, which is a combination of two direct-acting antiviral agents, ledipasvir 90 mg (anti-NS5A) and sofosbuvir 400 mg (anti-NS5B), has been approved in the US and the European Union for the treatment of chronic hepatitis C viral infection. In Phase III trials among chronic hepatitis C virus genotype 1 monoinfected (treatment-naïve, treatment-experienced, and with advanced liver disease or posttransplant) patients and HIV-hepatitis C virus coinfected patients, the ledipasvir-sofosbuvir fixed-dose combination is associated with a higher rate of sustained virologic response at 12 weeks after therapy has ceased. According to preliminary data, the ledipasvir-sofosbuvir combination also may be effective against hepatitis C genotype 4 virus infection. The ledipasvir-sofosbuvir combination taken orally is generally well-tolerated. Moreover, the combination treatment may suppress the effect of predictive factors of chronic hepatitis C that have historically been known to be associated with treatment failure. Thus, the fixed-dose single-tablet combination of ledipasvir-sofosbuvir offers a new era for the effective treatment of a variety of patients suffering from chronic hepatitis C virus infection.

The role of upper gastrointestinal endoscopy in the era of modern antiretroviral therapy.

OBJECTIVE: Gastrointestinal disorders are common in HIV-positive patients and, in some cases, may be related to antiretroviral therapy (ART), making it difficult to determine the need for upper gastrointestinal (UGI) endoscopy. The primary aim of this study was to determine whether lymphocyte T CD4 cell counts were correlated with indications for endoscopy in these patients and with endoscopic diagnosis. PATIENTS AND METHODS: We prospectively collected data from consecutive HIV-positive patients undergoing UGI endoscopy between 2007 and 2013, and included 265 patients who had been receiving ART for at least 6 months. Parameters studied were demographics, immune parameters, comorbidities, comedications, indications for endoscopy, and endoscopic, pathologic, and microbiologic findings. RESULTS: The most frequent indications for UGI endoscopy were gastroesophageal reflux, epigastric pain, and other. Peptic esophagitis, esophageal candidiasis, and normal endoscopy were the most common diagnoses. The prevalence rates of Helicobacter pylori infection and neoplasia were 26.4 and 1.8%, respectively. Patients with CD4+ counts 200 cells/µl or more had significantly lower rates of macrolide and nonmacrolide use, fewer comorbidities, and were less likely to have AIDS than patients with lower counts. They were also more likely to have normal UGI endoscopy and had a higher frequency of H. pylori infection. AIDS status and the presence of comorbidities were independent predictors of endoscopic abnormalities. CONCLUSION: UGI endoscopy remains a key diagnostic procedure for HIV-positive patients with UGI symptoms. AIDS and comorbidities are risk factors for the presence of mucosal lesions among HIV-positive patients on ART.

HIV-Helicobacter pylori Co-Infection: Antibiotic Resistance, Prevalence, and Risk Factors.

BACKGROUND: Patients infected with human immunodeficiency virus (HIV) are living longer due to the availability of more potent treatments. However, prescription of antibiotics to treat or prevent infections in these patients may increase the likelihood of co-infection with antibiotic-resistant species. AIM: To compare antimicrobial susceptibility of Helicobacter pylori (H. pylori) in HIV-positive and HIV-negative patients and assess risk-factors for resistance. METHODS: We prospectively collected data from consecutive HIV-positive and HIV-negative patients undergoing upper gastrointestinal endoscopy. Patients with H. pylori-positive gastric biopsies who had never received H. pylori treatment were included. RESULTS: Of the 353 patients included, 93 were HIV-positive and 260 HIV-negative. Among the HIV-positive patients, 56 (60%) had been infected for <10 years, the median CD4+ count was 493 cells/µl and median viral load was 61 copies/mL; 66 (71%) were receiving antiretroviral therapy. HIV-positive patients were more often male (p = 0.009), had a lower body mass index (p<0.0001), and had less frequently received antibiotics during the 12-months prior to the endoscopy (p<0.0001) than HIV-negative patients. HIV-positive patients were more likely to have H. pylori resistant to levofloxacin (p = 0.0004), metronidazole (p = 0.01), or multiple antibiotics (p = 0.006). HIV-positive Black Africans were more likely to have resistant strains than were HIV-negative Black Africans (p = 0.04). Ethnicity and HIV status were independent risk factors for H. pylori resistance in all patients and acquired immune deficiency syndrome (AIDS) and sex were risk factors in HIV-positive patients. CONCLUSIONS: There was a higher prevalence of primary H. pylori-resistant strains in HIV-positive than in HIV-negative patients. AIDS and sex were predictors of H. pylori resistance in HIV-positive patients.

Ethnic epidemiological profiles and antiviral therapy among patients infected with hepatitis C virus genotype 4: a multicenter study from Belgium.

BACKGROUND: Hepatitis C virus genotype 4 (HCV-4) is the most prevalent genotype in Central Africa. AIM: To compare epidemiology, clinical characteristics and any differences in access to HCV therapy in two populations of HCV-4 patients residing in Belgium. METHODS: This multicenter study selected 473 HCV-4 patients from seven hospital databases and compared them according to ethnic origin, i.e., Black African (n=331) or not (n=142), for epidemiological, clinical, biological and histological characteristics. Interleukin 28B polymorphism (CC-genotype) was evaluated in a second cohort of 69 Black African and 30 non-Black African patients. RESULTS: Compared to other patients, the Black African patients were more likely to be female and were older, commonly overweight, frequently had abnormal glucose metabolism and arterial hypertension ; they were less likely to have dyslipidemia, a history of alcohol consumption or ALT elevation. The route of infection was more frequently unknown in Black African than in other patients. Black African patients had more HCV-4 subtypes, were less frequently of IL28B CC-genotype and had less severe liver fibrosis. The proportion of patients who received antiviral treatment was similar in the two groups. CONCLUSION: In this Belgian cohort, patients with HCV-4 infection were more frequently of Black African origin than of other origin. Infected Black African patients were more commonly -female, older at diagnosis, and had more co-morbidities than other patients; they also had less advanced liver fibrosis than infected non-Black African patients and fewer had a CC genotype.