HIV Co-infected Patients Research Articles

Clinical Correlates of Hepatitis B or Hepatitis C Coinfections in People Living with HIV/AIDS (PLHIV)

Introduction: Hepatitis B virus (HBV) coinfected HIV patients are likely to have chronic hepatitis B infection and associated severe liver disease, however effect of hepatitis B on HIV has not been proven to be off any effect. Similarly in HIV/HCV co-infection majority of the studies have shown no significant influence of hepatitis C on the course of HIV infection, although some studies have demonstrated an association between HCV infection and faster HIV disease progression.14,15 Therefore, further studies are needed to study the impact of HBV/HCV co-infection on course of HIV, specially, in India. Aims and Objectives: To study the clinical, biochemical and immunological profile of PLHIV co-infected with either hepatitis B or hepatitis C virus, the severity of liver disease and hepatitis B and hepatitis C viral loads in these co-infected PLHIV and the association of WHO stage of HIV and immunosuppression with hepatitis B and hepatitis C viral loads as well as severity of liver disease. Method: It was an observational cross-sectional study, involving 30 PLHIV co-infected with either hepatitis B or C. A detailed history and physical examination was done. Complete Haemogram, Liver function tests, kidney function tests, Ultrasonography abdomen, CD4 cell counts, hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), hepatitis B Viral DNA (HBV DNA) and HCV RNA levels were done. Severity of liver disease was assessed by FIB 4 SCORE. Results: Among the 30 PLHIV subjects 30% were co-infected with HCV 70% were co-infected with HBV (HBsAg positive). All the subjects were asymptomatic for their liver disease. All the subjects were on Anti-Retroviral Therapy (ART) and 80% were in Early WHO stage (T1 and T2) and 20% were in Advanced WHO stage (T3 and T4). It was similar in both HBV and HCV co-infected group. The mean CD4 count of the subjects was 416.70±189.50 cells/mm3 with the range of 69 – 909 cells/mm3. Five subjects (16.67%) had a CD4 count 3.25). In HCV co-infected subjects 3 of 9 (33.33%) had severe liver fibrosis and only 1 of 21 (4.7%) among HBV co-infected had severe liver fibrosis.Among the 9 HCV co-infected subjects, 3 (33.33%) had undetectable HCV RNA. More number of subjects with detectable hepatitis C viral load had severe liver disease as compared to undetectable viral load.In HIV and HBV co-infected subjects the HBeAg positivity was seen in 42.86% subjects and 38.1% subjects had detectable HBV DNA load. Significant correlation was seen between HBeAg positivity and HBV DNA load. No correlation could be found between FIB 4 score and hepatitis B envelope antigen (HBeAg) positivity or HBV DNA load.No correlation between severity of liver disease (FIB 4) score and WHO staging or CD4 count could be seen. WHO staging and CD4 count also did not correlated with HCV RNA load, HBeAg positivity and HBV DNA load. Conclusions: There is no correlation of CD4 count and WHO stage with liver disease severity or hepatitis viral load in patients on HAART. In HIV and HBV co-infected patients high prevalence of HBeAg positivity is seen. Thus it becomes important to look for deranged liver enzymes and HBeAg positivity in PLHIV coinfected with hepatitis B so that ART can be initiated in these patients irrespective of CD4 count. Hepatitis C co-infected subjects are more likely to have severe liver disease inspite of good CD4 count, so specific treatment for hepatitis C virus should be considered.

Effect of high-intensity versus low-intensity praziquantel treatment on HIV disease progression in HIV and Schistosoma mansoni co-infected patients: a randomised controlled trial.

Background: It has been hypothesised that Schistosoma co-infection exacerbates HIV progression, and hence anthelminthic intervention in co-infected individuals will delay it. We evaluated effects of high-intensity versus low-intensity praziquantel treatment of schistosomiasis on HIV disease progression among co-infected patients from fishing populations around Lake Victoria, Uganda. Methods: Between August 2012 and September 2015, we conducted an open-label randomised, controlled trial. Adults, antiretroviral therapy-naïve, CD4 counts ≥350 cells/μl, HIV and S. mansoni co-infected, were randomised 1:1 to praziquantel (40mg/kg) given quarterly (starting at enrolment) or annually (starting 12 weeks after enrolment; such that low-intensity participants were still untreated when sampled at 12 weeks). A non-randomised HIV-positive S. mansoni-negative comparison group was recruited. The primary outcome was mean change in plasma viral load at 12 and 60 weeks. Results: In total 363 participants (high-intensity 113, low-intensity 113, comparison group 137) were recruited; 96 (85.0%), 97 (85.8%) and 107 (78.1%) completed 60 weeks of follow up, respectively. Adjusting for baseline age and viral load, the geometric mean ratio (aGMR [95%CI]) viral load for high-intensity vs low-intensity groups at 12 weeks was 0.90 [0.65, 1.25] p=0.55 and at 60 weeks 1.88 [0.78, 4.53] p=0.16. Results in the comparison group were similar to trial arms. High-intensity, compared to low-intensity, treatment resulted in substantially lower S. mansoni prevalence at all follow up visits (p<0.05). Conclusions: In communities with a high burden of both S. mansoni and HIV infection, high-intensity treatment of S. mansoni does not delay HIV progression despite relevant benefit for parasite clearance. Trial registration: ISRCTN15371662 (17/11/2016).

Development of colorimetric sensor array for diagnosis of tuberculosis through detection of urinary volatile organic compounds

BackgroundTop priorities for tuberculosis control and elimination include a simple, low-cost screening test using sputum and a non-sputum-based test in patients that do not produce sputum. The aim of this study was to evaluate the performance of a colorimetric sensor array (CSA) test, for analysis of volatile organic compounds in urine, in the diagnosis of pulmonary TB. Material and MethodsUrine samples were collected from individuals suspected of having pulmonary TB in Western Kenya. Reference methods included MGIT culture and/or Xpert MTB/RIF nucleic acid amplification test on sputa. Fresh urine samples were tested with the CSA, with acid and base and without an additive. The CSA were digitally imaged, and the resulting colorimetric response patterns were used for chemometric analysis. Sensitivity, specificity, and negative (NPV) and positive predictive (PPV) values were determined for HIV-positive and HIV-negative patients. ResultsIn HIV-negative patients, the highest accuracy was obtained in urine samples pre-treated with a base, yielding a sensitivity, specificity, PPV, and NPV of 78.3% (65/83), 69.2% (54/78), 73.0% (n/89) and 75.0% (n/72). The highest sensitivity of 79.5% was achieved using sensor data from all three test conditions at a specificity of 65.4%. In HIV-positive subjects, the sensor performance was substantially lower with sensitivity, specificity, PPV, and NPV ranging from 48.3% to 62.3%, 54.1% to 74.0%, 55.9% to 64.2%, and 60.6% to 64.9%, respectively. ConclusionThe CSA fingerprint of urine headspace volatiles showed moderate accuracy in diagnosing TB in HIV-negative patients, but the sensor performance dropped substantially in HIV-coinfected patients. Further development of TB-responsive CSA indicators may improve the accuracy of CSA urine assay.

The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study.

BackgroundNorth-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients.Methodology/Principal findingsWe conducted a retrospective cohort study at a Médecins Sans Frontières—supported health center in north-west Ethiopia. We included VL-HIV co-infected adults, treated for VL between January 2011 and August 2014, with AmBisome infusion (30 mg/kg total dose) and miltefosine orally for 28 days (100 mg/day). Proportions of initial treatment outcome categories were calculated. Predictors of initial parasitological failure and of death were determined using multivariable logistic regression. Of the 173 patients included, 170 (98.3%) were male and the median age was 32 years. The proportion of patients with primary VL (48.0%) and relapse VL (52.0%) were similar. The majority had advanced HIV disease (n = 111; 73.5%) and were on antiretroviral therapy prior to VL diagnosis (n = 106; 64.2%). Initial cure rate was 83.8% (95% confidence interval [CI], 77.6–88.6); death rate 12.7% (95% CI, 8.5–18.5) and parasitological failure rate 3.5% (95% CI, 1.6–7.4). Tuberculosis co-infection at VL diagnosis was predictive of parasitological failure (adjusted odds ratio (aOR), 8.14; p = 0.02). Predictors of death were age >40 years (aOR, 5.10; p = 0.009), hemoglobin ≤6.5 g/dL (aOR, 5.20; p = 0.002) and primary VL (aOR, 8.33; p = 0.001).Conclusions/SignificanceInitial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in clinical trials.

HBV and HIV viral load but not microbial translocation or immune activation are associated with liver fibrosis among patients in South Africa

BackgroundCo-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection.MethodsWe recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa. All HIV-infected patients were on antiretroviral therapy for ≥3 months. Liver stiffness measurements were assessed using the Fibroscan (Fibroscan 402, Echosens). Cell-based immunomarkers were measured by flow cytometry. Soluble serum/plasma immunomarkers were measured by Luminex technology and enzyme immunoassays. HIV (COBAS/Ampliprep TaqMan HIV-1) and HBV viral loads (in-house assay) were also performed.ResultsHBV/HIV co-infected patients showed significantly higher levels of immune activation %CD8+/HLA-DR+/CD38+ (median 30%, interquartile range: 17–53) and %CD8+/PD-1 (median 22%, interquartile range: 15–33), p ≤ 0.01 compared to all other study groups. Despite this, the HBV-mono-infected group had the highest proportion of patients with advanced liver fibrosis (≥13 kPa) as measured by Fibroscan (18%). HBV mono-infected patients showed highest expression of most cytokines including IL-17 and basic fibroblastic growth factor. There was significant positive correlation between detectable HIV and HBV viral replication and liver fibrosis but not immune activation or gut translocation.DiscussionHighly-active antiretroviral therapy, including tenofovir, is effective against both HIV and HBV. Earlier therapy in the co-infected patients may therefore have controlled viral replication leading to better fibrosis scores when compared to HBV mono-infection in this study. On-going HBV and HIV viraemia, rather than microbial translocation or immune activation, appear to be the drivers of liver fibrosis. Moderate to advanced liver fibrosis in HBV-mono-infection may well indicate poor access to screening and treatment of HBV infection.

Evolutionary dynamics of Hepatitis C virus in a chronic HIV co-infected patient and its correlation with the immune status

The HCV evolutionary dynamics play a key role in the infection onset, maintenance of chronicity, pathogenicity, and drug resistance variants fixation, and are thought to be one of the main caveats in the development of an effective vaccine. Previous studies in HCV/HIV co-infected patients suggest that a decline in the immune status is related with increases in the HCV intra-host genetic diversity. However, these findings are based on single point sequence diversity measures or coalescence analyses in several virus-host interactions. In this work, we describe the molecular evolution of HCV-E2 region in a single HIV-co-infected patient with two clearly defined immune conditions.The phylogenetic analysis of the HCV-1a sequences from the studied patient showed that he was co-infected with three different viral lineages. These lineages were not evenly detected throughout time. The sequence diversity and coalescence analyses of these lineages suggested the action of different evolutionary patterns in different immune conditions: a slow rate, drift-like process in an immunocompromised condition (low levels of CD4+ T lymphocytes); and a fast rate, variant-switch process in an immunocompetent condition (high levels of CD4+ T lymphocytes).

Mo1428 - Regression of Liver Fibrosis after SVR from Direct-Acting Antivirals (DAAS) in Hepatitis C HIV Co-Infected Patients

Mo1428 - Regression of Liver Fibrosis after SVR from Direct-Acting Antivirals (DAAS) in Hepatitis C HIV Co-Infected Patients

Prognostic score to predict mortality during TB treatment in TB/HIV co-infected patients.

BackgroundEstimating mortality risk during TB treatment in HIV co-infected patients is challenging for health professionals, especially in a low TB prevalence population, due to the lack of a standardized prognostic system. The current study aimed to develop and validate a simple mortality prognostic scoring system for TB/HIV co-infected patients.MethodsUsing data from the CDC’s Tuberculosis Genotyping Information Management System of TB patients in Texas reported from 01/2010 through 12/2016, age ≥15 years, HIV(+), and outcome being “completed” or “died”, we developed and internally validated a mortality prognostic score using multiple logistic regression. Model discrimination was determined by the area under the receiver operating characteristic (ROC) curve (AUC). The model’s good calibration was determined by a non-significant Hosmer-Lemeshow’s goodness of fit test.ResultsAmong the 450 patients included in the analysis, 57 (12.7%) died during TB treatment. The final prognostic score used six characteristics (age, residence in long-term care facility, meningeal TB, chest x-ray, culture positive, and culture not converted/unknown), which are routinely collected by TB programs. Prognostic scores were categorized into three groups that predicted mortality: low-risk (<20 points), medium-risk (20–25 points) and high-risk (>25 points). The model had good discrimination and calibration (AUC = 0.82; 0.80 in bootstrap validation), and a non-significant Hosmer-Lemeshow test p = 0.71.ConclusionOur simple validated mortality prognostic scoring system can be a practical tool for health professionals in identifying TB/HIV co-infected patients with high mortality risk.

Linking private, for-profit providers to public sector services for HIV and tuberculosis co-infected patients: A systematic review.

BackgroundTuberculosis (TB) is the leading cause of infectious disease deaths worldwide and is the leading cause of death among people with HIV. The World Health Organization (WHO) has called for collaboration between public and private healthcare providers to maximize integration of TB/HIV services and minimize costs. We systematically reviewed published models of public-private sector diagnostic and referral services for TB/HIV co-infected patients.MethodsWe searched PubMed, the Cochrane Central Register of Controlled Trials, Google Scholar, Science Direct, CINAHL and Web of Science. We included studies that discussed programs that linked private and public providers for TB/HIV concurrent diagnostic and referral services and used Review Manager (Version 5.3, 2015) for meta-analysis.ResultsWe found 1,218 unduplicated potentially relevant articles and abstracts; three met our eligibility criteria. All three described public-private TB/HIV diagnostic/referral services with varying degrees of integration. In Kenya private practitioners were able to test for both TB and HIV and offer state-subsidized TB medication, but they could not provide state-subsidized antiretroviral therapy (ART) to co-infected patients. In India private practitioners not contractually engaged with the public sector offered TB/HIV services inconsistently and on a subjective basis. Those partnered with the state, however, could test for both TB and HIV and offer state-subsidized medications. In Nigeria some private providers had access to both state-subsidized medications and diagnostic tests; others required patients to pay out-of-pocket for testing and/or treatment. In a meta-analysis of the two quantitative reports, TB patients who sought care in the public sector were almost twice as likely to have been tested for HIV than TB patients who sought care in the private sector (risk ratio [RR] 1.98, 95% confidence interval [CI] 1.88–2.08). However, HIV-infected TB patients who sought care in the public sector were marginally less likely to initiate ART than TB patients who sought care from private providers (RR 0.89, 95% CI 0.78–1.03).ConclusionThese three studies are examples of public-private TB/HIV service delivery and can potentially serve as models for integrated TB/HIV care systems. Successful public-private diagnostic and treatment services can both improve outcomes and decrease costs for patients co-infected with HIV and TB.

WAYS TO REDUCE THE IMPACT OF RISK FACTORS FOR UNFAVORABLE OUTCOMES OF TB IN HIV-INFECTED PATIENTS

To define the main risk factors of the unfavorable outcomes of tuberculosis and to propose approaches to minimizing their impact on HIV patients. Materials and methods : To define the risk factors, 710 case histories of patients with TB and HIV were examined. Approaches to minimizing the impact of the risk factors are worked out with account of international guidelines concerning TB treatment in HIV patients. Results: The risk factors of unfavorable outcomes of TB in HIV patients are social, including alcoholism and having no family (spouse), and medical, including living with HIV for three years or longer, bacterioexcretion, drug resistance of the infectious agent, and CD4 cell counts below 200. The influences of these factors are modifiable and may be minimized upon optimization of preventive interventions and reinforcement of epidemiological surveillance for co-infected HIV patients. Conclusion : Timely identification of risk factors on unfavorable outcomes of TB in HIV patients and the implementation of the proposed approaches to optimizing measures against TB will allow avoiding unfavorable outcomes of TB in HIV patients.

Hepatitis C virus cure does not impact kidney function decline in HIV co-infected patients

To examine the impact of sustained virologic response (SVR) and illicit (injection and noninjection) drug use on kidney function among hepatitis C virus (HCV) and HIV co-infected individuals. Longitudinal observational cohort study of HCV-HIV co-infected patients. Data from 1631 patients enrolled in the Canadian Co-Infection Cohort between 2003 and 2016 were analyzed. Patients who achieved SVR were matched 1 : 2 with chronically infected patients using time-dependent propensity scores. Linear regression with generalized estimating equations was used to model differences in estimated glomerular filtration rates (eGFR) between chronic HCV-infected patients and those achieving SVR. The relationship between illicit drug use and eGFR was explored in patients who achieved SVR. We identified 384 co-infected patients who achieved SVR (53% treated with interferon-free antiviral regimens) and 768 propensity-score matched patients with chronic HCV infection. Most patients were men (78%) and white (87%), with a median age of 51 years (interquartile range: 45-56). During 1767 person-years of follow-up, 4041 eGFR measurements were available for analysis. Annual rates of decline in eGFR were similar between patients with SVR [-1.32 (ml/min per 1.73 m)/year, 95% confidence interval (CI) -1.75 to -0.90] and chronic infection [-1.19 (ml/min per 1.73 m) per year, 95% CI -1.55 to -0.84]. Among SVR patients, recent injection cocaine use was associated with rapid eGFR decline [-2.16 (ml/min per 1.73 m)/year, 95% CI -4.17 to -0.16]. SVR did not reduce the rate of kidney function decline among HCV-HIV co-infected patients. Increased risk of chronic kidney disease in co-infection may not be related to persistent HCV replication but to ongoing injection cocaine use.

Is Visceral Leishmaniasis the same in HIV-coinfected adults?

IntroductionVisceral Leishmaniasis is the most severe form of disease caused by the Leishmania donovani complex, with significant morbidity and mortality in developing countries. Worse outcomes occur among HIV-positive individuals coinfected with Leishmania. It is unclear, however, if there are significant differences on presentation between Visceral Leishmaniasis patients with or without HIV coinfection. MethodsWe reviewed medical records from adult patients with Visceral Leishmaniasis treated at a reference healthcare center in Fortaleza – Ceará, Brazil, from July 2010 to December 2013. Data from HIV-coinfected patients have been abstracted and compared to non-HIV controls diagnosed with Visceral Leishmaniasis in the same period. ResultsEighty one HIV-infected patients and 365 controls were enrolled. The diagnosis in HIV patients took significantly longer, with higher recurrence and death rates. Kala-azar's classical triad (fever, constitutional symptoms and splenomegaly) was less frequently observed in Visceral Leishmaniasis-HIV patients, as well as jaundice and edema, while diarrhea was more frequent. Laboratory features included lower levels of hemoglobin, lymphocyte counts and liver enzymes, as well as higher counts of blood platelets and eosinophils. HIV-infected patients were diagnosed mainly through amastigote detection on bone marrow aspirates and treated more often with amphotericin B formulations, whereas in controls, rK39 was the main diagnostic tool and pentavalent antimony was primarily used for treatment. ConclusionsClinical and laboratory presentation of Visceral Leishmaniasis in HIV-coinfected patients may differ from classic kala-azar, and these differences may be, in part, responsible for the delay in diagnosing and treating leishmaniasis, which might lead to worse outcomes.

Treatment of hepatitis C genotype 1 infection in Germany: effectiveness and safety of antiviral treatment in a real-world setting.

In pivotal studies with direct-acting antivirals (DAAs), rates of sustained virological response in hepatitis C genotype 1 infection are >90%. The objective of this article is to assess real-world safety and effectiveness of DAA treatment in a prospective multicenter registry study. The German Hepatitis C-Registry includes 6606 patients with genotype 1 from 246 centers, treated between February 2014 and June 2016 at the discretion of the physician. A total of 4846 patients completed treatment and follow-up; 51% of these patients were treatment experienced and 28% had liver cirrhosis. Comorbidities were reported in 76% of patients, including HIV co-infection in 8%. SVR12 was 92% with 91% in GT1a and 93% in GT1b. HIV co-infected patients (n = 247) had an SVR12 of 92%. Treatment was discontinued prematurely in 2.5%. In multivariate analysis, SVR12 was dependent on the choice of antiviral regimen (OR 1.33 (1.24-1.43); p < 0.001), negatively associated with presence of liver cirrhosis (OR 0.71 (0.56-0.89); p < 0.003) and positively associated with female gender (OR 1.52 (1.21-1.91); p < 0.001). Data from this real-world registry show SVR12 rates close to those obtained in clinical studies. Discontinuation rates are low, confirming good tolerance of the regimens and good adherence of patients (Trial registration number DRKS00009717, German Clinical Trials Register, DRKS).

The clinical and laboratory features of neurosyphilis in HIV-infected patients: A retrospective study in 92 patients.

Neurosyphilis (NS) is an important component of central nervous system diseases among HIV-infected patients. However, its characteristics are not very clear. A retrospective analysis of clinical and laboratory findings was performed in 92 NS patients with HIV infection from a tertiary hospital in Shanghai, China. The patients had a median age of 38 years and a median CD4 count of 198 cells/μL. In all, 44.6% (41/92) were diagnosed as asymptomatic NS (ANS), 23.9% (22/92) as syphilitic meningitis, 17.4% (16/92) as cerebrovascular NS, and 14.1% (13/92) as parenchymal syphilis. A quarter of patients (23/92) complicated with ocular syphilis (OS), 60.9% (14/23) of which were ANS. The serum tolulized red unheated serum test (TRUST) titers were ≤1:8 in 15 patients (16.3%), 1:16–1:128 in 51 patients (55.4%), and ≥1:256 in 26 patients (28.3%). Sixty-nine patients (75.0%) had both cerebrospinal fluid (CSF) TRUST and Treponema pallidum particle assay reactive. CSF pleocytosis and protein elevation were found in 58.7% and 53.3% of patients, respectively. Syphilitic meningitis was more likely to present with CSF pleocytosis than ANS (P = .001), cerebrovascular NS (P < .001), and parenchymal NS (P < .001). The proportion of patients with CSF elevated protein was lower in ANS group than that in syphilitic meningitis (P = .003), cerebrovascular NS (P = .001), and parenchymal NS groups (P = .025), and was higher in sero-TRUST titers ≤1:8 group than that in 1:16–1:128 (P = .01) and 1:256–1:1024 groups (P = .005).This study revealed that ANS was the most common clinical type of NS in HIV-infected patients, which should be considered in HIV and syphilis co-infection patients without neurologic symptoms, especially in those with OS. Different patterns of NS might have different CSF features which may also vary with sero-TRUST titers.

Cost-effectiveness of hepatitis C screening and treatment linkage intervention in US methadone maintenance treatment programs

BackgroundWe evaluated the cost-effectiveness of a hepatitis C (HCV) screening and active linkage to care intervention in US methadone maintenance treatment (MMT) patients using data from a randomized trial conducted in New York City and San Francisco. MethodsWe used a decision analytic model to compare 1) no intervention; 2) HCV screening and education (control); and 3) HCV screening, education, and care coordination (active linkage intervention). We also explored an alternative strategy wherein HCV/HIV co-infected participants linked elsewhere. Trial data include population characteristics (67% male, mean age 48, 58% HCV infected) and linkage rates. Data from published sources include treatment efficacy and HCV re-infection risk. We projected quality-adjusted life years (QALYs) and lifetime medical costs using an established model of HCV (HEP-CE). Incremental cost-effectiveness ratios (ICERs) are in 2015 US$/QALY discounted 3% annually. ResultsThe control strategy resulted in a projected 35% linking to care within 6 months and 31% achieving sustained virologic response (SVR). The intervention resulted in 60% linking and 54% achieving SVR with an ICER of $24,600/QALY compared to no intervention from the healthcare sector perspective and was a more efficient use of resources than the control strategy. The intervention had an ICER of $76,500/QALY compared to the alternative strategy. From a societal perspective, the intervention had a net monetary benefit of $511,000–$975,600. ConclusionsHCV care coordination interventions that include screening, education and active linkage to care in MMT settings are likely cost-effective at a conventional $100,000/QALY threshold for both HCV mono-infected and HIV co-infected patients.

Treatment of hepatitis C: Results in real life.

Direct-acting antivirals (DAAs) have transformed traditional treatment options for hepatitis C virus (HCV) infection. DAA combinations have been shown to be highly effective in reducing the burden of chronic HCV infection in clinical trials and have been recommended by the European Association for the Study of the Liver (EASL) treatment guidelines. This review examines the results of second-generation DAA combinations in real-life clinical practice in patients with genotypes1-3 and in those co-infected with HIV (real-world data in genotypes 4-6 are rare). Second generation DAAs (sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, sofosbuvir plus velpatasvir, glecaprevir plus pibrentasvir, grazoprevir plus elbasvir) have very high SVR rates and good safety profiles, higher resistance barriers and are more convenient. Real-world data in all 3 genotypes generally support the EASL guidelines and high overall sustained virological response rates are reported with recommended regimens. However, real-world data are only available for sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir. Furthermore, because of the existing level of evidence, it is difficult to define optimal regimens based on real-world data (ie, treatment duration, when to include ribavirin and options for patients with cirrhosis). The real-life challenges of managing HIV-coinfected patients are also discussed showing the additional burden of avoiding drug-drug interactions between DAAs and antiretrovirals.

Interferon-free therapy for treating hepatitis C virus in difficult-to-treat HIV-coinfected patients.

Data regarding the use of all-oral direct-acting antivirals in HIV/hepatitis C virus (HCV)-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognized as predictors of treatment failure. COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain. Data of all HIV/HCV-coinfected patients treated with direct-acting antiviral under real-life conditions were retrospectively collected, and factors associated with treatment success or safety were analysed. Among 515 included patients, 96% were on antiretroviral therapy and 89.5% had an HIV-RNA less than 50 copies/ml. HCV genotype (G) distribution was 47% G-1a, 20% G-4, 14.4% G-1b, and 12.8% G-3. Patients with cirrhosis were 54.2%, and 46% failed to prior HCV-therapies. Overall, 92.8% patients (95% confidence interval: 90.2-94.9) achieved sustained virologic response (SVR12). Cirrhosis was the only factor associated with treatment failure, and SVR12 rate was significantly lower in patients with liver stiffness at least 21 kPa. Adverse events were reported in 36.7%, but only two patients (0.4%) discontinued treatment because of adverse events. The bivariate analysis showed an association between ribavirin use and an increased risk of adverse events (odds ratio 2.84; 95% confidence interval: 1.95-4.1; P ≤ 0.0001). This heterogeneous cohort of coinfected patients showed a high rate of SVR12. Among cirrhotic patients, those with a liver stiffness at least 21 kPa had a higher probability of treatment failure. Ribavirin use seems to increase the appearance of adverse events.

Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

Patients with visceral leishmaniasis (VL)–human immunodeficiency virus (HIV) coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients.

Incidence and predictors of single drug discontinuation according to the presence of HCV coinfection in HIV patients from the ICONA Foundation Cohort Study

To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection.

Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Soeiro C, Tavares A, Castro R. Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature. HIV & AIDS Review. International Journal of HIV-Related Problems. 2018;17(2):146-151. doi:10.5114/hivar.2018.76378. APA Soeiro, C., Tavares, A., & Castro, R. (2018). Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature. HIV & AIDS Review. International Journal of HIV-Related Problems, 17(2), 146-151. https://doi.org/10.5114/hivar.2018.76378 Chicago Soeiro, Cristina, Ana P. Tavares, and Rui Sarmento e Castro. 2018. "Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature". HIV & AIDS Review. International Journal of HIV-Related Problems 17 (2): 146-151. doi:10.5114/hivar.2018.76378. Harvard Soeiro, C., Tavares, A., and Castro, R. (2018). Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature. HIV & AIDS Review. International Journal of HIV-Related Problems, 17(2), pp.146-151. https://doi.org/10.5114/hivar.2018.76378 MLA Soeiro, Cristina et al. "Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature." HIV & AIDS Review. International Journal of HIV-Related Problems, vol. 17, no. 2, 2018, pp. 146-151. doi:10.5114/hivar.2018.76378. Vancouver Soeiro C, Tavares A, Castro R. Hepatitis B reactivation after HCV treatment with sofosbuvir/ledipasvir in a HIV-coinfected patient with previous positive anti-HBs antibody: a case report and a review of literature. HIV & AIDS Review. International Journal of HIV-Related Problems. 2018;17(2):146-151. doi:10.5114/hivar.2018.76378.