Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data.

BACKGROUND: Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. OBJECTIVES: To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. METHODS: We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. RESULTS: In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). CONCLUSIONS: Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN.

Point of care HbA1c level for diabetes mellitus management and its accuracy among tuberculosis patients: a study in four countries.

BACKGROUND: Diabetes mellitus (DM) is common among tuberculosis (TB) patients and often undiagnosed or poorly controlled. We compared point of care (POC) with laboratory glycated haemoglobin (HbA1c) testing among newly diagnosed TB patients to assess POC test accuracy, safety and acceptability in settings in which immediate access to DM services may be difficult. METHODS: We measured POC and accredited laboratory HbA1c (using high-performance liquid chromatography) in 1942 TB patients aged 18 years recruited from Peru, Romania, Indonesia and South Africa. We calculated overall agreement and individual variation (mean ± 2 standard deviations) stratified by country, age, sex, body mass index (BMI), HbA1c level and comorbidities (anaemia, human immunodeficiency virus [HIV]). We used an error grid approach to identify disagreement that could raise significant concerns. RESULTS: Overall mean POC HbA1c values were modestly higher than laboratory HbA1c levels by 0.1% units (95%CI 0.1-0.2); however, there was a substantial discrepancy for those with severe anaemia (1.1% HbA1c, 95%CI 0.7-1.5). For 89.6% of 1942 patients, both values indicated the same DM status (no DM, HbA1c <6.5%) or had acceptable deviation (relative difference <6%). Individual agreement was variable, with POC values up to 1.8% units higher or 1.6% lower. For a minority, use of POC HbA1c alone could result in error leading to potential overtreatment (n = 40, 2.1%) or undertreatment (n = 1, 0.1%). The remainder had moderate disagreement, which was less likely to influence clinical decisions. CONCLUSION: POC HbA1c is pragmatic and sufficiently accurate to screen for hyperglycaemia and DM risk among TB patients.

Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. METHODS: HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. RESULTS: A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. CONCLUSIONS: HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype.

Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in the EuroSIDA study.

OBJECTIVES: The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe. METHODS: Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in the study. cART was defined as d4T-containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T. RESULTS: A total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19-20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23-29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16-19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80-0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17-9.98) versus other European regions and HIV RNA > 400 copies/mL (aIRR 3.11; 95% CI 1.60-6.02) versus HIV RNA < 400 copies/mL. CONCLUSIONS: d4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV-positive patients are aware of the potential harmful effects associated with d4T.

Temporal changes and regional differences in treatment uptake of hepatitis C therapy in EuroSIDA.

OBJECTIVES: All HIV/hepatitis C virus (HCV)-coinfected patients with chronic HCV infection and ≥ F2 fibrosis should be considered for HCV therapy. This study aimed to determine the rate of HCV treatment uptake among coinfected patients in Europe. METHODS: EuroSIDA patients with viraemic HCV infection were included in the study. Poisson regression was used to identify temporal changes and regional differences in HCV treatment uptake. RESULTS: A total of 1984 patients were included in the study, with a median follow-up time of 168 months [interquartile range (IQR) 121-204 months]. To date, 501 (25.3%) HIV/HCV-coinfected patients have received HCV therapy. Treatment incidence rose from 0.33 [95% confidence interval (CI) 0.16-0.50] per 100 person-years of follow-up (PYFU) in 1998 to 5.93 (95% CI 4.49-7.38) in 2007, falling to 3.78 (95% CI 2.50-5.07) in 2009. After adjustment, CD4 cell count > 350 cells/µL [incidence rate ratio (IRR) 1.33 (95% CI 1.06-1.67) vs. CD4 count 200-350 cells/µL] and ≥F2 liver fibrosis [IRR 1.60 (95% CI 1.14-2.25; P = 0.0065) vs. < F2 fibrosis] were predictors of anti-HCV treatment initiation. However, 22% of patients who remain untreated for HCV, with fibrosis data available, had ≥F2 fibrosis and should have been considered for treatment, while only 36% of treated patients had ≥F2 fibrosis. CONCLUSIONS: Although treatment incidence for HCV has increased, there remain a large proportion of patients indicated for treatment who have yet to be treated.

Stability of hepatitis C virus (HCV) RNA levels among interferon-naïve HIV/HCV-coinfected individuals treated with combination antiretroviral therapy.

OBJECTIVES: Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. High HCV RNA levels have been associated with poor treatment response. This study aimed to examine the natural history of HCV RNA in chronically HCV/HIV-coinfected individuals. METHODS: Mixed models were used to analyse the natural history of HCV RNA changes over time in HIV-positive patients with chronic HCV infection. RESULTS: A total of 1541 individuals, predominantly White (91%), male (73%), from southern (35%) and western central Europe (23%) and with HCV genotype 1 (58%), were included in the analysis. The median follow-up time was 5.0 years [interquartile range (IQR) 2.8 to 8.3 years]. Among patients not on combination antiretroviral therapy (cART), HCV RNA levels increased by a mean 27.6% per year [95% confidence interval (CI) 6.1-53.5%; P = 0.0098]. Among patients receiving cART, HCV RNA levels were stable, increasing by a mean 2.6% per year (95% CI -1.1 to 6.5%; P = 0.17). Baseline HCV RNA levels were 25.5% higher (95% CI 8.8 to 39.1%; P = 0.0044) in individuals with HCV genotype 1 compared with HCV genotypes 2, 3 and 4. A 1 log HIV-1 RNA copies/mL increase in HIV RNA was associated with a 10.9% increase (95% CI 2.3 to 20.2%; P = 0.012) in HCV RNA. CONCLUSIONS: While HCV RNA levels increased significantly in patients prior to receiving cART, among those treated with cART HCV RNA levels remained stable over time.

Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients.

OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0-5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1-3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5-1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31-48) among patients with an HCI score of 0, to 9% (95%CI 6-13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64-0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.