The prevalence of antiretroviral drug resistance in patients undergoing routine testing while receiving treatment in the UK is about 50%. Most resistance is against nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, but 25% of patients receiving protease inhibitors (PIs) also have evidence of PI resistance. Although extensive resistance profiles are rare, a proportion of patients present with complex genotypes, which makes treatment selection difficult and vitally important. A resistance profile can be interpreted to provide an indication of the degree of resistance to different drugs and the potential drug options. Factors to bear in mind during treatment selection include phenotypic and genotypic resistance, mutation patterns, numbers and ‘weights’, and the hypersusceptibility and fitness effects of certain mutations. In treatment-experienced patients, physicians should aim for a regimen that combines at least two, preferably three, fully active drugs. In addition to selecting drugs that are predicted to have activity, the relative genetic barrier, cross-resistance potential and support needed to maintain activity in the long term are also key considerations.
•HDV infection is common among HBsAg-positive people worldwide.•Among HBsAg-positive people, estimated HDV prevalence is 4.5% (95% CI 3.6–5.7).•HDV prevalence in HBsAg-positive hepatology clinic attendees is 16.4% (14.6–18.6).•HDV prevalence is higher in people who inject drugs and who have HCV or HIV.•HDV causes an estimated 18% of cirrhosis and 20% of HCC associated with hepatitis B. Background and AimsThere are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among HBsAg-positive people.MethodsWe searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random effects models.ResultsWe included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6–5.7) among all HBsAg-positive people and 16.4% (14.6–18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11–0.25) of the general population, totalling 12.0 (8.7–18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10–26) for cirrhosis and 20% (8–33) for HCC.ConclusionsAn estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precision of burden estimates.Lay summaryWe combined all available studies to estimate how many people with hepatitis B also have hepatitis D, a viral infection that only affects people with hepatitis B. About 1 in 22 people with hepatitis B also have hepatitis D, increasing to 1 in 6 when considering people with liver disease. Hepatitis D may cause about 1 in 6 of the cases of cirrhosis and 1 in 5 of the cases of liver cancer that occur in people with hepatitis B. Hepatitis D is an important contributor to the global burden of liver disease. There are uncertainties about the epidemic patterns of HDV infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among HBsAg-positive people. We searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random effects models. We included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6–5.7) among all HBsAg-positive people and 16.4% (14.6–18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11–0.25) of the general population, totalling 12.0 (8.7–18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with HCV or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10–26) for cirrhosis and 20% (8–33) for HCC. An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precision of burden estimates.
Jose Debes and Shemal Shah highlight the paucity of data from east Africa, one of our major findings. The authors draw attention to a study from Tanzania, where samples that initially tested positive for antibodies against hepatitis D virus by a commercial assay did not test positive on retesting with a second assay.1Winter A Letang E Vedastus Kalinjuma A et al.Absence of hepatitis delta infection in a large rural HIV cohort in Tanzania.Int J Infect Dis. 2016; 46: 8-10Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar The performance of the second assay relative to the first was unknown. Given that the first assay was used widely in the studies included in our analysis without confirmation by a second assay, we elected not to take retesting into account for the study from Tanzania and to maintain consistency with data available from the other studies. Further research is required to determine whether there is a generalisable issue with the specificity of hepatitis D virus antibody testing in Africa. We agree that considerations of assay specificity are important in this setting, as also seen with the detection of antibodies against hepatitis C virus.2King S Adjei-Asante K Appiah L et al.Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV-infected adults in Ghana.J Viral Hepat. 2015; 22: 461-468Crossref PubMed Scopus (15) Google Scholar In the case of hepatitis B virus testing, however, there appears to be an issue of reduced sensitivity, rather than reduced specificity, when using rapid screening tests for HBsAg.3Geretti AM Patel M Sarfo FS et al.Detection of highly prevalent hepatitis B virus coinfection among HIV-seropositive persons in Ghana.J Clin Microbiol. 2010; 48: 3223-3230Crossref PubMed Scopus (73) Google Scholar We are less clear about the assertion that suppression of hepatitis B virus replication with antiviral therapy makes hepatitis D virus positivity less likely. The hepatitis D virus particle comprises an RNA genome, a single hepatitis D virus-encoded antigen, and a lipoprotein envelope provided by hepatitis B virus. Nucleoside and nucleotide analogues inhibit replication of hepatitis B virus, but rarely lead to HBsAg loss. Although long-term suppression of hepatitis B virus replication might possibly also result in the suppression of hepatitis D virus replication, evidence in support of this statement is at best conflicting.4Soriano V Vispo E Sierra-Enguita R et al.Efficacy of prolonged tenofovir therapy on hepatitis delta in HIV-infected patients.AIDS. 2014; 28: 2389-2394Crossref PubMed Scopus (51) Google Scholar, 5Béguelin C Friolet N Moradpour D et al.Impact of tenofovir on hepatitis delta virus replication in the Swiss HIV cohort study.Clin Infect Dis. 2017; 64: 1275-1278Crossref PubMed Scopus (18) Google Scholar It is nonetheless important to emphasise that eradication of hepatitis D virus at the population level must ultimately rely on the implementation of effective policies to reduce hepatitis B virus transmission. Edouard Tuaillon and colleagues describe the use of dried blood spots (DBSs) for the detection of antibodies against hepatitis D virus in a large survey of adult volunteers in Burkina Faso. Consistent with our conclusions,6Stockdale AJ Chaponda M Beloukas A et al.Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis.Lancet Glob Health. 2017; 5: e992-e1003Summary Full Text Full Text PDF PubMed Scopus (76) Google Scholar the authors observed localised clusters of endemicity, and exploration of the risk factors for hepatitis D virus infection in the same population would be of interest. The report indicates that DBS offer a promising tool for obtaining representative measurements of the prevalence of hepatitis D virus. Validation data will increase confidence in the reliability of DBS testing for antibodies against hepatitis D virus. Important technical challenges remain: use of elutes from DBS samples reduces overall testing sensitivity, and whether DBS testing is a suitable method for hepatitis D virus RNA detection in Africa remains to be demonstrated. This online publication has been corrected. The corrected version first appeared at thelancet.com/lancetgh on January 15, 2018 This online publication has been corrected. The corrected version first appeared at thelancet.com/lancetgh on January 15, 2018 AMG reports consultancy and speaker fees from Abbott, AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and ViiV. The University of Liverpool is the recipient of research funds from Bristol-Myers Squibb, Gilead, Janssen, and ViiV for studies of which AMG is the principal investigator. AMG is employed as an expert scientist by Roche Pharma Research and Early Discovery (pRED); Roche pRED has no involvement in the work presented. All other authors declare no competing interests. Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysisFindings suggest localised clusters of hepatitis D virus endemicity across sub-Saharan Africa. Epidemiological data are needed from southern and east Africa, and from patients with established liver disease. Further studies should aim to define the reliability of hepatitis D virus testing methods, identify risk factors for transmission, and characterise the natural history of the infection in the region. Full-Text PDF Open AccessEpidemiological data for hepatitis D in AfricaThe systematic review on the seroprevalence of hepatitis D virus in sub-Saharan Africa by Alexander Stockdale and colleagues1 is a key contribution to the epidemiology of hepatitis D virus infection, and highlights the scarcity of reliable data from the African continent. Most of the studies included in this meta-analysis were based on convenience sampling, and less than half of these studies include a confirmation of hepatitis D virus infection by a molecular test. The Article concludes that there is a need for reliable epidemiological data that are representative of the general population, that there are localised clusters of hepatitis D virus endemicity, and that there is a need for reliable hepatitis D virus testing methods. Full-Text PDF Open AccessEpidemiological data for hepatitis D in AfricaAlexander Stockdale and colleagues (October, 2017)1 describe the epidemiology of hepatitis D virus in Africa, and conclude that the infection is more common in west Africa than in other regions, particularly east Africa. This epidemiological statement is generally known among practising hepatologists and has important implications when screening for hepatitis D virus. However, a few points should be highlighted from the study. Full-Text PDF Open AccessCorrection to Lancet Glob Health 2018; 6: e34Stockdale AJ, Beloukas A, Geretti AM. Epidemiological data for hepatitis D in Africa. Author's reply. Lancet Glob Health 2018; 6: e34—In this Correspondence (January, 2017), Anna Maria Geretti's name was misspelled. This correction has been made as of Jan 15, 2018. Full-Text PDF Open Access
Immunological correlates of AIDS-free survival after human immunodeficiency virus type 1 (HIV-1) infection are largely unknown. Cytotoxic T lymphocyte (CTL) responses are generally believed to be a major component of protective immunity against viral infections. However, the relationship between HIV-1-specific CTL responses and disease progression rate is presently unclear. Here we show in twelve HIV-1-infected individuals that detection of Rev-specific CTL precursors (CTLp) early in the asymptomatic stage, as well as detection of Rev- and Tat-specific CTLp later during follow-up, inversely correlate with rapid disease progression. No such correlation was found for detection of CTLp against Gag, RT or Nef. Further studies are required to determine whether a protective mechanism is indeed the basis of the observed correlation. The data presented are in agreement with the hypothesis that CTL against proteins that are important for early viral transcription and translation are of particular importance in protection from rapid disease progression.
HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA-negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV-positive subjects (three males, two females) were aged 30-46 years, by questionnaire-based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV-infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.
Introduction Urban homeless populations in the UK have been shown to have high rates of active tuberculosis, but less is known about the prevalence of latent tuberculosis infection (LTBI). This study aimed to estimate the prevalence of LTBI among individuals using homeless hostels in London. Methods We performed a cross-sectional survey with outcome follow-up in homeless hostels in London. Our primary outcome was prevalence of LTBI. Recruitment for the study took place between May 2011 and June 2013. To estimate an LTBI prevalence of 10% with 95% CIs between 8% and 13%, we required 500 participants. Results 491/804 (61.1%) individuals agreed to be screened. The prevalence of LTBI was 16.5% (81/491; 95% CI 13.2 to 19.8). In UK-born individuals, a history of incarceration was associated with increased risk of LTBI (OR 3.49; 95% CI 1.10 to 11.04; P=0.018) after adjusting for age, length of time spent homeless and illicit drug use. Of the three subjects who met English treatment guidelines for LTBI at the time of the study, none engaged with services after referral for treatment. Prevalence of past hepatitis B infection was 10.4% (51/489; 95% CI 7.7 to 13.1), and 59.5% (291/489; 95% CI 55.1 to 63.9) of individuals were non-immune. Prevalence of current hepatitis C infection was 10.4% (51/489; 95% CI 7.8 to 13.1). Conclusions This study demonstrates the high prevalence of LTBI in homeless people in London and the associated poor engagement with care. There is a large unmet need for LTBI and hepatitis C infection treatment, and hepatitis B vaccination, in this group.
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