Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: a literature review

The effectiveness of combination antiretroviral therapy (cART) continues to improve as treatment choices expand with the development of new antiretroviral agents and regimens. However, the successful long-term treatment of HIV/AIDS is under threat from the emergence of drug-resistant strains to multiple agents and entire drug classes.     

Decompensated cirrhosis-related admissions in a large urban hospital in Uganda: prevalence,clinical and laboratory features and implications for planning patient management

Background

Cirrhosis-related complications are a major cause of morbidity and mortality in areas where its risk factors are endemic.

Objective

We determined the prevalence of decompensated cirrhosis among patients on the gastroenterology service of Mulago Hospital and described the clinical and laboratory features of these patients.

Methods

All patients admitted to the unit were assessed and their diagnosis documented. Patients with cirrhosis had clinical features of decompensation recorded. History of alcohol consumption was taken and testing for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) performed.

Results

Between September 2010 and January 2011, we enrolled 482 patients. The majority (53.7%) were male, overall median age 38 years. Decompensated cirrhosis was diagnosed in 85 (17.6%) patients. Of the 85 patients, 47 (55.3%) gave a history of alcohol intake, HBsAg was positive in 23 (27.1%) and anti-HCV in 3 (3.5%). Decompensation was defined by ascites among 81 (95.3%) patients, variceal bleeding in 31 (36.5%), encephalopathy in 20 (23.5%).

Conclusion

Cirrhosis is common in Mulago hospital presenting mainly with ascites and variceal bleeding. Aside from controlling causes of liver diseases, especially alcohol and hepatitis B virus infection, in the interim it is necessary to manage complications in patients who already have cirrhosis.     

A Case report: Herpes zooster IRIS in pregnancy

Pregnant women are increasingly being initiated on antiretroviral therapy either as part of prevention of mother to child transmission of HIV or as purely highly active antiretroviral therapy.In this case report, we describe a 26 year old woman who was 28 weeks pregnant and who presented after 4 weeks of initiation of antiretroviral therapy with a herpes zoster eruption and how the case was managed at the Infectious Diseases Institute, Kampala, Uganda.     

Treatment of chronic hepatitis B virus infection in resource‐constrained settings: expert panel consensus

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource‐constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV‐related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20–30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV‐infected persons in Africa who are co‐infected with HBV. Progressive liver disease has been shown to occur in co‐infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV‐infected persons should be screened for HBV infection; HIV/HBV co‐infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource‐constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource‐constrained settings.     

Low frequency of liver enzyme elevation in HIV-infected patients attending a large urban treatment centre in Uganda

Liver enzyme elevations among patients on antiretroviral therapy (ART) were determined by prospectively evaluating aspartate aminotransferase (AST) data in a cohort of patients in Kampala over 36 months. A proportion of patients had hepatitis B virus (HBV) status determined. Hepatotoxicity was graded I to IV according to the AIDS Clinical Trial Group criteria. Of 546 patients, 377 (69%) were women; overall median baseline CD4+ T-cell was 97/μL (interquartile range [IQR] 20-164). Hepatitis B surface antigen (HBsAg) was detected in 42 (9%) of 470 persons. ART included lamivudine, with either nevirapine and d4T (74%) or efavirenz and AZT (26%). Median (IQR) AST level at baseline was 35 (27, 53 IU/L). Over 36 months, only eight patients had grade III AST elevation. Neither HBsAg nor ART regimen influenced AST levels. Male gender and CD4+ change from baseline were correlated with AST elevation. Patients with HIV/HBV co-infection were not at an increased risk of AST elevation, which occurred uncommonly in this setting.     

The liver in HIV in Africa

As access to antiretroviral therapy improves across the African continent, liver disease is emerging as an important cause of morbidity and mortality among HIV-infected individuals. Although coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV), along with highly active antiretroviral therapy (HAART)-induced hepatotoxicity appear to be the major causes of liver disease in this population, other diseases endemic to Africa with hepatic manifestations are influenced by HIV infection as well. In this review we present the available data on liver disease in HIV-infected populations in Africa and discuss relevant data from the rest of the world. In addition, we highlight important areas for further study.     

Splanchnic venous thrombosis driven by a constitutively activated JAK2 V617F philadelphia-negative myeloproliferative neoplasm: a case report

Introduction

Splanchnic venous thrombosis (SVT) has varied etiology with Philadelphia-negative myeloproliferative neoplasms (MPNs) being the most frequent underlying prothrombotic factor. Hematological indices often remain within normal range because of portal hypertension and its sequelae, causing diagnostic challenges. The high frequency of JAK2 mutation among patients with SVT reinforces the diagnostic utility of JAK2V617F testing.

Case report

We report a case of a 62-year-old black man with progressive abdominal swelling and features of decompensated chronic liver disease found to have SVT-portal vein thrombosis and how JAK2 V617F was useful in unmasking an underlying myeloproliferative neoplasm.

Conclusion

A high index of suspicion for an underlying prothrombotic factor is critical for patients presenting with thrombosis in unusual sites. This is useful in prognostic stratification and patient outcomes. JAK2 mutation screening is now part of the standard diagnostic workup in SVT.     

Validity of the rapid strip assay test for detecting HBsAg in patients admitted to hospital in Uganda

Commercially available rapid strip assays (RSAs) for hepatitis B surface antigen (HBsAg) are used for most routine clinical testing in sub‐Saharan Africa. This study evaluated the validity of RSA and a more sophisticated enzyme immunoassay (EIA) with confirmation by nucleic acid testing (NAT) in hospitalized patients in Uganda. Sera from 380 consecutive patients collected and tested for HBsAg and anti‐HIV in Kampala, Uganda by RSA were sent frozen to Dallas for EIA including HBsAg, total anti‐hepatitis B core, hepatitis B e antigen, and anti‐HIV. NAT was performed on all HBsAg‐positives and on a random sample of 102 patients that were HBsAg‐negative by both assays. Overall, 31 (8%) were HBsAg positive by RSA while 50 (13%) were HBsAg‐positive by EIA; 26 were concordant between the two assays. Of 55 HBsAg‐positive patients, nearly all showed detectable serum hepatitis B virus (HBV) DNA by bDNA (46) or PCR (4) assay. The 26 patients who were HBsAg positive by both EIA and RSA had significantly higher median serum HBV DNA levels than the 24 patients who were HBsAg positive by EIA alone. An additional 12/102 (12%) HBsAg negative patients had very low serum HBV DNA levels by NAT. Several differences in expected results of serologic testing were observed in this large series of African patients. RSA HBsAg testing is less sensitive than EIA; even EIA failed to detect all HBV DNA positive sera. A more complex testing protocol than RSA alone will be needed in Africa to improve patient care. J. Med. Virol. 82:1334–1340, 2010. © 2010 Wiley‐Liss, Inc.