Hepatitis C Screening in People with Human Immunodeficiency Virus: Lessons Learned from Syphilis Screening

Background.  

The incidence of hepatitis C virus (HCV) infection is increasing in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). New guidelines recommend annual screening for HCV, similar to recommendations for syphilis screening with rapid plasma reagin (RPR). 

Methods. 

This study compares the frequency of repeat HCV antibody (Ab) testing to repeat RPR testing in a retrospective chart review of 359 HCVAb-negative people living with HIV (PLWH) observed in an Infectious Diseases clinic. Patients were classified into risk groups based on sexual risk factors. 

Results.

Although 85% of PLWH had repeat syphilis screening, less than two thirds had repeat HCVAb screening. The MSM status was associated with increased HCVAb and RPR testing (adjusted odds ratio, 2.6 and 5.9, respectively). Seven persons had incident HCV infection: 3 were MSM, and 4 had symptoms or abnormal laboratory results to prompt testing. 

Conclusions.

Failure to find incident HCV infection in PLWH represents missed opportunities to cure HCV infection and prevent progressive liver disease. Further quality improvement studies are necessary to develop physician-focused interventions to increase HCV screening rates in PLWH.

Full article at:   https://goo.gl/hCydqw

By:  Wurcel AG1, Chen DD2, Fitzpatrick RE2, Grasberger PE2, Kirshner CH2, Anderson JE2, Chui KK2, Knox TA2.

• 1Department of Geographic Medicine and Infectious Diseases, Tufts Medical Center; Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts.
• 2Department of Public Health and Community Medicine , Tufts University School of Medicine , Boston, Massachusetts. 
• Open Forum Infect Dis. 2016 Feb 12;3(1):ofv215. doi: 10.1093/ofid/ofv215. eCollection 2016.

More at:  https://twitter.com/hiv insight

And: http://twitter.com/Prison Health

National Trend and Characteristics of Acute Hepatitis C among HIV-Infected Individuals: A Matched Case-Control Study—Taiwan, 2001–2014

Hepatitis C virus (HCV) infection has been increasingly recognized among HIV-infected men who have sex with men (MSM) worldwide. We investigated the trend of and factors associated with acute hepatitis C (AHC) among HIV-infected individuals in Taiwan.

The National Disease Surveillance System collects characteristics of AHC, HIV, syphilis, and gonorrhea cases through mandatory reports and patient interviews. Reported AHC patients in 2014 were interviewed additionally on sexual and parenteral exposures. Information on HCV genotypes were collected from the largest medical center serving HIV-infected Taiwanese. We defined an HIV/AHC case as a documented negative HCV antibody test result followed within 12 months by a positive test in a previously reported HIV-infected individual. Each case was matched to two HIV-infected, non-AHC controls for age, age of HIV diagnosis, sex, transmission route, HIV diagnosis date, and county/city. Conditional logistic regression was used to identify associated characteristics.

During 2001–2014, 93 of 6,624 AHC reports were HIV/AHC cases; the annual case count increased from one in 2009 to 34 in 2014. All were males (81 [87%] MSM) aged 21–49 years with AHC diagnosed 2–5,923 days after HIV diagnoses. Sixty-eight (73%) lived in the Taipei metropolitan area. Detected HCV genotypes were 2a (n = 6), 1b (n = 5), 1b + 2a (n = 1) and 2b (n = 1). Among 28 HIV/AHC patients interviewed in 2014, 13 (46%) reported engaging in unprotected sex ≤3 months before AHC diagnosis. Seventy-nine HIV/AHC cases were matched to 158 controls. HIV/AHC was associated with recent syphilis (adjusted odds ratio [aOR], 10.9; 95% confidence interval [CI], 4.2–28.6) and last syphilis >6 months (aOR, 2.9; 95% CI, 1.2–6.9).

HIV/AHC cases continued to increase particularly among sexually active HIV-infected MSM with a syphilis diagnosis in northern Taiwan. We recommend surveillance of associated behavioral and virologic characteristics and HCV counseling and testing for HIV-infected men in Taiwan.

Below:  Proportion of HIV/AHC cases among AHC cases with documented HCV seroconversion, Taiwan, 2001–2014

Below:  Trend of HIV/AHC cases by population at risk, Taiwan, 2001–2014

Below:  Number of HIV/AHC cases in each county and city, Taiwan, 2001–2014 

Numbers in the map indicate numbers of HIV/AHC cases in each city or county

Full article at: http://goo.gl/0HFNZa

By: 

Yi-Chun Lo, Jen-Hsiang Chuang

Taiwan Centers for Disease Control, Taipei, Taiwan

Yi-Chun Lo, Hsin-Yun Sun, Chien-Ching Hung

Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Mao-Song Tsai

Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

  

More at:  https://twitter.com/hiv_insight

Independent Predictors of Tuberculosis Mortality in a High HIV Prevalence Setting: A Retrospective Cohort Study

Identifying those at increased risk of death during TB treatment is a priority in resource-constrained settings. We performed this study to determine predictors of mortality during TB treatment.

We performed a retrospective analysis of a TB surveillance population in a high HIV prevalence area that was recorded in ETR.net (Electronic Tuberculosis Register). Adult TB cases initiated TB treatment from 2007 through 2009 in Khayelitsha, South Africa. Cox proportional hazards models were used to identify risk factors for death (after multiple imputations for missing data). Model selection was performed using Akaike’s Information Criterion to obtain the most relevant predictors of death.

Of 16,209 adult TB cases, 851 (5.3 %) died during TB treatment. In all TB cases, advancing age, co-infection with HIV, a prior history of TB and the presence of both pulmonary and extra-pulmonary TB were independently associated with an increasing hazard of death. In HIV-infected TB cases, advancing age and female gender were independently associated with an increasing hazard of death. Increasing CD4 counts and antiretroviral treatment during TB treatment were protective against death. In HIV-uninfected TB cases, advancing age was independently associated with death, whereas smear-positive disease was protective.

We identified several independent predictors of death during TB treatment in resource-constrained settings. Our findings inform resource-constrained settings about certain subgroups of TB patients that should be targeted to improve mortality during TB treatment.

Below:  Kaplan Meier plot showing cumulative mortality during TB treatment: (1) overall mortality, and (2) mortality by HIV status

Full article at: http://goo.gl/tt4txn

By: Dominique J. Pepper¹², Michael Schomaker³, Robert J. Wilkinson¹⁴⁵, Virginia de Azevedo⁶ and Gary Maartens^17*

¹Department of Medicine, University of Cape Town, Anzio Road, Cape Town 7925, South Africa

²Critical Care Medicine Department, National Institutes of Health, 10 Center Drive, Bethesda, USA

³Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Anzio Road, Cape Town 7925, South Africa

⁴Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa

⁵Department of Medicine, Imperial College, London W2 1PG, UK

⁶City Health, Cape Town, South Africa

⁷Division of Pharmacology, Groote Schuur Hospital, Anzio Road, Cape Town 7925, South Africa

  

More at:  https://twitter.com/hiv_insight

Association of Cervical Precancer with Human Papillomavirus Types Other Than 16 among HIV Co-Infected Women

HIV seropositive women face high risk for infection with oncogenic types of human papillomaviruses (oncHPV), abnormal Pap tests and precancer, but cervical cancer risk is only modestly increased. HPV16 is highly oncogenic but only weakly associated with HIV-status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer.

To assess whether the under-representation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers.

HIV seropositive and seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). DNA from >40 HPV types was detected by PCR in cervicovaginal lavage specimens obtained at the visit at which CIN3+ was diagnosed.

HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3+ but only 44 (29%) of 154 HIV-seropositive CIN3+ (P=0.01). The lower prevalence of HPV16 in CIN3+ among HIV seropositive women persisted after controlling for covariates (O.R. 0.25, 95% C.I. 0.08, 0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3+ (OR=1.02, 95% C.I. 0.53, 1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV seropositive vs seronegative women with CIN3+ (OR=3.9, 95% C.I. 1.3, 11.8).

The previously demonstrated increase in CIN3+ incidence among HIV seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV seropositive women.

Via: http://goo.gl/KMVxYz  Purchase full article at: http://goo.gl/Gc6i01

By: Massad LS1, Xie X2, Burk RD2, D'Souza G3, Darragh TM4, Minkoff H5, Colie C6, Burian P7, Palefsky J8, Atrio J2, Strickler HD2.

• 1Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO. 
• 2Albert Einstein College of Medicine, Bronx, NY.
• 3Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
• 4Departments of Pathology and Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA.
• 5Maimonides Medical Center, Brooklyn, NY.
• 6Georgetown University, Washington, DC.
• 7Los Angeles County-University of Southern California Medical Center, Los Angeles, CA.
• 8University of California, San Francisco, CA. 

More at:  https://twitter.com/hiv_insight

The Prevalence & Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012

Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross-sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturer’s instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.4±7.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV‏ positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended.

Table 1

Main characteristics of HIVinfected individuals with positive HBs Ag according to delta status

Variable	All HBsAg patients	HDV Abpositive	HDV Abnegative	P value
Number	178	35 (19.7%)	143 (80.3%)	-
Median age (years)	34 (2262)	38 (3062)	37 (2258)	0.045
Marital status	29	6 (17%)	23 (15.4%)	0.9
Unsafe sexual contact	40	6 (17.1%)	34 (23.7%)	0.64
Intravenous drug use	68	15 (42.9%)	53 (37%)	0.8
History of blood transfusion	9	7 (20%)	2 (1.4%)	0.004
History of being imprisoned	69	25 (71.4%)	44 (30.7%)	0.01
ALT level (IU/L)	13.6±8.8	13.2±5.5	13.7±9.4	0.95
AST level (IU/L)	9.2±6.2	8.8±3.7	9.3±6.6	0.92
Median CD4 count (cells/uL)	281	276	289	0.47

Read more at:  http://ht.ly/Sv37y 

By: Mohammad Motamedifar, PhD,1,2 Mohammad Taheri, MSc,2 Kamran Bagheri Lankarani, MD,3 Mina Gholami, BC,2Mahmood Amini Lari, MD,1 Hossein Faramarzi, MD,1 and Jamal Sarvari, PhD2

²Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

³

1Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran

2Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3Health Policy Research Center (HPRC), School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

1Shiraz HIV/AIDS Research Center (SHARC), Shiraz University of Medical Sciences, Shiraz, Iran

Local Perceptions of Causes of Death in Rural South Africa: A Comparison of Perceived and Verbal Autopsy Causes of Death

Below:  Concordance (log-log scale) between CSMF determined by VA and respondent reports, in relation to the line of equivalence, for 6,721 deaths in the Agincourt HDSS, South Africa. CSMF=cause-specific mortality fractions; VA= verbal autopsy.

Agreement between informant-perceived and VA-derived causes of death at the individual level was limited, but varied substantially by cause of death. However, agreement at the population level, comparing cause-specific mortality fractions was higher, with the notable exception of bewitchment as a cause. More recent deaths, those in adults aged 15–49 years, deaths outside the home, and those associated with external causes showed higher concordance with InterVA.

Overall, informant perception of causes of death was limited, but depended on informant characteristics and causes of death, and to some extent involved non-biomedical constructs. Understanding discordance between perceived and recognised causes of death is important for public health planning; low community understanding of causes of death may be detrimental to public health. These findings also illustrate the importance of using rigorous and standardised VA methods rather than relying on informants’ reported causes of death.

Read more at:   http://ht.ly/R2xC1 HT @uniofgothenburg

A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study

Below:  Cumulative incidence of active tuberculosis disease over 5 years in a cohort of HIV-infected adults (N = 772)

Below:  Kaplan-Meier curve of HIV-infected patients who developed active tuberculosis disease by interferon-gamma release assay (IGRA) status, excluding 31 subjects with indeterminate results (N = 741).

Below:  Kaplan-Meier curve to development of active tuberculosis disease by composite risk factor combining high HIV viral load of greater than 100,000 copies per mL, CD4 cell count and interferon-gamma release assay (IGRA)(N = 772).

Below:  A multivariable algorithm to predict risk of active tuberculosis in people with HIV infection using a composite risk factor of HIV viral load, CD4 cell count and interferon-gamma release assay (IGRA) result.

Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49–15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52–24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587–0.798) for the study cohort and 0.792 (95% CI: 0.776–0.808) and 0.766 in the 2 validation cohorts.

A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary exposure of low-risk patients to drug toxicity and simultaneously, reduce the burden of universal treatment on the healthcare system.

Read more at:   http://goo.gl/0XOsvZ MT @PLOSONE 

Rapid Microbiological Screening for Tuberculosis in HIV-Positive Patients on the First Day of Acute Hospital Admission by Systematic Testing of Urine Samples Using Xpert MTB/RIF: Prospective Cohort in South Africa

Below:  Tuberculosis (TB) diagnoses made by Xpert from urine and sputum samples collected in the first 24 h of hospital admission. Venn diagrams show diagnostic yields as proportions of (a) total TB diagnoses (n = 139), (b) TB diagnoses in patients with CD4 cell counts >100 cells/μL (n = 64) and (c) TB diagnoses in patients with CD4 cell counts ≤100 cells/μL (n = 74). Note: the CD4 cell count result was missing for one patient with TB

Below:  Yields of total tuberculosis (TB) diagnoses from all clinical samples collected at any time during hospital admission. Yields of TB diagnoses made by testing urine samples (using Xpert) collected on admission compared with the yield from all sputum samples (using either Xpert and/or culture) and all other non-respiratory samples (using culture). Venn diagrams show yields as proportions of (a) all TB diagnoses (n = 139), (b) TB diagnoses in patients with CD4 cell counts >100 cells/μL (n = 64) and (c) TB diagnoses in patients with CD4 cell counts ≤100 cells/μL (n = 74). Note: the CD4 cell count result was missing for one patient with TB

Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1–37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001).

The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.

Read more at:  http://ht.ly/QURcl HT @LSHTMpress 

Molecular Characterisation of Hepatitis B Virus in HIV-1 Subtype C Infected Patients in Botswana

Below:  Maximum likelihood phylogenetic tree of Botswana sequences and Genbank HBV references. References names start with subgenotype, accession number and country whereas Botswana genotypes start with MA. The numbers at the nodes represent the percentages of the bootstrap values (1000 replicates)

Of the 81 samples included, 70 (86 %) samples were successfully genotyped. Genotype A was found in 56 (80 %) participants, D in 13 (18.6 %), and 1 (1.4 %) was genotype E. Escape mutations previously linked with failure of diagnosis or escaping active vaccination and passive immunoglobulin therapy were detected in 12 (17.1 %) participants at positions 100, 119, 122, 123, 124, 126, 129, 130, 133, 134 and 140 of the S ORF. Genotypes and escape mutations were not significantly associated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST platelet ratio index (APRI).

Genotypes A, D and E were found in this cohort of HIV coinfected patients in Botswana, consistent with the findings from the sub-Saharan Africa region. Some escape mutations which have previously been associated with diagnosis failure, escaping vaccine and immunoglobulin therapy were also observed and are important in guiding future policies related to vaccine implementation, therapeutic guidelines, and diagnostic guidelines. They are also important for identifying patients who are at an increased risk of disease progression and to choose optimal therapy. Future research should focus on determining the clinical significance of the different HBV genotypes and mutations found in this population.

Read more at:   http://ht.ly/QR8Ut  HT @HarvardAIDS

Diverse origins of hepatitis C virus in HIV co-infected men who have sex with men in Hong Kong

Below:  Association between HCV and HIV diagnoses by year and HCV genotypes

We retrospectively examined 24 HIV-positive MSM with acute HCV infection diagnosed between 2009 and 2014 in Hong Kong. Detection and molecular characterization of HCV was successfully performed in 22 (91.7 %) patients. Genotype 3a was the most prevalent as identified in 14 (63.6 %) MSM, followed by 1a in 4 (18.2 %), 6a in 2 (9.1 %), and 1each (4.5 %) for 1b and 2a. The high prevalence of genotype 3a in MSM was in stark contrast to its rarity among HCV infected injection drug users (IDU) in Hong Kong. Phylogenetic analyses revealed a monophyletic HCV-3a cluster composing of MSM without injection history, and a homologous pair with HCV-6a genotype. There was otherwise no temporal or genetic clustering of the corresponding HIV sequences.

The origin of sexually acquired acute HCV infections in HIV-positive MSM was diverse and not directly linked with local IDU. The transmission dynamics of HIV and HCV infections in MSM in Hong Kong were evidently unrelated.

Read more at:   http://ht.ly/QGoaP HT @CUHK 

Early Mortality during Initial Treatment of Tuberculosis in Patients Co-Infected with HIV at the Yaoundé Central Hospital, Cameroon: An 8-Year Retrospective Cohort Study (2006-2013)

Below:  Kaplan-Meier survival curve of cumulative survival over time during tuberculosis treatment of patients co-infected with HIV

The 99 patients enrolled had a mean age of 39.5 (standard deviation 10.9) years and 53% were male. Patients were followed for 276.3 person-months of observation (PMO). Forty nine patients were died during intensive phase of TB treatment. Death incidence during the intensive phase of TB treatment was 32.2 per 100 PMO. Having a non-AIDS comorbidity (aOR 2.47, 95%CI 1.22-5.02, p = 0.012), having extra-pulmonary TB (aOR 1.89, 95%CI 1.05-3.43, p = 0.035), and one year increase in duration of known HIV infection (aOR 1.23, 95%CI 1.004-1.49) were independently associated with death during the intensive phase of TB treatment.

Mortality incidence during intensive phase of TB treatment was high among TB/HIV co-infected patients during TB treatment; and strongly associated with extra pulmonary TB suggesting advanced stage of immunosuppression and non-AIDS comorbidities. Early HIV diagnosis and care and good management of non-comorbidities can reduce this incidence.

Via:   http://goo.gl/jrtcjH HT @UCT_news