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. 

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Does Antiretroviral Therapy Reduce HIV-Associated Tuberculosis Incidence to Background Rates? A National Observational Cohort Study From England, Wales & Northern Ireland

Whether the incidence of tuberculosis in HIV-positive people receiving long-term antiretroviral therapy (ART) remains above background population rates is unclear. We compared tuberculosis incidence in people receiving ART with background rates in England, Wales, and Northern Ireland.

We analysed a national cohort of HIV-positive individuals linked to the national tuberculosis register. Tuberculosis incidence in the HIV-positive cohort (2007-11) was stratified by ethnic origin and time on ART and compared with background rates (2009). Ethnic groups were defined as follows: the black African group included all individuals of black African origin, including those born in the UK and overseas; the white ethnic group included all white individuals born in the UK and overseas; the south Asian group included those of Indian, Pakistani, and Bangladeshi origin, born in the UK and overseas; and the other ethnic group included all other ethnic origins, including black Afro-Caribbeans.

The HIV-positive cohort comprised 79 919 individuals, in whom there were 1550 incident cases in 231 664 person-years of observation (incidence 6·7 cases per 1000 person-years). Incidence of tuberculosis in the HIV-positive cohort was 13·6 per 1000 person-years in black Africans and 1·7 per 1000 person-years in white individuals. Incidence of tuberculosis during long-term ART (≥5 years) in black Africans with HIV was 2·4 per 1000 person-years, similar to background rates of 1·9 per 1000 person-years in this group (rate ratio 1·2, 95% CI 0·96-1·6; p=0·083); but in white individuals with HIV on long-term ART the incidence of 0·5 per 1000 person-years was higher than the background rate of 0·04 per 1000 person-years (rate ratio 14·5, 9·4-21·3; p<0·0001). The increased incidence relative to background in white HIV-positive individuals persisted when analysis was restricted to person-time accrued on ART with CD4 counts of at least 500 cells per μL and when white HIV-positive individuals born abroad were excluded.

Tuberculosis incidence is unacceptably high irrespective of HIV status in black Africans. In white individuals with HIV, tuberculosis incidence is significantly higher than background rates in white people despite long-term ART. Expanded testing and treatment for latent tuberculosis infection to all HIV-infected adults, irrespective of ART status and CD4 cell count, might be warranted.

Via: http://goo.gl/3IOp4z  Purchase full article at: http://goo.gl/SRMAeE

By: Gupta RK1, Rice B2, Brown AE2, Thomas HL3, Zenner D4, Anderson L3, Pedrazzoli D5, Pozniak A6, Abubakar I7, Delpech V2, Lipman M8.

• 1Division of Medicine, University College London, London, UK; HIV/STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK
• 2HIV/STI Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
• 3TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK.
• 4TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK; Centre for Infectious Disease Epidemiology, University College London, London, UK.
• 5TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
• 6Chelsea & Westminster Hospitals NHS Foundation Trust, London, UK.
• 7TB Section, Centre for Infectious Disease Surveillance and Control, Public Health England, London, UK; MRC Clinical Trials Unit and Centre for Infectious Disease Epidemiology, University College London, London, UK.
• 8Division of Medicine, University College London, London, UK. 

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Prevalence & Correlates of HCV Monoinfection & HIV & HCV Coinfection among Persons Who Inject Drugs in Vietnam

Vietnam bears a high burden of hepatitis C virus (HCV) and HIV infection among persons who inject drugs (PWID). The high prevalence of HCV and HIV occurs in a context of stigma and limited preventive interventions for PWID.

This study aims to estimate the prevalence of HCV, HIV, and HIV/HCV coinfection among PWID and to explore their associations with lifetime injection behaviors.

A total of 1434 PWID were recruited from the Thai Nguyen Province of Vietnam between 2005 and 2007. Participants responded to a structured questionnaire and provided blood samples at baseline. A cross-sectional analysis of data collected at baseline was carried out. Factors associated with HCV monoinfection and HIV/HCV coinfection were evaluated by multinomial logistic regression.

The prevalences of HIV and HCV were 35.1 and 88.8%, respectively, and the prevalences of HIV/HCV coinfection and HCV monoinfection were 34.8 and 53.9%, respectively. After adjusting for confounders in multivariate analysis, ever reusing a syringe and needle was found to be significantly associated with HIV monoinfection and HIV/HCV coinfection. Ever sharing diazepam or novocaine was also found to be significantly associated with HIV monoinfection and HIV/HCV coinfection.

Our findings demonstrate a high burden of HIV and HCV infection among PWID in Vietnam. Lifetime injection behaviors, including sharing of diazepam or novocaine, may account for the high prevalence of HIV and HCV. Improving prevention and ensuring access to care remain critically important for this vulnerable population.

Via:  http://ht.ly/SASgJ Purchase full article at: http://goo.gl/6UrXVl

By: Zhang L1, Celentano DD, Le Minh N, Latkin CA, Mehta SH, Frangakis C, Ha TV, Mo TT, Sripaipan T, Davis WW, Quan VM, Go VF.

• 1Departments of aEpidemiology bHealth, Behavior and Society cBiostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland dDepartment of Health Behavior, UNC Gillings School of Global Public Health, Chapel Hill, North Carolina, USA eThai Nguyen Center for Preventive Medicine, Thai Nguyen, Vietnam.
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Hepatitis B and C Co-Infections in Some HIV-Positive Populations in Cameroon, West Central Africa

As people infected with the human immunodeficiency virus (HIV) in Sub-Saharan Africa live longer due to availability of antiretroviral treatment (ART), so is the rise of associated infections with their burdens on patients. But reliable data on the prevalence of co-infection with hepatitis B (HBV) or C (HCV) still remains sparse and many individuals with HIV do not know their co-infection status.  

Of 531 participants, 68% were females and 32% males. Mean CD4 count was ~400 cells/μl. Seroprevalence rates for HBsAg and HCV-Ab were 23.7%, and 7.2%, respectively. Associations assessed using logistic regression revealed that HBsAg but not HCV-Ab positivity was linked to age, lower CD4 count and residing in an urban rather than in a rural setting. 

This high prevalence of co-infection with HBV raises the urgent need to systematically screen all newly diagnosed HIV cases for co-infection in Cameroon and other regions of sub-Saharan Africa where HIV accounts for the majority of the global infection, so as to improve management strategies for HBV infection and ART implementation.

Below:  Age-specific prevalence for co-infection with HBV or HCV. Prevalence rates were calculated based on the proportion of study participants at risk of co-infection in a given age group.

Below: Region-specific prevalence for co-infection with HBV or HCV. Prevalence rates were calculated based on the proportion of study participants at risk of co-infection in a given region

Read more at: http://goo.gl/6LJVE4

By: Jean Jacques N. Noubiap, Lucy A. Agyingi, Johnson N. Ngai

Serology Unit, Medical Diagnostic Center, Yaounde, Cameroon

Peter V. Aka

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America

Aubin J. Nanfack, Phillipe N. Nyambi

Department of Pathology, New York University School of Medicine, New York, New York, United States of America

Aubin J. Nanfack

Faculty of Medicine and Surgery, Department of Immunology and Applied Biotechnology, University of Rome Tor Vergatta, Rome, Italy

Lucy A. Agyingi

Faculty of Science, University of Dschang, Dschang, Cameroon

Phillipe N. Nyambi

Veterans Affairs New York Harbor Healthcare Systems, New York, New York, United States of America

High Incidence of Diagnosis with Syphilis Co-Infection among Men Who Have Sex with Men in An HIV Cohort in Ontario, Canada

Below:  Rate of new syphilis diagnoses among HIV-positive MSM, OHTN Cohort Study, 2006–2010. Re-diagnosis defined as a four-fold rise in RPR titre.

First syphilis diagnoses occurred at a rate of 2.0 per 100 person-years (95 % CI 1.7, 2.4; 121 cases) whereas the re-diagnosis rate was 7.5 per 100 person-years (95 % CI 6.3, 8.8; 136 cases). We observed higher rates over time and among men who were aged <30 years, receiving care in the two largest urban centers, or had a previous syphilis diagnosis. Syphilis diagnosis was less common among Indigenous men, men with higher CD4 cell counts, and, for first diagnoses only, among men with less than high school education.

Compared to reported cases in the general male population, incidence of a new syphilis diagnosis was over 300 times greater among HIV-positive MSM but year-to-year changes reflected provincial trends. Re-diagnosis was common, suggesting treatment failure or re-infection. Novel syphilis control efforts are needed among HIV-positive MSM.

Read more at:   http://ht.ly/R8CZS HT @UofT_dlsph

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 

Incidence of Tuberculosis and Immunological Profile of TB/HIV Co-Infected Patients in Nigeria

Below:  10 years CD4 count trend disaggregated by presence of TB infection

During the 10-year period, 47(13.62%) had TB [incidence was 7.43 per (1,000) person year)]. It is associated with decreasing age (OR = 0.98), female gender (OR = 0.83), being on first line ART other than AZT (OR = 0.87), poor adherence (OR = 1.25), change in ART regimen (OR = 2.3) and ART treatment failure (OR = 1.51). Odds of TB occurrence was also associated with CD4 increment at 10 years (OR = 0.99). Those with TB/HIV co-infection tend to have statistically significant shorter time to failing first line ART regimen compared to those with HIV infection alone.

There was high incidence of TB in the studied HIV cohort with a deleterious effect on the outcome of ART treatment. There is need for early TB screening and re-screening among all HIV patients.

Read more at:  http://ht.ly/QSjne HT @KFMC_RIYADH

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

Completeness and Reliability of the Republic of South Africa National Tuberculosis (TB) Surveillance System

Below:  Schematic of the design of the TB Surveillance System for recording and reporting TB information for the National TB Program, South Africa

Over one-third (33.7 %) of all persons with presumptive TB recorded as smear positive in the TB Suspect Register did not have any records documenting notification, treatment, or management for TB disease. Of 1339 persons with a record as a TB patient at the facility, 1077 (80 %) were recorded in all data sources. Over 98 % of records contained complete age and sex data. Completeness varied for HIV status (53-86 %; p < 0.001) and DOT during the intensive phase of treatment (17-54 %; p < 0.001). Agreement for sex was excellent across sources (kappa 0.94); moderate for patient type (0.78), treatment regimen (0.79), treatment outcome (0.71); and poor for HIV status (0.33).

The current evaluation revealed that one-third of persons diagnosed with TB disease may not have been notified of their disease or initiated on treatment (‘initial defaulters’). The ETR is not capturing all TB patients. Further, among patients with a TB record, completeness and reliability of information in the TB Surveillance System is inconsistent across data sources. Actions are urgently needed to ensure that all diagnosed patients are treated and managed and improve the integrity of surveillance information.

Read more at:   http://ht.ly/QLMN5 HT @CDCgov 

Hepatitis C in Human Immunodeficiency Virus Co-Infected Individuals: Is This Still a “Special Population”?

Below:  Comparison of week-12 sustained virological response rates between patients co-infected with hepatitis C virus and human immunodeficiency virus mono-infected patients treated with the same regimens containing direct acting antivirals in clinical trials (Data from similar studies were arithmetically pooled). 3D: Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir; BOC: Boceprevir; FDV: Faldaprevir; GT: HCV genotype; LDV: Ledipasvir; PegIFN: Pegylated Interferon; RBV: Ribavirin; SMV: Simeprevir; SOF: Sofosbuvir; TE: Treatment experienced; TN: Treatment naïve; TR: Prior relapse after treatment; TVR: Telaprevir; /: Indicates co-formulation; +/-: With or without.

A substantial proportion of individuals with chronic hepatitis C virus (HCV) are co-infected with human immunodeficiency virus (HIV). Co-infected individuals are traditionally considered as one of the “special populations” amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals (DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the “special population” designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users.

Read more at:   http://ht.ly/QIfEz HT @RoyalFreeNHS

Epidemiology of the Viral Hepatitis-HIV Syndemic in San Francisco: A Collaborative Surveillance Approach.

Public Health Rep. 2014 Jan;129(Suppl 1):95-101. More at:  http://ht.ly/skqUd

In San Francisco, hepatitis reporting is primarily through passive laboratory-based surveillance, and HIV/AIDS reporting is primarily through laboratory-initiated active surveillance. We conducted the registry linkage in 2010 using a sequential algorithm.

The registry match included 31,997 HBV-infected people who were reported starting in 1984; 10,121 HCV-infected people who were reported starting in 2001; and 34,551 HIV/AIDS cases reported beginning in 1981. Of the HBV and HCV cases, 6.3% and 12.6% were coinfected with HIV, respectively. The majority of cases were white males; however, black people were disproportionately affected. For more than 90% of the HBV/HIV cases, male-to-male sexual contact (men who have sex with men [MSM]) was the risk factor for HIV infection. Injection drug use was the most frequent risk factor for HIV infection among the HCV/HIV cases; however, 35.6% of the HCV/HIV coinfected males were MSM but not injection drug users.

By linking the two registries, we found new ways to foster collaborative work and expand our programmatic flexibility. This analysis identified particular populations at risk for coinfection, which can be used by viral hepatitis and HIV screening, prevention, and treatment programs to integrate, enhance, target, and prioritize prevention services and clinical care within the community to maximize health outcomes.  HT @SanFranciscoDPH

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