Hepatitis B,Hepatitis C and HIV-1 Coinfection in Two Informal Urban Settlements in Nairobi,Kenya

Background

HIV-1 and Hepatitis B and C viruses coinfection is common in Sub-Saharan Africa due to similar routes of transmission and high levels of poverty. Most studies on HIV-1 and Hepatitis B and C viruses have occurred in hospital settings and blood transfusion units. Data on Hepatitis B and C viruses and HIV-1 coinfection in informal urban settlements in Kenya are scanty, yet they could partly explain the disproportionately high morbidity and mortality associated with HIV-1 infections in these slums.

Objectives

The objective of this study was to determine the prevalence of HIV and Hepatitis B and C dual infection in urban slums in Nairobi.

Methods

Blood samples were collected from residents of Viwandani and Korogocho between 2006 and 2007. A structured questionnaire was used to obtain socio-demographic data from participants. Samples were screened for Hepatitis B surface antigen (HBsAg), anti-HCV and anti-HIV-1. Statistical analysis was done using STATA.

Results

Samples were successfully collected from 418 (32%) men and 890 (68%) females. The HIV-1, HBV and HCV prevalence was 20.4%, 13.3% and 0.76% respectively at the time of the study. Of the 268 (20.4%) HIV-1 positive participants, 56 (4.26%) had HBV while 6 (0.46%) had HCV. Of the 1041 HIV-1 negative participants, 117 (8.9%) had HBV while 4 (0.31%) had HCV. Only two people (0.15%) were co-infected with all the three viruses together.

Discussion

The odds of getting hepatitis infection were higher in HIV-1 participants (for HBV OR 2.08,p<0.005 and for HCV OR 5.93, p<0.005). HIV prevalence rates were similar in both informal settlements. HIV infection was highest in age group 35-39 years and among the divorced/separated or widowed. Prevalence of all viruses was highest in those who did not have any formal education.

Conclusion

The HIV prevalence in these informal settlements suggests a higher rate than what is observed nationally. The prevalence rates of HBV are significantly higher in the HIV-1 positive and negative populations. HCV as well as triple HIV-1, HBV and HCV coinfection are uncommon in Korogocho and Viwandani. This clearly indicates the need for HIV-1 control programmes and hepatitis B virus vaccination to be promoted through public awareness as preventive strategy.     

Opt-Out Panel Testing for HIV,Hepatitis B and Hepatitis C in an Urban Emergency Department: A Pilot Study

Objectives

Studies suggest 2 per 1000 people in Dublin are living with HIV, the level above which universal screening is advised. We aimed to assess the feasibility and acceptability of a universal opt-out HIV, Hepatitis B and Hepatitis C testing programme for Emergency Department patients and to describe the incidence and prevalence of blood-borne viruses in this population.

Methods

An opt-out ED blood borne virus screening programme was piloted from March 2014 to January 2015. Patients undergoing blood sampling during routine clinical care were offered HIV 1&2 antibody/antigen assay, HBV surface antigen and HCV antibody tests. Linkage to care where necessary was co-ordinated by the study team. New diagnosis and prevalence rates were defined as the new cases per 1000 tested and number of positive tests per 1000 tested respectively.

Results

Over 45 weeks of testing, of 10,000 patient visits, 8,839 individual patient samples were available for analysis following removal of duplicates. A sustained target uptake of >50% was obtained after week 3. 97(1.09%), 44(0.49%) and 447(5.05%) HIV, Hepatitis B and Hepatitis C tests were positive respectively. Of these, 7(0.08%), 20(0.22%) and 58(0.66%) were new diagnoses of HIV, Hepatitis B and Hepatitis C respectively. The new diagnosis rate for HIV, Hepatitis B and Hepatitis C was 0.8, 2.26 and 6.5 per 1000 and study prevalence for HIV, Hepatitis B and Hepatitis C was 11.0, 5.0 and 50.5 per 1000 respectively.

Conclusions

Opt-out blood borne viral screening was feasible and acceptable in an inner-city ED. Blood borne viral infections were prevalent in this population and newly diagnosed cases were diagnosed and linked to care. These results suggest widespread blood borne viral testing in differing clinical locations with differing population demographic risks may be warranted.     

High Prevalence and High Incidence of Coinfection with Hepatitis B,Hepatitis C,and Syphilis and Low Rate of Effective Vaccination against Hepatitis B in HIV-Positive Men Who Have Sex with Men with Known Date of HIV Seroconversion in Germany

Objectives

Men who have sex with men (MSM) are at higher risk for coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis than the general population. HIV infection and these coinfections accelerate disease progression reciprocally. This study evaluated the prevalence and incidence of these coinfections in HIV1-positive MSM in Germany.

Materials and Methods

As part of a nationwide, multicenter, prospective cohort study of HIV-infected MSM, plasma samples collected yearly were screened for HBsAg and antibodies to HBc, HBs, HCV, and syphilis. Samples with indications of active HBV or HCV infection were confirmed by polymerase chain reaction. Prevalence and incidence of each infection and incidence rates per study participant were calculated, and incidences over 4-year time intervals compared.

Results

This study screened 5,445 samples from 1,843 MSM. Median age at HIV seroconversion was 33 years. Prevalences of active, cleared, and occult HBV, and of active/cleared HCV were 1.7%, 27.1%, 0.2%, and 8.2%, respectively, and 47.5% had been effectively vaccinated against HBV. Prevalence of antibodies to Treponema pallidum and of triple or quadruple sexually transmitted infections (STIs) were 39.6% and 18.9%, respectively. Prevalence of STI, cleared HBV, HBV vaccination, and history of syphilis differed significantly among age groups. Incidences of HBV, HCV, and syphilis were 2.51, 1.54, and 4.06 per 100 person-years, respectively. Incidences of HCV and syphilis increased over time. HCV incidence was significantly higher in MSM coinfected with syphilis and living in Berlin, and syphilis incidence was significantly higher for MSM living in Berlin.

Discussion

Despite extensive HBV vaccination campaigns, fewer than 50% of screened MSM were effectively vaccinated, with a high proportion of HIV-positive MSM coinfected with HBV. High rates of STI coinfections in HIV-positive MSM and increasing incidences emphasize the need for better tailored campaigns for HBV vaccination and STI prevention.     

Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa

Background

Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART.

Methodology

Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis.

Findings

Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period.

Conclusion

Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.     

Tuberculosis Case Fatality and Other Causes of Death among Multidrug-Resistant Tuberculosis Patients in a High HIV Prevalence Setting, 2000-2008, South Africa

Introduction

South Africa has the highest reported rates of multi-drug resistant TB in Africa, typified by poor treatment outcomes, attributable mainly to high default and death rates. Concomitant HIV has become the strongest predictor of death among MDR-TB patients, while anti-retroviral therapy (ART) has dramatically reduced mortality. TB Case fatality rate (CFR) is an indicator that specifically reports on deaths due to TB.

Aim

The aim of this paper was to investigate causes of death amongst MDR-TB patients, the contribution of conditions other than TB to deaths, and to determine if causes differ between HIV-uninfected patients, HIV-infected patients receiving ART and those without ART.

Methods

We carried out a retrospective review of data captured from the register of the MDR-TB programme of the North West Province, South Africa. We included 671 patients treated between 2000–2008; 59% of the cohort was HIV-infected and 33% had received ART during MDR treatment. The register contained data on treatment outcomes and causes of death.

Results

Treatment outcomes between HIV-uninfected cases, HIV-infected cases receiving ART and HIV-infected without ART differed significantly (p<0.000). The cohort death rate was 24%, 13% for HIV-uninfected cases and 31% for HIV-infected cases. TB caused most of the deaths, resulting in a cohort CFR of 15%, 9% for HIV-uninfected cases and 20% for HIV-infected cases. Cohort mortality rate due to other conditions was 2%. AIDS-conditions rather than TB caused significantly more deaths among HIV-infected cases receiving ART than those not (p = 0.02).

Conclusions

The deaths among HIV-infected individuals contribute substantially to the high death rate. ART co-therapy protected HIV-infected cases from death due to TB and AIDS-conditions. Mechanisms need to be in place to ensure that HIV-infected individuals are retained in care upon completion of their MDR-TB treatment.     

Incidence of TB and HIV in Prospectively Followed Household Contacts of TB Index Patients in South Africa

Objective

To report the incidence rates of TB and HIV in household contacts of index patients diagnosed with TB.

Design

A prospective cohort study in the Matlosana sub-district of North West Province, South Africa.

Methods

Contacts of index TB patients received TB and HIV testing after counseling at their first household visit and were then followed up a year later, in 2010. TB or HIV diagnoses that occurred during the period were determined.

Results

For 2,377 household contacts, the overall observed TB incidence rate was 1.3 per 100 person years (95% CI 0.9–1.9/100py) and TB incidence for individuals who were HIV-infected and HIV seronegative at baseline was 5.4/100py (95% CI 2.9–9.0/100py) and 0.7/100py (95% CI 0.3–1.4/100py), respectively. The overall HIV incidence rate was 2.2/100py (95% CI 1.3–8.4/100py).

Conclusions

In the year following a household case finding visit when household contacts were tested for TB and HIV, the incidence rate of both active TB and HIV infection was found to be extremely high. Clearly, implementing proven strategies to prevent HIV acquisition and preventing TB transmission and progression to disease remains a priority in settings such as South Africa.     

Incidence of HIV and the Prevalence of HIV,Hepatitis B and Syphilis among Youths in Maputo,Mozambique: A Cohort Study

Background

Prevalence of HIV in Mozambique among individuals aged 15–49 years is 11.5%. The HIV prevalence is higher in women than in men across the country, peaking at ages 25–29 years and 35–39 years, respectively. In this study, we aimed at determining the prevalence and incidence of HIV, prevalence of Hepatitis B (HBV), and prevalence of syphilis in youths. We also characterized a cohort of youths for future participation in phase I/II HIV vaccine trials.

Methods

The study was conducted at a youth clinic in Maputo Central Hospital from August 2009 to October 2011. Youths of both genders aged 18–24 years (n = 1380) were screened for HIV using a sequential algorithm of two immunochromatographic assays, HBV using an enzyme linked immunosorbant test, and syphilis using a treponemal immunochromatographic strip test. The HIV seronegative participants (n = 1309) were followed-up for 12 months with quarterly study visits. The clinical and behavioral data were collected using structured questionnaires. The HIV seroconversions were confirmed by a molecular assay.

Results

The study population was female dominant (76.8%). All participants had a formal education, with 44.6% studying for technical or higher education degrees. The mean age at sexual debut was 16.6 years (SD: ±1.74), with 85.6% reporting more than one sexual partner in life. The screening showed the prevalence of HIV, HBV, and syphilis at 5.1% (95% CI: 3.97–6.31), 12.2% (95% CI 10.5%–14.0%), and 0.36% (95% CI 0.15%–0.84%), respectively. The HIV incidence rate was found to be 1.14/100 person years (95% CI: 0.67–1.92). Retention rates were stable throughout the study being 85.1% at the last visit.

Conclusion

Incidence of HIV in this cohort of youths in Maputo was relatively low. Also, the prevalence of HIV and syphilis was lower than the national values in this age group. However, the HBV prevalence was higher than in previous reports in the country.     

Hepatitis C Virus Co-Infection Increases the Risk of Anti-Tuberculosis Drug-Induced Hepatotoxicity among Patients with Pulmonary Tuberculosis

Background

The country of Georgia has a high prevalence of tuberculosis (TB) and hepatitis C virus (HCV) infection.

Purpose

To determine whether HCV co-infection increases the risk of incident drug-induced hepatitis among patients on first-line anti-TB drug therapy.

Methods

Prospective cohort study; HCV serology was obtained on all study subjects at the time of TB diagnosis; hepatic enzyme tests (serum alanine aminotransferase [ALT] activity) were obtained at baseline and monthly during treatment.

Results

Among 326 study patients with culture-confirmed TB, 68 (21%) were HCV co-infected, 14 (4.3%) had chronic hepatitis B virus (HBV) infection (hepatitis B virus surface antigen positive [HBsAg+]), and 6 (1.8%) were HIV co-infected. Overall, 19% of TB patients developed mild to moderate incident hepatotoxicity. In multi-variable analysis, HCV co-infection (adjusted Hazards Ratio [aHR]=3.2, 95% CI=1.6-6.5) was found to be an independent risk factor for incident anti-TB drug-induced hepatotoxicity. Survival analysis showed that HCV co-infected patients developed hepatitis more quickly compared to HCV seronegative patients with TB.

Conclusion

A high prevalence of HCV co-infection was found among patients with TB in Georgia. Drug-induced hepatotoxicity was significantly associated with HCV co-infection but severe drug-induced hepatotoxicity (WHO grade III or IV) was rare.     

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival

Background

We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

Methods

Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

Results

A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

Conclusion

In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.     

Linkage to HIV,TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town,South Africa

Background

HIV counseling and testing may serve as an entry point for non-communicable disease screening.

Objectives

To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit.

Methods

A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined.

Results

Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic.

Conclusion

Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care.     

The Hepatitis C Cascade of Care: Identifying Priorities to Improve Clinical Outcomes

Background

As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them.

Methods

We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation.

Main measures

Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs).

Results

We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals.

Conclusions

We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points.     

Efficient Identification of HIV Serodiscordant Couples by Existing HIV Testing Programs in South Brazil

Objective

To examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil.

Methods

We surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population.

Results

Among 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5).

Conclusion

It is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission.     

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

Background

Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa.

Methods

Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts.

Results

Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART.

Conclusion

In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed.     

Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials

Background

Infection with Human Immunodeficiency virus (HIV) is an important risk factor for Tuberculosis (TB). Anti-Retroviral Therapy (ART) has improved the prognosis of HIV and reduced the risk of TB infected patients. Isoniazid Preventive Therapy (IPT) aims to reduce the development of active TB in patients with latent TB.

Objective

Systematically review and synthesize effect estimates of IPT for TB prevention in adult HIV patients. Secondary objectives were to assess the effect of IPT on HIV disease progression, all-cause mortality and adverse drug reaction (ADR).

Search Strategy

Electronic databases were searched to identify relevant articles in English available by September 11^th 2015.

Selection Criteria

Research articles comparing IPT to placebo or no treatment in HIV infected adults using randomized clinical trials.

Data Analysis

A qualitative review included study-level information on randomization and treatment allocation. Effect estimates were pooled using random-effects models to account for between-study heterogeneity.

Main Results

This review assessed ten randomized clinical trials that assigned 7619 HIV patients to IPT or placebo. An overall 35% of TB risk reduction (RR = 0.65, 95% CI (0.51, 0.84)) was found in all participants, however, larger benefit of IPT was observed in Tuberculin Skin Test (TST) positive participants, with pooled relative risk reduction of 52% [RR = 0.48; 95% CI (0.29, 0.82)] and with a prediction interval ranging from 0.13 to 1.81. There was no statistically significant effect of IPT on TB occurrence in TST negative or unknown participants. IPT also reduced the risk of HIV disease progression in all participants (RR = 0.69; 95% CI (0.48, 0.99)) despite no benefits observed in TST strata. All-cause mortality was not affected by IPT although participants who had 12 months of IPT tend to have a reduced risk (RR = 0.65; 95% CI(0.47, 0.90)). IPT had an elevated, yet statistically non-significant, risk of adverse drug reaction [RR = 1.20; 95% CI (1.20, 1.71)]. Only a single study assessed the effect of IPT in combination with ART in preventing TB and occurrence of multi-drug resistant tuberculosis.

Conclusions

IPT use substantially contributes in preventing TB in persons with HIV in general and in TST positive individuals in particular. More evidence is needed to explain discrepancies in the protective effect of IPT in these individuals.     

Time to Death and Associated Factors among Tuberculosis Patients in Dangila Woreda,Northwest Ethiopia

Background

Tuberculosis (TB) is among the leading causes of morbidity and mortality worldwide. More than 70% of the deaths of TB patients occur during the first two months of TB treatment. The major risk factors that increase early death of TB patients are being positive for human immunodeficiency virus (HIV), being of old age, being underweight or undergoing re-treatment.

Objective

To assess the time of reported deaths and associated factors in a cohort of patients with TB during TB treatment.

Methods

An institution-based retrospective cohort study was analyzed in Dangila Woreda, Northwest Ethiopia from March 1^st through March 30, 2014. All TB patients registered in the direct observed treatment (DOTs) clinic from 2008–2012 were included in the study. Data were entered into EpiData and exported to SPSS for analysis. The survival probability was analyzed by the Kaplan Meier method and Cox regression analysis was applied to investigate factors associated with death during TB treatment.

Results

From a total of 872 cases registered in TB registry log book, 810 were used for the analysis of which 60 (7.4%) died during the treatment. The overall mortality rate was 12.8/1000 person months of observation. A majority of TB deaths 34 (56.7%) occurred during the intensive phase of the treatment, and the median time of death was at two months of the treatment. Age, HIV status and baseline body weight were independent predictors of death during TB treatment.

Conclusions

Most deaths occurred in the first two months of TB treatment. Old age, TB/HIV co-infection and a baseline body weight of <35 kg increased the mortality during TB treatment. Therefore, a special follow up of TB patients during the intensive phase, of older patients and of TB/HIV co-infected cases, as well as nutritionally supplementing for underweight patients may be important to consider as interventions to reduce deaths during TB treatment.     

A Century of Tuberculosis Epidemiology in the Northern and Southern Hemisphere: The Differential Impact of Control Interventions

Background

Cape Town has one of the highest TB burdens of any city in the world. In 1900 the City of Cape Town, New York City and London had high mortality of tuberculosis (TB). Throughout the 20th century contemporaneous public health measures including screening, diagnosis and treatment were implemented in all three settings. Mandatory notification of TB and vital status enabled comparison of disease burden trajectories.

Methods

TB mortality, notification and case fatality rates were calculated from 1912 to 2012 using annual TB notifications, TB death certifications and population estimates. Notification rates were stratified by age and in Cape Town by HIV status (from 2009 onwards).

Results

Pre-chemotherapy, TB mortality and notification rates declined steadily in New York and London but remained high in Cape Town. Following introduction of combination chemotherapy, mean annual case fatality dropped from 45–60% to below 10% in all three settings. Mortality and notification rates subsequently declined, although Cape Town notifications did not decline as far as those in New York or London and returned to pre-chemotherapy levels by 1980. The proportional contribution of childhood TB diminished in New York and London but remained high in Cape Town. The advent of the Cape Town HIV-epidemic in the 1990s was associated with a further two-fold increase in incidence. In 2012, notification rates among HIV-negatives remained at pre-chemotherapy levels.

Conclusions

TB control was achieved in New York and London but failed in Cape Town. The TB disease burden trajectories started diverging before the availability of combination chemotherapy in 1952 and further diverged following the HIV epidemic in 1990. Chemotherapy impacted case fatality but not transmission, evidenced by on-going high childhood TB rates. Currently endemic TB results from high on-going transmission, which has been exacerbated by the HIV epidemic. TB control will require reducing transmission, which is inexorably linked to prevailing socio-economic factors.     

Diabetes Is Associated with Worse Clinical Presentation in Tuberculosis Patients from Brazil: A Retrospective Cohort Study

Background

The rising prevalence of diabetes mellitus (DM) worldwide, especially in developing countries, and the persistence of tuberculosis (TB) as a major public health issue in these same regions, emphasize the importance of investigating this association. Here, we compared the clinical profile and disease outcomes of TB patients with or without coincident DM in a TB reference center in Brazil.

Methods

We performed a retrospective analysis of a TB patient cohort (treatment naïve) of 408 individuals recruited at a TB primary care center in Brazil between 2004 and 2010. Data on diagnosis of TB and DM were used to define the groups. The study groups were compared with regard to TB disease presentation at diagnosis as well as to clinical outcomes such as cure and mortality rates upon anti-tuberculosis therapy (ATT) initiation. A composite score utilizing clinical, radiological and microbiological parameters was used to compare TB severity between the groups.

Results

DM patients were older than non-diabetic TB patients. In addition, diabetic individuals more frequently presented with cough, night sweats, hemoptysis and malaise than those without DM. The overall pattern of lung lesions assessed by chest radiographic examination was similar between the groups. Compared to non-diabetic patients, those with TB-diabetes exhibited positive acid-fast bacilli in sputum samples more frequently at diagnosis and at 30 days after ATT initiation. Notably, higher values of the TB severity score were significantly associated with TB-diabetes comorbidity after adjustment for confounding factors. Moreover, during ATT, diabetic patients required more frequent transfers to TB reference hospitals for complex clinical management. Nevertheless, overall mortality and cure rates were indistinguishable between the study groups.

Conclusions

These findings reinforce the idea that diabetes negatively impacts pulmonary TB severity. Our study argues for the systematic screening for DM in TB reference centers in endemic areas.     

Immune Activation Response in Chronic HIV-Infected Patients: Influence of Hepatitis C Virus Coinfection

Objectives

We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection) which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated.

Patients and methods

Seventy HIV-infected patients [monoinfected by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver cirrhosis)] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months).

Results

Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase.

Conclusion

In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients.     

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Objective

To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART).

Design

Retrospective analysis of a prospective cohort study.

Setting

Italian HIV care centers participating to the ICONA Foundation cohort.

Participants

Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up.

Methods

Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD.

Results

Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45–3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4>3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4>3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART.

Conclusions

The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.     

Predictors and Timing of ATT Initiation among HIV-TB Patients at ART Centers of Karnataka,India: Two Year Follow-Up

Background

In India, TB and HIV co-infection remains as a serious public health problem. From 2006 onwards, the intensified TB-HIV collaborative activities are being jointly implemented by National AIDS Control Programme (NACP) and Revised National TB Control programme (RNTCP) at high HIV burden states.

Objectives

To determine (a) the predictors of outcome among a cohort of HIV-TB co-infected patients after two years after initiation of ART treatment. (b) prognostic significance of time difference between the initiation of ATT and ART in HIV-TB co-infected patients.

Methods

Patients registered at sixteen ART centres in Karnataka, from October through December 2009 formed the study cohort and were followed till December 2011.

Results

A total of 604 HIV-TB patients were registered. Follow-up (a) at the end of one year had shown 63.6% (377)patients with unfavorable TB treatment outcomes (b) at the end of second year, 55.6% (336)patients were alive on ART treatment. The variables male, smear negative TB, CD4 count less than 50cells per cumm and unfavorable TB outcome were significantly associated with unfavorable ART treatment outcome.

Conclusions

The programmes need to review the existing strategies and strengthen HIV-TB collaborative activities for timely treatment initiation with intensive monitoring of HIV-TB patients on treatment.