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Summary Background Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups. Methods We searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400. Findings Of 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49–0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43–1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per μL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR. Interpretation Isoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV. Funding National Institutes of Health and National Institute of Allergy and Infectious Diseases.

Background Early initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)infected patients who have tuberculosis reduces mortality among patients with low CD4 counts, but it increases the risk of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS). Methods We conducted this randomized, double-blind, placebo-controlled trial to assess whether prophylactic prednisone can safely reduce the incidence of paradoxical tuberculosis-associated IRIS in patients at high risk for the syndrome. We enrolled HIV-infected patients who were initiating ART (and had not previously received ART), had started tuberculosis treatment within 30 days before initiating ART, and had a CD4 count of 100 cells or fewer per microliter. Patients received either prednisone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or placebo. The primary end point was the development of tuberculosis-associated IRIS within 12 weeks after initiating ART, as adjudicated by an independent committee. Results Among the 240 patients who were enrolled, the median age was 36 (interquartile range, 30 to 42), 60% were men, and 73% had microbiologically confirmed tuberculosis; the median CD4 count was 49 cells per microliter (interquartile range, 24 to 86), and the median HIV type 1 RNA viral load was 5.5 log10 copies per milliliter (interquartile range, 5.2 to 5.9). A total of 120 patients were assigned to each group, and 18 patients were lost to follow-up or withdrew. Tuberculosis-associated IRIS was diagnosed in 39 patients (32.5%) in the prednisone group and in 56 (46.7%) in the placebo group (relative risk, 0.70; 95% confidence interval [CI], 0.51 to 0.96; P=0.03). Open-label glucocorticoids were prescribed to treat tuberculosis-associated IRIS in 16 patients (13.3%) in the prednisone group and in 34 (28.3%) in the placebo group (relative risk, 0.47; 95% CI, 0.27 to 0.81). There were five deaths in the prednisone group and four in the placebo group (P=1.00). Severe infections (acquired immunodeficiency syndromedefining illnesses or invasive bacterial infections) occurred in 11 patients in the prednisone group and in 18 patients in the placebo group (P=0.23). One case of Kaposis sarcoma occurred in the placebo group. Conclusions Prednisone treatment during the first 4 weeks after the initiation of ART for HIV infection resulted in a lower incidence of tuberculosis-associated IRIS than placebo, without evidence of an increased risk of severe infections or cancers. (Funded by the European and Developing Countries Clinical Trials Partnership and others; PredART ClinicalTrials.gov number, NCT01924286.)

PURPOSE OF REVIEW: Antiretroviral therapy (ART) is an essential, life-saving intervention for HIV infection. However, ART initiation is frequently complicated by the tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in TB endemic settings. Here, we summarize the current understanding highlighting the recent evidence. RECENT FINDINGS: The incidence of paradoxical TB-IRIS is estimated at 18% (95% CI 16-21%), higher than previously reported and may be over 50% in high-risk groups. Early ART initiation in TB patients increases TB-IRIS risk by greater than two-fold, but is critical in TB patients with CD4 counts less than 50 cells/μl because it improves survival. There remains no validated diagnostic test for TB-IRIS, and biomarkers recently proposed are not routinely used. Prednisone initiated alongside ART in selected patients with CD4 less than 100 cells/μl reduced the risk of paradoxical TB-IRIS by 30% in a recent randomized-controlled trial (RCT) and was not associated with significant adverse effects. Effective also for treating paradoxical TB-IRIS, corticosteroids remain the only therapeutic intervention for TB-IRIS supported by RCT trial data. TB-IRIS pathogenesis studies implicate high antigen burden, innate immune cell cytotoxicity, inflammasome activation and dysregulated matrix metalloproteinases in the development of the condition. SUMMARY: Specific biomarkers would aid in identifying high-risk patients for interventions and a diagnostic test is needed. Clinicians should consider prednisone for TB-IRIS prevention in selected patients. Future research should focus on improving diagnosis and investigating novel therapeutic interventions, especially for patients in whom corticosteroid therapy is contraindicated.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

Background Presence of isolated anti-HBc antibody is common in HIV-infected patients in endemic areas and could be caused by prior HBV infection with loss of anti-HBs antibody. The role of vaccination in these patients remains controversial and is based largely on limited and low quality data. We, therefore, conducted this study to determine immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody. Methods An open-label, randomized controlled trial was conducted among HIV-infected patients visiting HIV clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between July and September 2017. Inclusion criteria included ≥ 18 years of age, currently on a stable antiretroviral regimen, CD4+ cell count ≥ 200 cells/mm3, plasma HIV-1 RNA Results Of the 97 patients screened, 54 (32 male, mean age of 46 years) were enrolled and 27 were allocated to each of the vaccination groups. Anamnestic response occurred in 25.9% vs. 33.3% in 3-dose group vs. 4-dose group, respectively (p = 0.551). The vaccine response rates at week 28 were 85.2% in 3-dose group vs. 88.9% in 4-dose group (p = 1.000); geometric mean titer of anti-HBs antibody at week 28 was 63.8 and 209.8 mIU/mL in 3-dose group and 4-dose group, respectively (p = 0.030). No adverse events were reported. Conclusions An anamnestic response occurred in one-third of Thai HIV-infected patients with isolated anti-HBc antibody who received one dose of HBV vaccination; however, the majority were still unprotected. The use of either 3 or 4 standard-doses of vaccination was highly effective and should be recommended in all HIV-infected individuals with isolated anti-HBc antibody. Trial registration ClinicalTrials.gov; NCT03212911. Registered 11 July 2019, https://clinicaltrials.gov/ct2/show/NCT03212911

Background Detection of mycobacterial lipoarabinomannan antigen in urine has emerged as a potential point-of-care test for diagnosis of tuberculosis. This study aimed to evaluate the accuracy of the lateral flow urine lipoarabinomannan (LF-LAM) assay for diagnosis of active tuberculosis among Thai adults with advanced human immunodeficiency virus (HIV) infection. Methods HIV-infected adult patients with CD4 cell counts ≤200/μL and symptoms suggestive of active tuberculosis were prospectively recruited from both inpatient and outpatient settings at Siriraj Hospital and Chonburi Hospital in Thailand during the study period from December 2015 to March 2017. Freshly collected urine samples were applied to the Alere Determine TB LAM Ag test strip using a grade 1 cutoff, according to the manufacturer’s grading system. The diagnostic accuracy of the LF-LAM test was assessed against a microbiological reference standard (definite tuberculosis) or a composite reference standard (definite and probable tuberculosis). Results Of the 280 patients who were included, 72 (25.7%) had definite and 65 (23.2%) had probable tuberculosis. Among patients with definite tuberculosis, the LF-LAM test yielded a sensitivity of 75.0% and a specificity of 76.0%. It had the highest sensitivity (90.5%) in HIV-infected patients with CD4 cell counts

BACKGROUND: A vaccine to interrupt the transmission of tuberculosis is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS: We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS: M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).

OBJECTIVE: Both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) reduce tuberculosis risk in individuals living with HIV. We sought to estimate the broader, population-wide impact of providing a pragmatically-implemented 12-month IPT regimen to ART recipients in a high-burden community. DESIGN: Dynamic transmission model of a tuberculosis-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS: We projected the five-year impact of delivering a 12-month IPT regimen community-wide to 85% of new ART initiators and 15%/year of those already on ART, accounting for IPT-attributable reductions in TB infection, progression, and transmission. We also evaluated scenarios of continuously-delivered IPT, ongoing ART scale-up, and lower tuberculosis incidence. RESULTS: Under historical (early 2010 s) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 (95% credible interval [CrI] 11-29) people treated. It lowered tuberculosis incidence by a projected 23% (95%CrI 14-30%) among people receiving ART, and by 5.2% (95%CrI 2.9-8.7%) in the total population. Continuous IPT reduced the number needed to treat to prevent one case of tuberculosis to 10 (95%CrI 7-16), though it required 74% more person-years of therapy (95%CrI 64-94%) to prevent one TB case, relative to 12-month therapy. Under expanding ART coverage, the tuberculosis incidence reduction achieved by 12-month IPT grew to 7.6% (95%CrI 4.3-12.6%). Effect sizes were similar in a simulated setting of lower tuberculosis incidence. CONCLUSIONS: IPT in conjunction with ART reduces tuberculosis incidence among those who receive therapy and has additional impact on tuberculosis transmission in the population.

INTRODUCTION: Inflammation, or the prolonged resolution of inflammation, contributes to death from tuberculosis. Interest in inflammatory mechanisms and the prospect of beneficial immune modulation as an adjunct to antibacterial therapy has revived and the concept of host directed therapies has been advanced. Such renewed attention has however, overlooked the experience of such therapy with corticosteroids. AREAS COVERED: The authors conducted literature searches and evaluated randomized clinical trials, systematic reviews and current guidelines and summarize these findings. They found evidence of benefit in meningeal and pericardial tuberculosis in HIV-1 uninfected persons, but less so in those HIV-1 co-infected and evidence of harm in the form of opportunist malignancy in those not prescribed antiretroviral therapy. Adjunctive corticosteroids are however of benefit in the treatment and prevention of paradoxical HIV-tuberculosis immune reconstitution inflammatory syndrome. EXPERT COMMENTARY: Further high quality clinical trials and experimental medicine studies are warranted and analysis of materials arising from such studies could illuminate ways to improve corticosteroid efficacy or identify novel pathways for more specific intervention.

Background The World Health Organization (WHO) Consolidated antiretroviral therapy (ART) guidelines set the CD4+ T-cell count threshold to 500 cells/mm3 in 2013, and 2015 guidelines recommend treating all HIV-infected adults regardless of their CD4+ T-cell count. To inform the decision-making around ART guidelines for people living with HIV, we systematically reviewed the literature to estimate differences in clinical benefits between individuals starting treatment with baseline CD4+ T-cell counts ≥500 cells/mm3 (early initiation) as compared to

© 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society. Introduction: The concept of "therapeutic citizenship" has drawn attention to ways in which public testimony, the "story-telling in the public sphere" undertaken by people living with HIV (PLHIV), has shaped the global response to the epidemic. This paper presents qualitative findings from two large studies in eastern Africa that reveal how the advent of population-based HIV testing campaigns and efforts to accelerate antiretroviral "treatment for all" has precipitated a rapidly expanding therapeutic citizenship "project," or social movement. The title of this paper refers to Goffman's original conceptualization of stigma as a social process through which a person's identity is rendered "spoiled." Methods: Data were derived from qualitative studies embedded within two clinical trials, Sustainable East African Research in Community Health (SEARCH) (NCT# 01864603) in Kenya and Uganda, and START-ART (NCT# 01810289) in Uganda, which aimed to offer insights into the pathways through which outcomes across the HIV care continuum can be achieved by interventions deployed in the studies, any unanticipated consequences, and factors that influenced implementation. Qualitative in-depth semi-structured interviews were conducted among cohorts of adults in 2014 through 2015; across both studies and time periods, 217 interviews were conducted with 166 individuals. Theoretically informed, team-based analytic approaches were used for the analyses. Results: Narratives from PLHIV, who have not always been conceptualized as actors but rather usually as targets of HIV interventions, revealed strongly emergent themes related to these individuals' use of HIV biomedical resources and discourses to fashion a new, empowered subjecthood. Experiencing the benefits of antiretroviral therapy (ART) emboldens many individuals to transform their "spoiled" identities to attain new, valorized identities as "advocates for ART" in their communities. We propose that the personal revelation of what some refer to as the "gospel of ARVs," the telling of personal stories about HIV in the public sphere and actions to accompany other PLHIV on their journey into care, is driven by its power to redeem the "spoiled identity:" it permits PLHIV to overcome self-stigma and regain full personhood within their communities. Conclusions: PLHIV are playing an unanticipated but vital role in the successful implementation of HIV care cascade interventions.

Background Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively. Methods DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling. Time to virological failure, defined as the first viral load measurement ≥200 copies/mL after 48 weeks of ART, was analysed using Kaplan-Meier plots and Cox regression models. Results Overall, 65% of DART trial patients were female. Patients initiated first-line ART at a median (interquartile range; IQR) age of 37 (32–42) and with a median CD4 cell count of 86 (32–140). After 240 weeks of ART, patients initiating dual-class nucleoside reverse-transcriptase inhibitor (NRTI) -non-nucleoside reverse-transcriptase (NNRTI) regimens containing nevirapine + zidovudine + lamivudine had a lower incidence of virological failure than patients on triple-NRTI regimens containing tenofovir + zidovudine + lamivudine (21% vs 40%; hazard ratio (HR) =0.48, 95% CI:0.38–0.62; p

Contains fulltext : 177008.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To assess the efficacy and safety of a new single-tablet regimen (STR) of tenofovir disoproxil fumarate (TDF) 300mg, lamivudine (3TC) 300mg, and efavirenz (EFV) 600mg in HIV-infected Thai patients. METHODS: This was a prospective study performed for 144 weeks among 51 treatment-naive patients and 49 experienced patients on separate tablets of TDF, 3TC, and EFV with HIV RNA

For eradication of tuberculosis (TB) by 2050, the declared aim of the Stop TB Partnership, novel treatment strategies are indispensable. The emerging epidemic of multi-drug resistant (MDR) TB has fuelled the debate about TB vaccines, as increasing numbers of patients can no longer be cured by pharmacotherapy. Of several proposed modalities, TB vaccines administered in therapeutic manner represents a promising alternative, despite the controversial history due to the occurrence of exacerbated immune response. A modified concept of immunotherapy is required in order to justify further exploration. In this paper we systematically reviewed the most advanced therapeutic vaccines for TB. We address the rationale of immunotherapeutic vaccination combined with optimized pharmacotherapy in active TB. We summarize preclinical and patient data regarding the five most advanced therapeutic vaccines currently in the pipeline. Of the five products that have been tested in animal models and in humans during active or latent TB, the quality of the published clinical reports of two of these products justify further studies in patients with active TB. This systematic review fuels further clinical evaluation eventually including head-to-head comparative studies. (C) 2014 Elsevier Ltd.

For eradication of tuberculosis (TB) by 2050, the declared aim of the Stop TB Partnership, novel treatment strategies are indispensable. The emerging epidemic of multi-drug resistant (MDR) TB has fuelled the debate about TB vaccines, as increasing numbers of patients can no longer be cured by pharmacotherapy. Of several proposed modalities, TB vaccines administered in therapeutic manner represents a promising alternative, despite the controversial history due to the occurrence of exacerbated immune response. A modified concept of immunotherapy is required in order to justify further exploration. In this paper we systematically reviewed the most advanced therapeutic vaccines for TB. We address the rationale of immunotherapeutic vaccination combined with optimized pharmacotherapy in active TB. We summarize preclinical and patient data regarding the five most advanced therapeutic vaccines currently in the pipeline. Of the five products that have been tested in animal models and in humans during active or latent TB, the quality of the published clinical reports of two of these products justify further studies in patients with active TB. This systematic review fuels further clinical evaluation eventually including head-to-head comparative studies. (C) 2014 Elsevier Ltd.

Objective: The objective of this study was to identify determinants for tuberculosis (TB) among HIV-infected adults in Northwest Ethiopia. Design: Case–control study. Setting: Three hospitals and 10 health centres in Northwest Ethiopia. Participants: A total of 446 individuals consented to participate in the study (150 cases and 296 controls). Cases were HIV-infected adults diagnosed with active TB, and controls were HIV-infected adults without active TB. Main outcome measure: The link between TB and determinants was assessed using logistic regression. Determinants were categorised as sociodemographic, host-related, clinical and environmental. Results: Smoking (adjusted OR (AOR) 5.47; 95% CI 2.26 to 13.22), presence of a TB patient in the family (AOR 2.66; 95% CI 1.25 to 5.66), alcohol consumption (AOR 2.49; 95% CI 1.29 to 4.80) and chewing khat (AOR 2.22; 95% CI 1.11 to 4.41) were independent determinants for increased occurrence of TB. Highly active antiretroviral therapy (HAART) (AOR 0.25; 95% CI 0.13 to 0.51), isoniazid preventive therapy (IPT) (AOR 0.22; 95% CI 0.11 to 0.41) and cotrimoxazole preventive therapy (AOR 0.32; 95% CI 0.19 to 0.55) had a protective effect against TB. Conclusions: HIV-infected adults with substance abuse (tobacco smoking, khat chewing and alcohol) should be prioritised for TB screening. This study reaffirmed that HAART and IPT are some of the best strategies for reducing TB occurrence in HIV-infected adults. These findings provide impetus to intensify tracing of TB household contacts. Published version

Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination.

Rationale: Isoniazid preventive therapy is effective in reducing the risk of tuberculosis (TB) in persons living with HIV (PLWH); however, screening must exclude TB disease before initiating therapy. Symptom screening alone may be insufficient to exclude TB disease in PLWH because some PLWH with TB disease have no symptoms. The addition of chest radiography (CXR) may improve disease detection.Objectives: The objective of the present analysis was to compare the costs and effects of the addition of CXR to the symptom screening process against the costs and effects of symptom screening alone.Methods: Using data from Botswana, a decision analytic model was used to compare a "Symptomonly'' policy against a "Symptom+CXR'' policy. The outcomes of interest were cost, death, and isoniazid-and multidrug-resistant TB in a hypothetical cohort of 10,000 PLWH. Measurements and MainResults: The Symptom+CXR policy prevented 16 isoniazid-and 0.3 multidrug-resistant TB cases; however, because of attrition from the screening process, there were 98 excess cases of TB, 15 excess deaths, and an additional cost of U. S. $127,100. The Symptom+CXR policy reduced deaths only if attrition was close to zero; however, to eliminate attrition the cost would be U. S. $2.8 million per death averted. These findings did not change in best-and worst-case scenario analyses.Conclusions: In Botswana, a policy with symptom screening only preceding isoniazid-preventive therapy initiation prevents more TB and TB-related deaths, and uses fewer resources, than a policy that uses both CXR and symptom screening.

The levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of nonfunctional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a two-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera were determined. Significant increases were found in the OPK titers and IgG levels for both serotypes after CV vaccination irrespective of HIV status. Increases in IgG levels and OPK titers were largely dependent on the CD4+ cell counts, except for increases in the IgG levels for serotype 4. The proportions with serum OPK titer equal to or greater than 8 were 0-4.3% for serotype 4 and 26.7-42.9% for serotype 14 before vaccination, but the proportions increased up to 43.3-86.2% for serotype 4 and 63.3-96.6% for serotype 14 in all three groups 2 months after CV vaccination. The serum OPK titers remained at levels higher than the pre-vaccination level for at least 8 months after CV vaccination. A single dose of CV could afford some protective immunity in HIV-infected African adults before the introduction of antiretroviral therapy., Vaccine, 26(38), pp.4962-4968; 2008

Tuberculosis is the leading cause of death among adults infected with human immunodeficiency virus (HIV), and rates of tuberculosis remain high even after preventive therapy. Among 908 HIV-infected adults in a trial of preventive treatment, we found self-reported alcohol consumption, low baseline CD4 count, high baseline viral load, and tuberculin skin test size >15 mm as independent risk factors for incident tuberculosis.

Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily didanosine (regimen A) or simplified once-daily dosed antiretroviral regimens consisting of nevirapine, didanosine, and lamivudine (regimen B) or saquinavir, ritonavir, didanosine, and lamivudine (regimen C). Results: At 48 weeks of therapy, the proportion of patients with a blood plasma HIV-1 RNA concentration (pVL)

Contains fulltext : 47519.pdf (Publisher’s version ) (Closed access) BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily didanosine (regimen A) or simplified once-daily dosed antiretroviral regimens consisting of nevirapine, didanosine, and lamivudine (regimen B) or saquinavir, ritonavir, didanosine, and lamivudine (regimen C). RESULTS: At 48 weeks of therapy, the proportion of patients with a blood plasma HIV-1 RNA concentration (pVL)

Background To evaluate the on-going scale-up of HIV programs, we assessed trends in patient characteristics at enrolment and ART initiation over 7 years of implementation. Methods Data were from Optimal Models, a prospective open cohort study of HIV-infected (HIV+) adults (≥15 years) and children (

Background The economic effects of poor immunologic recovery among HIV-infected patients receiving antiretroviral therapy (ART) in subSaharan Africa are not well understood. We examined the relationship between the CD4 counts of patients on long-term ART and employment outcomes in HIV-affected households in Lusaka, Zambia.Methods Administrative data and a household survey captured information on the clinical records, demographics and employment outcomes of the ART-treated adults and their adult family members (n = 311). Multivariable regression analyses were used to assess relationships between CD4 counts of ART-treated adults and household employment outcomes.Results Patients with a CD4 count of at least 350 cells/mu l were 22 percentage points more likely to be engaged in the labor force(P= 500 compared with = 350 versus

Objectives Control of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults. Design This was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naïve subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon γ (IFN-γ) ELISpot assays and flow-cytometric analysis. Results MVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-γ response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable. Conclusion MVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited., Article summary Article focus HIV infection increases susceptibility to TB, and globally, TB is the cause of death in up to half of AIDS deaths. There is an urgent need for a safe and effective TB vaccine in HIV-infected people. Key messages MVA85A, a leading candidate TB vaccine, is safe and well tolerated in HIV-infected people and does not induce changes in either CD4 count or HIV RNA load. MVA85A is immunogenic in HIV-infected people, and induces a similar immune profile to that seen in HIV-uninfected people, but the immunogenicity is less durable in HIV-infected people. Strengths and limitations of this study This is a Phase I study with 20 subjects, and further studies are needed in TB endemic countries in this important target population.