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      HIV‐associated morbidity and mortality in a setting of high ART coverage: prospective surveillance results from a district hospital in Botswana

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          Abstract

          Introduction

          Antiretroviral therapy (ART) has significantly improved survival in Africa in recent years. In Botswana, where adult HIV prevalence is 21.9%, AIDS‐related mortality is estimated to have declined by 58% between 2005 and 2013 following the initial wide‐spread introduction of ART, and ART coverage has steadily increased reaching 84% in 2016. However, there remains little data about the burden of HIV and its impact on mortality in the hospital setting where most deaths occur. We aimed to describe the burden of HIV and related morbidity and mortality among hospitalized medical patients in a district hospital in southern Botswana in the era of widespread ART coverage.

          Methods

          We prospectively reviewed medical admissions to Scottish Livingstone Hospital from December 2015 to November 2017 and recorded HIV status, demographics, clinical characteristics and final diagnoses at discharge, death or transfer. We ascertained outcomes and determined factors associated with mortality. Results were compared with similar surveillance data collected at the same facility in 2011 to 2012.

          Results

          A total of 2316 admissions occurred involving 1969 patients; 42.4% were of HIV‐positive patients, 46.9% of HIV‐negative patients and 10.7% of patients with unknown HIV status. Compared to HIV‐negative patients, HIV‐positive patients had younger age (mean 42 vs. 64 years, p < 0.0001) and higher mortality (22.2% vs. 18.0%, p = 0.03). Tuberculosis was the leading diagnosis among mortality cases in both groups but accounted for a higher proportion of deaths among HIV‐positive admissions (44.5%) compared with HIV‐negative admissions (19.4%, p < 0.0001). Compared with similar surveillance in 2011 to 2012, HIV prevalence was lower (42.4% vs. 47.6%, p < 0.01), and among HIV‐positive admissions: ART coverage was higher (72.2% vs. 56.2%, p < 0.0001), viral load suppression was similar (78.6% vs. 80.3%, p = 0.77), CD4 counts were higher (55.0% vs. 44.6% with CD4 ≥200 cells/mm 3, p < 0.001), mortality was similar (22.2 vs. 22.7%, p = 0.93), tuberculosis diagnoses increased (27.5% vs. 20.1%, p < 0.01) and tuberculosis‐associated mortality was higher (35.9% vs. 24.7%, p = 0.05).

          Conclusions

          Despite high ART‐coverage in Botswana, HIV‐positive patients continue to be disproportionately represented among hospital admissions and deaths. Deaths from tuberculosis may be contributing to lack of reduction in inpatient mortality. Our findings suggest that control of HIV and tuberculosis remain top priorities for reducing inpatient mortality in Botswana.

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          Most cited references12

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          AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study.

          To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era. A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S. HIV clinics. We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994-2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period. Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/microl) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994-1997, 1998-2002, and 2003-2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003-2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% opportunistic illness events occurred at CD4 cell counts at least 200 cells/microl. Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003-2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/microl.
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            HIV-Related Medical Admissions to a South African District Hospital Remain Frequent Despite Effective Antiretroviral Therapy Scale-Up

            Abstract The public sector scale-up of antiretroviral therapy (ART) in South Africa commenced in 2004. We aimed to describe the hospital-level disease burden and factors contributing to morbidity and mortality among hospitalized HIV-positive patients in the era of widespread ART availability. Between June 2012 and October 2013, unselected patients admitted to medical wards at a public sector district hospital in Cape Town were enrolled in this cross-sectional study with prospective follow-up. HIV testing was systematically offered and HIV-infected patients were systematically screened for TB. The spectrum of admission diagnoses among HIV-positive patients was documented, vital status at 90 and 180 days ascertained and factors independently associated with death determined. Among 1018 medical admissions, HIV status was ascertained in 99.5%: 60.1% (n = 609) were HIV-positive and 96.1% (n = 585) were enrolled. Of these, 84.4% were aware of their HIV-positive status before admission. ART status was naive in 35.7%, current in 45.0%, and interrupted in 19.3%. The most frequent primary clinical diagnoses were newly diagnosed TB (n = 196, 33.5%), other bacterial infection (n = 100, 17.1%), and acquired immunodeficiency syndrome (AIDS)-defining illnesses other than TB (n = 64, 10.9%). By 90 days follow-up, 175 (29.9%) required readmission and 78 (13.3%) died. Commonest causes of death were TB (37.2%) and other AIDS-defining illnesses (24.4%). Independent predictors of mortality were AIDS-defining illnesses other than TB, low hemoglobin, and impaired renal function. HIV still accounts for nearly two-thirds of medical admissions in this South African hospital and is associated with high mortality. Strategies to improve linkage to care, ART adherence/retention and TB prevention are key to reducing HIV-related hospitalizations in this setting.
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              High Proportions of Patients With Advanced HIV Are Antiretroviral Therapy Experienced: Hospitalization Outcomes From 2 Sub-Saharan African Sites

              Abstract Background Human immunodeficiency virus (HIV) remains an important cause of hospitalization and death in low- and middle- income countries. Yet morbidity and in-hospital mortality patterns remain poorly characterized, with prior antiretroviral therapy (ART) exposure and treatment failure status largely unknown. Methods We studied HIV-infected inpatients aged ≥13 years from cohorts in Kenya and the Democratic Republic of Congo (DRC), assessing clinical and demographic characteristics and hospitalization outcomes. Kenyan inpatients were prospectively enrolled during hospitalization; identical retrospective data were extracted for Congolese patients meeting the study criteria using routine medical information. Results Among 338 HIV-infected patients in Kenya and 411 in DRC, 83.7% (95% confidence interval [CI], 79.4%–87.3%) and 97.3% (95% CI, 95.2%–98.5%), were admitted with advanced disease (defined as CD4 <200 cells/µL or World Health Organization stage 3/4 illness). Among inpatients with advanced HIV, 35.4% and 21.7% were ART-naive at admission. Patients under care had a median time of 44.1 (interquartile range [IQR], 18.4–90.5) months and 55.9 (IQR, 28.1–99.6) months on treatment; 17.2% (95% CI, 13.5%–21.6%) and 29.6% (95% CI, 25.4%–34.3%) died, 25.9% (95% CI, 16.0%–39.0%) and 22.5% (95% CI, 15.8%–31.0%) of these within 48 hours. Conclusions Across 2 diverse clinical contexts in sub-Saharan Africa, advanced HIV inpatients were frequently admitted with low CD4 counts, often failing first-line ART. Earlier identification of treatment failure and rapid switching to second-line ART are needed.
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                Author and article information

                Contributors
                tbarak@bidmc.harvard.edu
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                18 December 2019
                December 2019
                : 22
                : 12 ( doiID: 10.1002/jia2.v22.12 )
                : e25428
                Affiliations
                [ 1 ] Botswana‐Harvard AIDS Institute Partnership Gaborone Botswana
                [ 2 ] Department of Medicine Beth Israel Deaconess Medical Center Boston MA USA
                [ 3 ] Department of Medicine Scottish Livingstone Hospital Molepolole Botswana
                [ 4 ] Department of Obstetrics and Gynecology Beth Israel Deaconess Medical Center Boston MA USA
                [ 5 ] Nuffield Department of Population Health University of Oxford Oxford United Kingdom
                [ 6 ] Division of Global Health & Equity Brigham & Women's Hospital Boston MA USA
                [ 7 ] Division of Infectious Disease Beth Israel Deaconess Medical Center Boston MA USA
                [ 8 ] Department of Genitourinary Medicine Western Health and Social Care Trust Londonderry United Kingdom
                [ 9 ] Department of Immunology and Infectious Diseases Harvard T.H. Chan School of Public Health Boston MA USA
                Author notes
                [*] [* ] Corresponding author: Tomer Barak, Botswana Harvard Partnership, P Bag BO 320, Gaborone, Botswana. Tel: +267 7480 5920. ( tbarak@ 123456bidmc.harvard.edu )

                Author information
                https://orcid.org/0000-0002-2242-1389
                https://orcid.org/0000-0002-2048-3973
                https://orcid.org/0000-0001-5707-421X
                https://orcid.org/0000-0002-9280-5273
                https://orcid.org/0000-0003-0017-2438
                https://orcid.org/0000-0002-5384-9716
                https://orcid.org/0000-0002-4832-6275
                Article
                JIA225428
                10.1002/jia2.25428
                6918506
                31850683
                1983c02c-e64b-4ab5-b75b-3a35edca5243
                © 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 March 2019
                : 08 November 2019
                Page count
                Figures: 0, Tables: 5, Pages: 8, Words: 7186
                Funding
                Funded by: National Institutes of Health , open-funder-registry 10.13039/100000002;
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                December 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.3 mode:remove_FC converted:18.12.2019

                Infectious disease & Microbiology
                hiv,mortality,inpatient,hospital,botswana,africa
                Infectious disease & Microbiology
                hiv, mortality, inpatient, hospital, botswana, africa

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