Predictors of human immunodeficiency virus (HIV) infection in primary care among adults living in developed countries: a systematic review

Predictors of human immunodeficiency virus (HIV) infection in primary care among adults living in... Background: Early diagnosis of human immunodeficiency virus (HIV) is important because antiretroviral therapies are more effective if infected individuals are diagnosed early. Diagnosis of HIV relies on laboratory testing and determining the demographic and clinical characteristics of undiagnosed HIV-infected patients may be useful in identifying patients for testing. This systematic review aims to identify characteristics of HIV-infected adults prior to diagnosis that could be used in a prediction model for early detection of patients for HIV testing in UK primary care. Methods: The population of interest was adults aged ≥ 18 years in developed countries. The exposures were demographic, socio-economic or clinical characteristics associated with the outcome, laboratory confirmed HIV/ AIDS infection. Observational studies with a comparator group were included in the systematic review. Electronic searches for articles from January 1995 to April 2016 were conducted on online databases of EMBASE, MEDLINE, The Cochrane Library and grey literature. Two reviewers selected studies for inclusion. A checklist was developed for quality assessment, and a data extraction form was created to collate data from selected studies. Results: Full-text screening of 429 articles identified 17 cohort and case-control studies, from 26,819 retrieved articles. Demographic and socio-economic characteristics associated with HIV infection included age, gender and measures of deprivation. Lifestyle choices identified were drug use, binge-drinking, number of lifetime partners and having a partner with risky behaviour. Eighteen clinical features and comorbid conditions identified in this systematic review are included in the 51 conditions listed in the British HIV Association guidelines. Additional clinical features and comorbid conditions identified but not specified in the guidelines included hyperlipidemia, hypertension, minor trauma and diabetes. Conclusion: This systematic review consolidates existing scientific evidence on characteristics of HIV-infected individuals that could be used to inform decision making in prognostic model development. Further exploration of availability of some of the demographic and behavioural predictors of HIV, such as ethnicity, number of lifetime partners and partner characteristics, in primary care records will be required to determine whether they can be applied in the prediction model. Keywords: Acquired immuno-deficiency syndrome, Antiretroviral therapies, Diagnosis, Human immunodeficiency virus, Patient characteristics, HIV predictors, Primary care * Correspondence: bnr546@bham.ac.uk Institute of Applied Health Research, University of Birmingham, Birmingham B15 2TT, UK Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 2 of 15 Background that one in three patients that presented at least one Human immunodeficiency virus (HIV) is a retroviral HIV-related symptoms to their GPs was consequently infection that weakens the immune system and is a subse- diagnosed with HIV by their GP [18]. Therefore, primary quent causative agent of acquired immuno-deficiency carehas arole toplay in increasinguptakeofHIV syndrome (AIDS) [1, 2]. The virus is transmitted through diagnostic testing since nearly all the UK population is the exchange of a variety of bodily fluids mainly sexually, registered with a GP [19]. HIV testing in general practices perinatal and blood-borne [2, 3]. HIV/AIDS is one of the can be done by either sending blood samples for laboratory highest contributors to morbidity and the sixth leading testing or conducting combined HIV antibody and protein cause of mortality worldwide [2, 4]. The World Health 24 (P24) antigen tests followed by laboratory confirmation Organization (WHO) estimated that 1.5 million people [9]. However, among those who visit their GP, a challenge died of HIV/AIDS-related diseases and 36.7 million lived is the fact that HIV/AIDS has many signs and symptoms with HIV worldwide, in 2015 [5]. In 2015, it was estimated such as rashes, weight loss and respiratory infections and that 594 deaths were associated with HIV\AIDS in England theseare not specifictoHIV/AIDS. and 101,200 people were estimated to live with HIV in Current UK guidelines from British HIV Association the UK [6]. (BHIVA) recommend HIV testing to individuals from Thelifeexpectancyof HIV-infectedindividuals has high-risk groups, those with symptoms indicative of HIV increased over the years and is approaching that for the or where HIV forms part of the diagnosis [20]. However, general population [7, 8]. This is a result of the effectiveness approximately three-quarters of patients consult their of antiretroviral therapies (ART) that has led to most indi- GPs in the period prior to diagnosis may not present these viduals coping with HIV infection as a chronic condition indicator symptoms and diagnoses [17]. This suggests that rather than an illness inevitably leading to death [9]. The these currently recommended predictive factors are of use of ARTs has led to a better quality of life for infected limited use in the identification of possible HIV-infected individuals and a reduction in morbidity and mortality [4]. individuals. In the 1980s/1990s, more focus was placed on HIV The methods used in routine HIV testing either involve prevention strategies and treatment of symptomatic use of screening assays on blood for laboratory testing or diseases but due to the benefits of ART, the emphasis rapid tests conducted on samples from a finger-prick or has now moved to earlier HIV diagnosis [10]. WHO mouth swab at point of care. The commonly used and developed a strategy aimed at reducing new HIV infections, recommended first-line assays test for HIV antibodies and AIDS-related mortality and discrimination to zero with the HIV p24 antigens simultaneously [9, 20]. These assays one of the HIV strategies being optimisation of ‘HIV pre- can be utilised within a month of HIV infection [9, 20]. vention, diagnosis, treatment and care outcomes’ [11]. The sensitivity of these assay tests ranges from 99.8–100% The CD4 count is an indicator of immunosuppression and the specificity ranges from 99.4–100% [21, 22]. in an individual infected with HIV [9]. Early diagnosis of Point-of-care tests (POCTs) are rapid testing devices that people with HIV (cluster of differentiation 4 (CD4) > diagnose HIV within 15 min. However, such tests have 350/mm ) improves the effectiveness of antiretroviral lower specificity in comparison to laboratory tests, thereby therapies, and additionally, the treatment and advice giving significantly high proportion of false positives, provided reduces onward transmission, thereby making especially when used in low prevalence settings [9]. It is late diagnosis of HIV (CD4 < 350/mm ) an important therefore possible to test for and diagnose HIV using public health concern [12, 13]. Furthermore, early diagnosis simple blood tests with few false positives and false of HIV and earlier use of therapies reduce health and social negatives. care costs by preventing illness associated with HIV [4, 14]. The UK primary care clinicians need to identify patients On the other hand, delayed diagnosis of HIV to late stages who should be offered HIV testing. A systematic review is (CD4 < 350/mm ) leads to worse prognosis for the patient therefore necessary to identify demographic, lifestyle, due to irreversible immunologic damage and associated clinical and laboratory characteristics of patients which problems [13, 15]. might be associated with HIV infection in primary care. Public Health England estimated that out of the 101,200 The identified characteristics will be investigated to deter- individuals living with HIV in 2015, 6095 were newly diag- mine if they are documented in electronic primary care nosed and 13% were unaware of their HIV status [6]. In records and whether they can be used to predict which that year, 39% of people that were newly diagnosed with primary care patients are likely to have HIV infection. HIV in the UK were detected late (CD4 < 350/mm ), which This systematic review identifies, critically evaluates and is an intolerably high proportion [6]. Meanwhile, evidence interprets available evidence related to the demographic, shows that about 33% of patients that are diagnosed with lifestyle, clinical and laboratory characteristics associated HIV in the UK would have seen a general practitioner with HIV/AIDS infection in adults in the developed (GP) within the previous year [9, 16, 17]. One study found world [23, 24]. Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 3 of 15 Methods America (USA and Canada), Australia and New Zealand. This systematic review conforms to the requirements of Studies which include children only are excluded. the Preferred Reporting Items for Systematic Reviews and Meta-analyses (Additional file 1, PRISMA) [25]. The Selection procedure methods were detailed in a published protocol, but a Two reviewers independently selected articles in the first summary is included in this section [26]. The PROSPERO and second screening of articles. The first screening registration number for the protocol is CRD42016042427. checked titles/abstracts to find out if articles addressed the review question and fulfilled the inclusion and exclu- sion criteria (Additional file 3: Appendix II). The second Review question screening was the full article review. Differences between This systematic review systematically identifies and the reviewers were resolved through discussions. summarises evidence on characteristics of HIV-infected adults which could be used in a prediction model for Quality assessment and data extraction early detection of HIV in primary care. Quality assessment was done using a checklist for cohort and case-control studies modified from the Scottish The review question is: Intercollegiate Guidelines Network (SIGN) [29]. A data extraction form was developed to collate data What demographic, lifestyle, clinical and laboratory from selected articles. Tabulation and narrative of the characteristics are associated with HIV infection in adults results were produced, and the tabulation contains aged 18 years and over? description of the articles (the author, publication year, the study design, number of participants, population Population, exposure and outcome under study and outcome). Studies selected included human participants ≥ 18 years. Exposures may be demographic, socio-economic or Results clinical risk factors or characteristics associated with Selection procedure HIV infection. The comparison group is either people A total of 26,819 hits were returned from the database without risk factors or no comparison group. The out- searches and NICE and DH, 6173 duplicates were come is laboratory-confirmed HIV/AIDS infection. removed and 20,646 articles were pre-screened (Fig. 1). The first review resulted in selection of 429 articles Study design using titles/abstracts. A discussion was held to agree on This review considers observational (analytical) studies, the articles selected. The reviewers independently selected comparing groups and produces predictive values or suitable articles using full text and a second discussion likelihood ratios (case-control and cohort, both retro- was held. The reviewers agreed on 17 articles: 11 cohort spective and prospective studies) [27]. and 6 case-control studies. Search strategy Quality of studies Studies are identified via electronic searches of EMBASE All 11 cohort studies were of acceptable standard, but (Ovid), MEDLINE (Ovid), The Cochrane Library (Wiley) only 2 were of high quality, in terms of participant and the unpublished grey literature (SIGLE, Google recruitment, sample size and how they dealt with bias. Scholar and BASE). Additional searches are conducted The other articles were not clear about how they dealt on abstracts or conference proceedings using Web of with confounding factors (Table 1). All 6 case-control Science Conference Proceedings Citation Index (CPCI), studies were of acceptable standard, and half of them Global Index Medicus, guidelines (NICE, DH) and reference were of high quality, in terms of participant recruitment, searching [28]. There were no language restrictions, and all sample size and how they dealt with bias. studies published from year 1995 to April 2016 were included. The search terms used in Ovid MEDLINE Study characteristics (Additional file 2: Appendix I) are adjusted to suit The cohort studies were conducted in the UK (3), searches in other databases. References were searched Ireland (1), Australia (1) and USA (6). The number of and stored using the Refworks referencing programme. participants ranged from 32 to over 20,000 with most studies focusing on patients aged ≥ 18 years. The study Inclusion/exclusion criteria duration ranged from 1 to 5 years, but some of the studies To ensure generalisability to a UK setting, only studies did not state follow-up intervals (Table 1). undertaken in the following developed countries are The case-control studies were conducted in the UK included in this review: Europe (all countries) and North (1), Netherlands (1), the USA (2) and Canada (2). In Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 4 of 15 Fig. 1 PRISMA 2009 flow diagram total, they included 1412 cases and 3423 controls. The significant association with the risk of HIV infection study duration ranged from 1 to 12 years with a 6-month [30, 31]. Two studies showed conflicting evidence on follow-up for most of the studies. the increased risk of HIV infection associated with country of birth; one study from the USA showed that Identified predictors of HIV infection being born in the USA was associated with 1.76 times The predictors of HIV identified were categorised into the risk [30], but a study from Australia showed that demographic and socio-economic, behavioural or life- being born in Australia had a non-significant risk [35]. style, clinical features and comorbidities. Statistically Socio-economic conditions associated with increased risk significant characteristics or those with highest percentages of HIV identified were (i) poverty in urban but not in rural were included. areas (1 study) [37], (ii) annual income under $10,000 having 13 times the risk (1 study) [30], (iii) unemployment (1 study) Demography and socio-economic [30], (iv) housing problems (1 study) [30]and (v)not being The significant demographic characteristics (Table 2) a high school graduate or having low education attainment associated with HIV infection were (i) homosexuals and/or (2 studies); 2.2 times the risk [30, 38]. bisexuals, mainly men who have sex with men (MSM) (5 studies) 1.8 to 2.7 times risk [30–34], (ii) black ethnicity Behavioural characteristics (1 study); 6.8 times risk [30] and (iii) age ranges (3 studies), Behavioural characteristics (Table 3) associated with an mainly between 27 and 40 years with up to 11.5 times the increased risk of HIV infection can be categorised into risk [31, 35, 36]. Two studies revealed that gender had no personal lifestyle, partner lifestyle and effects of life events. Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 5 of 15 Table 1 Data extract and quality assessment summary: cohort and case-control studies Study Design Population, Outcome: duration Study addresses an Participants being Indicate how Main potential How well was the study setting and follow-up appropriate and studied are selected many people confounders done to minimise the risk clearly focused from the same source participated identified and of bias or confounding? question populations accounted for 1. Joore I.K. et al., Case-control study 102 cases and 299 HIV infection: 2002–2012 Yes Yes Yes Cannot say + (2015) [42] controls, Amsterdam, Netherlands 2. Damery S. et al. Case-control study 939 cases and 2576 HIV/AIDS diagnosis: Yes Yes Yes Yes ++ (2013) [17] control, UK Jan 1989–Sept 2010 3. Szerlip M.A. Case-control study Older patients aged Diagnosis of HIV infection: Yes Yes Yes Cannot say + et al. (2005) [39] (retrospective) 55 years and over (53 6 months interval up to cases and 106 controls), 12 months New Orleans, USA 4. Ellerbrock T.V. Case-control study 217 cases 395 controls, HIV diagnosis: 1998–2000 Cannot say Yes Yes Cannot say + (2004) [30] FL, USA 5. Burchell, A.N. Case-control study Gay and bisexual men HIV infection: 1998–2006 Yes Yes Yes Yes ++ (2010) 123 cases and 240 controls, Ontario, Canada 6. Burchell, A. N. Case-control study Adults aged 18 years Diagnosed HIV infection: Yes Yes Yes Yes ++ (2003) [41] and over 80 cases June 1998–Dec 2001 (seroconverts) and 106 controls, Ontario, Canada 7. Hodder, S.L. Cohort study N = 2099 (women aged HIV prevalence and Yes Yes Yes Yes + (2013) [36] (prospective) 18–44 with 1 or more incidence: 2009–2010 with personal or partner risk 6-month follow-up to factors), USA 12 months 8. Moran. J. Cohort study N = 1404 HIV infection: 2008–2011 Yes Cannot say Yes No + (2012) [34] Ireland 9. Desai M. Cohort study N = 328 HIV infection: Yes Cannot say Yes No + (2012) [38] UK Sept 2010–Dec 2011 10. Guy R.J. Cohort study N = 7857 (MSM) Victoria, HIV positivity: Yes Yes Yes Cannot say + (2011) [35] Australia Apr 2006–Jun 2009 11. Krauskopf K. Cohort study N = 643 (HIV-infected HIV infection: Yes Yes Yes Yes ++ (2011) [45] and at-risk men aged 2001–2006 6-month 49 years and older), follow-up Bronx, NY, USA 12. Niyonsenga T Cohort study N = 20,528 (all cases AIDS/HIV incidence: 1998– Yes Cannot say Yes Cannot say + (2013) [37] with HIV/AIDS 2002 diagnosis), FL, USA 13. Ross, J. D. Cohort study N = 8466 (population HIV positive results: Yes Yes (1997) [31] aged 16 and over), Jan 1989–Dec 1993 Lothian and Glasgow region of Scotland Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 6 of 15 Table 1 Data extract and quality assessment summary: cohort and case-control studies (Continued) Study Design Population, Outcome: duration Study addresses an Participants being Indicate how Main potential How well was the study setting and follow-up appropriate and studied are selected many people confounders done to minimise the risk clearly focused from the same source participated identified and of bias or confounding? question populations accounted for 14. Gordon S. M. Cohort study N = 32 (HIV-positive HIV positivity: Yes No Yes No + (1995) [32] patients aged ≥ 60) Jan 1985–July 1992 Atlanta, GA, USA 15. Marder K. Cohort study Intravenous drug users HIV infection: recruited Yes Yes Yes Yes ++ (1995) [44] (prospective) (99 HIV + ve patients 124 1988 and followed up for HIV − ve patients), 3.5 years and 6-month New York City, USA follow-up 16. Hafner J. W. Cohort study N = 344 Albuquerque, HIV diagnosis: 19-month Yes Yes Cannot say + (1997) [33] (retrospective) NM, USA period July 1993–Jan 1995 17. Landau R. Cohort study N = 133 (A&E patients HIV infection: 1991–1994 Yes Yes Yes No + (1997) [43] (retrospective) aware and unaware of HIV status), London, UK Modified from Scottish Intercollegiate Guidelines Network (SIGN) Minimise risk of bias or cofounding: high quality (++) □ acceptable (+) □ unacceptable—reject 0 Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 7 of 15 Table 2 Demographic characteristics identified in selected studies Studies Ellerbrock 2004 [30] Guy 2011 [35] Hodder 2013 [36] Ross 1997 [31] Niyonsenga 2013 [37] Gordon 1995 [32] Desai 2012 [38] Hafner 1997 [33] Moran 2012 [34] OR OR OR OR CC** % % % Demographic Age Reference group < 30 y 18–26 years 21–25 years 26–30 1.7 (1.05–2.8) 27–33 5.83 (1.22–27.96) 30–39 1.91 (1.27-2.87) 31–35 0.3* 34+ 11.54 (2.71–49.05) 36–40 1.6* 40+ 1.81 (1.19-2.75) Ethnicity Black race 6.77 (4.17–11) (Reference = white) Aboriginal or Torres 1.68* (0.41–6.94) Strait Islander Country of Born in USA 1.76 (1.22–2.53) birth Born in Australia 1.42* (1.00–2.02) Sexuality Homosexual/ 1.79* (0.67–4.79) 2.7 (1.5–4.8) 37% 57% 61% bisexual Heterosexual 1.00 1.0 3% 28% Socio-economic factor Housing problems 17% Poverty index in rural areas − 0.25* Poverty index in urban areas 0.58 Annual income < $10,000 13.2 (7.91–22) Farmworker 2.09 (1.47–2.96) Unemployed 5.08 (3.18–8.14) 26% Education beyond high school 0.43* (0.15–1.24) Not a high school graduate 2.15 (1.48–3.1) NB % do not add up to 100% because they are provided for all risk factors *Not statistically significant **Correlation coefficient Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 8 of 15 Table 3 Behavioural or lifestyle––personal choices identified in selected studies Predictor Ellerbrock Gordon Guy 2011 [35] Hafner Hodder Moran Ross Desai Szerlip 2004 [30] 1995 [32] 1997 [33] 2013 [36] 2012 [34] 1997 [31] 2012 [38] 2005 [39] OR % OR % OR % OR % OR Injected drugs users 21.1 (4.89–90.9) 18% 2.97 (1.77–5.00) 30% 2.71 (1.33–5.53) 10% 2.3 (1.5–3.5) Ever smoked crack 22.8 (12.6–41.5) cocaine Binge-drinking or 1.57* (0.74–3.33) 12.8 (1.65–99) alcohol misuse Substance use 2.52 (1.22–5.21) 22% (combined)** Current smokers 25% Unsafe sex 1.84 (1.6– 3.20) 60% HIV positive partner 3.24 (1.47–7.11) Sex with drug user 17.2 (7.18–40.9) Contact abroad 2* Ever exchanged money 19.3 (11.2–33.2) or drugs for sex Male anal sex in the last 1.63 (1.13– 2.35) ≥ 6 months Multiple life partners M: 5.51 (3.18–9.55) F: 19.8 (8.81–44.2) Obesity 10% *Not statistically significant **Includes drug use or binge-drinking Personal lifestyle choices identified were (i) injecting drugs symptoms including fever/chills and cough (3 studies); 4.5 (7 studies); 2 to 21 times the risk [30, 31][32–36], (ii) times the risk [33, 39, 41], (ii) rash (1 study); 4.5 times the smoking crack cocaine (1 study); 22.8 times the risk risk [39], (iii) weight loss (2 studies); 13 to 39 times the [30], (iii) being a current smoker (1 study) [38], (iv) risk [17, 41], (iv) diarrhoea (2 studies); 2 to 4.4 times binge-drinking (1 study); 12.8 times the risk [34], (v) the risk [17, 41] and one study identified abdominal exchanging money or drugs for sex (1 study); 19 times pain, minor trauma and nausea/vomiting as the condition the risk [30], (vi) male anal sex (1 study); 1.6 times the affecting 5–6% of the HIV-positive patients [33]. risk [35] and (vii) being obese (1 study) [30]. Personal sexual behaviours identified were unsafe sex (2 studies); Comorbidities associated with HIV 1.8 times the risk [35, 38] and having multiple sex partners The clinical indicator conditions (Table 4) were categorised (1 study); 5.5 times the risk for males with ≥ 10 and 20 into the following: respiratory, dermatology, neurology, times the risk for females with ≥ 3 lifetime partners [30]. gastroenterology, gynaecology, haematology, ophthalmology, Partner-related behaviours identified were (i) HIV-positive ear, nose and throat (ENT) and other (not classified). partner(2studies); 3and 8times therisk[35, 36], (ii) The respiratory conditions identified were pneumonia partner’s use of illicit drugs (2 studies); 1.57 and 17 times (2 studies); 8 and 48 times the risk [17, 41] and pneumo- [30, 36], (iii) partner’s alcohol dependence/binge-drinking cystis in 52% of the HIV-infected patients (1 study) [42]. (1 study); 1.4 to 1.8 times the risk [39]. The dermatological conditions identified were psoriasis One study revealed risk-associated stressful events in (2 studies); 2.6 to 3 times the risk [17, 41] and herpes men having sex with men to be; (i) the number of stressful zoster (2 studies); 10.9 and 25.4 times the risk [17, 41]. events, (ii) events occur in ages under 30 years associated The evidence revealed that HIV infection was signifi- with 7 times the risk, (iii) type of stressful events such as cantly associated with peripheral neuropathy (1 study); bereavement and death of close friend and financial crisis 15.9 times the risk [41] and neurologic disabilities cranial and relationship breakdown (romantic and other relations); nerve abnormalities and fine limb movement (1 study); 3times therisk [40]. 2.4 times the risk in women and 1.9 times the risk in men [43]. The gastroenterological conditions identified were Clinical features oral candidiasis (2 studies); 7.1 and 29.4 times the risk Evidence from 4 studies (Table 4) revealed that HIV [17, 41], hepatitis B (2 studies); 8.3 and 11.5 times the infection was associated with clinical features: (i) flu-like risk [44, 41] and liver diseases (1 study), affecting 22% Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 9 of 15 Table 4 Clinical features and comorbidities identified in selected studies Condition Damery Joore Hafner Marder Burchell Szerlip Krauskopf Landau Hodder Guy Ellerbrock 2013 [17] 2015 [42] 1997 [33] 1995 [44] 2003 [41] 2005 [39] 2011 [45] 1997 [43] 2013 [36] 2011 [35] 2004 [30] OR (CI) OR (CI) % OR % & OR OR % % OR OR OR Clinical features Weight loss 13.4 39.6 (5.15–6.7) (6.2–∞) Fever or chills 4.5* 13% (0.5–54.3) Cough 7% Flu-like symptoms 76% Diarrhoea 2* (0.2–17.4) Diarrhoea one only 3.7* consultation (0.9–5.48) Diarrhoea two 4.4 consultation (2.3–2.81) Abdominal pain 5% Minor trauma 6% Nausea/vomiting 6% Rash 4.5 Number of HIV One 11.7 indicator conditions (6–23.6) Two 77.5 (18.2–700.8) Comorbidities Respiratory Pneumonia 47.7 8.3 (3.54–52) (2–49.8) Pneumocystis carinii 52% Dermatology Psoriasis 2.9* (0.1–∞) Psoriasis—one 2.6 consultation only (1.69–1.5) Psoriasis—two 3 consultations (1.38–2.5) Herpes zoster 25.4 10.9 (5.76–14.2) (2–108.9) Neurology Peripheral neuropathy 15.9 (2–∞) Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 10 of 15 Table 4 Clinical features and comorbidities identified in selected studies (Continued) Condition Damery Joore Hafner Marder Burchell Szerlip Krauskopf Landau Hodder Guy Ellerbrock 2013 [17] 2015 [42] 1997 [33] 1995 [44] 2003 [41] 2005 [39] 2011 [45] 1997 [43] 2013 [36] 2011 [35] 2004 [30] OR (CI) OR (CI) % OR % & OR OR % % OR OR OR Neurologic disability 2.4 in women Neurologic disability 1.9 in men (1.1–3.2) Gastroenterology Oral candidiasis 29.4 7.1* (4.57–21.8) (0.6–∞) Hepatitis B 11.5 8.3 (1.2–∞) (2.65–26.2) Chronic liver disease 22% (15%–29%) Oncology Non-Hodgkin’s lymphoma 12.6 (2.13–15) Lymphogranuloma venereum 7.1* (0.6–∞) Gynaecology Cervical dysplasia 2.9* (0.4–232.4) Condyloma acuminata 12.1 (1.2–600.9) Haematology Leucocytopenia 11.5 (1.2–∞) Blood dyscrasia 5.7 (2.44–4) ENT Lymphadenopathy 11.3 29.8 (5.15–5.3) (4.4–∞) Parotitis 8.6 (1.68–11) Other Mononucleosis-like illness 6.2 (1.6–29) Pyrexia of unknown origin 7.2 (4.05–3.5) Hyperlipidemia 25% (17%–32%) Hypertension 10% (4%–16%) Diabetes 10% (5%–14%) Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 11 of 15 Table 4 Clinical features and comorbidities identified in selected studies (Continued) Condition Damery Joore Hafner Marder Burchell Szerlip Krauskopf Landau Hodder Guy Ellerbrock 2013 [17] 2015 [42] 1997 [33] 1995 [44] 2003 [41] 2005 [39] 2011 [45] 1997 [43] 2013 [36] 2011 [35] 2004 [30] OR (CI) OR (CI) % OR % & OR OR % % OR OR OR Sexually Transmitted 10.8 10.1 (3.39–30.12) 10.1 Infection (STI) (3.38–7.6) (6.89–14.9) STI diagnosis ≤ 2 years 2.72 (1.77–4.2) ≤ 14 days 3.19 (2.05–4.96) Number of STIs per patient One 14.6 (5.5–45.6) ≥ 2 37.9 (5.6-∞) Syphilis 39.3 7.35 12.7 (5.7–1703.9) (2.52–21.5) (7.28–22.3) Seropositive for syphilis* 7.29 (4.15–12.8) Infectious Syphilis ≤ 2 years 3.86 diagnosis (1.99–7.5) ≤ 14 days 4.9 (2.51–9.56) Chlamydia 11.8 (3–67.5) Chlamydia diagnosis ≤ 2 years 2.31 (1.4–3.81) ≤ 14 days 2.62 (1.56–4.39) Gonorrhoea 15.9 6.51 (2–∞) (4.4–9.65) Genital herpes 2.9* (0.1–∞) *Not statistically significant ∞ Means infinity upper limit Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 12 of 15 Table 5 Predictors identified and availability in electronic primary care records Category of predictor Predictor of HIV infection Likelihood of being recorded in primary care records Sociodemographic Age Present for all patients Gender Present for all patients Social status Inferred from postcode Poverty index Present as deprivation quintile Annual income Inferred from prescription payments, benefits Employment status Likely to be poorly recorded Sexual orientation Require further investigation Not a high school graduate Not present Country of birth Not present Ethnicity Present for some patients Behavioural Smoking status Very likely to be present Drug use Present for some patients Binge-drinking or alcohol misuse Present for some patients Obesity Very likely to be present Contact abroad Might be present Stressful events Present for some patients Unsafe sex Likely not present Ever exchanged money or drugs for sex Likely not present Male anal sex Likely not present Number of lifetime partners Likely not present Partner characteristics Likely not present Clinical and comorbid conditions Weight loss Likely to be present Fever or chills Likely to be present Cough Likely to be present Flu like symptoms Likely to be present Diarrhoea Likely to be present Abdominal pain Likely to be present Minor trauma Likely to be present Nausea/vomiting Likely to be present Rash Likely to be present Pneumonia Likely to be present Pneumocystis carinii Likely to be present Psoriasis Likely to be present Herpes zoster Likely to be present Peripheral neuropathy Likely to be present Neurologic disability Likely to be present Oral candidiasis Likely to be present Hepatitis B Likely to be present Chronic liver disease Likely to be present Non-Hodgkin’s lymphoma Likely to be present Condyloma acuminata Likely to be present Leucocytopenia Likely to be present Blood dyscrasia Likely to be present Lymphadenopathy Likely to be present Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 13 of 15 Table 5 Predictors identified and availability in electronic primary care records (Continued) Category of predictor Predictor of HIV infection Likelihood of being recorded in primary care records Parotitis Likely to be present Mononucleosis-like illness Likely to be present Pyrexia of unknown origin Likely to be present Hyperlipidemia Likely to be present Hypertension Likely to be present Diabetes Likely to be present Sexually transmitted infection Likely to be present Syphilis Likely to be present Chlamydia Likely to be present Gonorrhoea Likely to be present Genital herpes Likely to be present of the HIV-infected patients [45]. One oncological condi- further investigation to assess if they can be reliably tions identified was Non-Hodgkin’s lymphoma (1 study); identified and included in a future clinical prediction 12.6 times the risk [17]. model (Table 5). Only one study identified gynaecological conditions The demographic and socio-economic predictors associated with increased risk of HIV diagnosis and identified and available in primary care records are age, condyloma acuminata; 12.1 times the risk [41]. The two gender and deprivation quintile as a proxy for some of haematological conditions identified in the studies were the socio-economic predictors. Behavioural predictors leukocytopenia (1 study); 11.5 times the risk [41]and identified and available in electronic health records are blood dyscrasia (1 study); 5.7 times the risk [17]. ENT drug use, binge-drinking or alcohol misuse, current conditions identified were lymphadenopathy (2 studies); smokers and obesity. All the clinical features and comorbid 11.3 and 29.8 times the risk [17, 41] and parotitis (1 study); diseases identified are most probably available in electronic 8.6 times the risk [17]. health records (Table 5). The other conditions identified were mononucleosis-like Some of the demographic, socio-economic and behav- illness (1 study); 6.2 times the risk [41], pyrexia of unknown ioural predictors identified in literature, such as ethnicity, origin (1 study); 7.2 times the risk [17]and onestudy which country of birth, income and education levels, might be had 10–25% of the HIV-infected patients with hyperlipid- available in primary care records and therefore require emia, hypertension and diabetes [45]. The other conditions further investigation on completeness. identified were sexually transmitted infections (5 studies), 2.7to37.9times therisk[17, 30, 35, 44, 41], and the Limitations following infections were identified: (i) syphilis (3 studies), This systematic review focused on studies conducted in 3.9 to 39.3 times the risk [30, 44, 41]; (ii) chlamydia (2 developed countries whereas most of the studies on HIV studies), 2.3 to 11.8 times the risk [30, 35]; (iii) gonorrhoea predictors were conducted in developing countries, (2 studies), 6.5 to 15.9 times the risk [30, 41]and (iv) mostly in Africa. Most of the studies conducted on HIV genitalherpes(1study), 2.9times therisk[41]. were case studies, qualitative studies and cross-sectional studies which are not suitable in identifying risk factors. Some of the studies identified in this systematic review Discussion reported percentages rather than odds ratio in their results This systematic review identified 10 demographic and making the interpretation of risk association difficult. socio-economic characteristics, 11 behavioural character- istics, and 27 clinical features and comorbid conditions Conclusion that are significantly associated with HIV infection. This systematic review revealed existing scientific evidence The purpose of this systematic review was to identify on predictors of HIV that can be used to inform decision predictors of HIV infection available in electronic patient making in prognostic model development [46]. Only 2 records that could be incorporated in a prediction model to demographic and socio-economic characteristics (age and identify primary care patients with undiagnosed HIV. gender) and 4 behavioural characteristics (drugs use, Candidate predictors identified are either routinely re- binge-drinking or alcohol misuse, current smokers and corded in electronic primary care records or require obesity) identified in literature are available in electronic Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 14 of 15 primary-care records. The other 8 demographic and Received: 3 January 2018 Accepted: 11 May 2018 socio-economic and 7 behavioural characteristics require further investigation on completeness or if they are not References available at all. Further exploration will determine whether 1. Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb the characteristics can be applied in a model. 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Marder K, Liu XH, Stern Y, Malouf R, Dooneief G, Bell K, Todak G, Joseph M, Sorrell S, Sadr WE, Williams JBW, Ehrhardt A, Stein Z, Gorman J. Risk of human-immunodeficiency-virus type 1-related neurologic disease in a cohort of intravenous-drug-users. Arch Neurol. 1995;52(12):1174–82. 45. Krauskopf K, Federman DA, Mhango G, Klein RS. Association of HIV status and non-AIDS comorbid diagnoses in a cohort of older HIV-infected and at-risk men. J Gen Intern Med. 2011;26:s58. 46. Wright RW, Brand RA, Dunn W, Spindler KP. How to write a systematic review. Clin Orthop Relat Res. 2007;455:23–9. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Systematic Reviews Springer Journals

Predictors of human immunodeficiency virus (HIV) infection in primary care among adults living in developed countries: a systematic review

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Medicine & Public Health; Medicine/Public Health, general; Biomedicine, general; Statistics for Life Sciences, Medicine, Health Sciences
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Abstract

Background: Early diagnosis of human immunodeficiency virus (HIV) is important because antiretroviral therapies are more effective if infected individuals are diagnosed early. Diagnosis of HIV relies on laboratory testing and determining the demographic and clinical characteristics of undiagnosed HIV-infected patients may be useful in identifying patients for testing. This systematic review aims to identify characteristics of HIV-infected adults prior to diagnosis that could be used in a prediction model for early detection of patients for HIV testing in UK primary care. Methods: The population of interest was adults aged ≥ 18 years in developed countries. The exposures were demographic, socio-economic or clinical characteristics associated with the outcome, laboratory confirmed HIV/ AIDS infection. Observational studies with a comparator group were included in the systematic review. Electronic searches for articles from January 1995 to April 2016 were conducted on online databases of EMBASE, MEDLINE, The Cochrane Library and grey literature. Two reviewers selected studies for inclusion. A checklist was developed for quality assessment, and a data extraction form was created to collate data from selected studies. Results: Full-text screening of 429 articles identified 17 cohort and case-control studies, from 26,819 retrieved articles. Demographic and socio-economic characteristics associated with HIV infection included age, gender and measures of deprivation. Lifestyle choices identified were drug use, binge-drinking, number of lifetime partners and having a partner with risky behaviour. Eighteen clinical features and comorbid conditions identified in this systematic review are included in the 51 conditions listed in the British HIV Association guidelines. Additional clinical features and comorbid conditions identified but not specified in the guidelines included hyperlipidemia, hypertension, minor trauma and diabetes. Conclusion: This systematic review consolidates existing scientific evidence on characteristics of HIV-infected individuals that could be used to inform decision making in prognostic model development. Further exploration of availability of some of the demographic and behavioural predictors of HIV, such as ethnicity, number of lifetime partners and partner characteristics, in primary care records will be required to determine whether they can be applied in the prediction model. Keywords: Acquired immuno-deficiency syndrome, Antiretroviral therapies, Diagnosis, Human immunodeficiency virus, Patient characteristics, HIV predictors, Primary care * Correspondence: bnr546@bham.ac.uk Institute of Applied Health Research, University of Birmingham, Birmingham B15 2TT, UK Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 2 of 15 Background that one in three patients that presented at least one Human immunodeficiency virus (HIV) is a retroviral HIV-related symptoms to their GPs was consequently infection that weakens the immune system and is a subse- diagnosed with HIV by their GP [18]. Therefore, primary quent causative agent of acquired immuno-deficiency carehas arole toplay in increasinguptakeofHIV syndrome (AIDS) [1, 2]. The virus is transmitted through diagnostic testing since nearly all the UK population is the exchange of a variety of bodily fluids mainly sexually, registered with a GP [19]. HIV testing in general practices perinatal and blood-borne [2, 3]. HIV/AIDS is one of the can be done by either sending blood samples for laboratory highest contributors to morbidity and the sixth leading testing or conducting combined HIV antibody and protein cause of mortality worldwide [2, 4]. The World Health 24 (P24) antigen tests followed by laboratory confirmation Organization (WHO) estimated that 1.5 million people [9]. However, among those who visit their GP, a challenge died of HIV/AIDS-related diseases and 36.7 million lived is the fact that HIV/AIDS has many signs and symptoms with HIV worldwide, in 2015 [5]. In 2015, it was estimated such as rashes, weight loss and respiratory infections and that 594 deaths were associated with HIV\AIDS in England theseare not specifictoHIV/AIDS. and 101,200 people were estimated to live with HIV in Current UK guidelines from British HIV Association the UK [6]. (BHIVA) recommend HIV testing to individuals from Thelifeexpectancyof HIV-infectedindividuals has high-risk groups, those with symptoms indicative of HIV increased over the years and is approaching that for the or where HIV forms part of the diagnosis [20]. However, general population [7, 8]. This is a result of the effectiveness approximately three-quarters of patients consult their of antiretroviral therapies (ART) that has led to most indi- GPs in the period prior to diagnosis may not present these viduals coping with HIV infection as a chronic condition indicator symptoms and diagnoses [17]. This suggests that rather than an illness inevitably leading to death [9]. The these currently recommended predictive factors are of use of ARTs has led to a better quality of life for infected limited use in the identification of possible HIV-infected individuals and a reduction in morbidity and mortality [4]. individuals. In the 1980s/1990s, more focus was placed on HIV The methods used in routine HIV testing either involve prevention strategies and treatment of symptomatic use of screening assays on blood for laboratory testing or diseases but due to the benefits of ART, the emphasis rapid tests conducted on samples from a finger-prick or has now moved to earlier HIV diagnosis [10]. WHO mouth swab at point of care. The commonly used and developed a strategy aimed at reducing new HIV infections, recommended first-line assays test for HIV antibodies and AIDS-related mortality and discrimination to zero with the HIV p24 antigens simultaneously [9, 20]. These assays one of the HIV strategies being optimisation of ‘HIV pre- can be utilised within a month of HIV infection [9, 20]. vention, diagnosis, treatment and care outcomes’ [11]. The sensitivity of these assay tests ranges from 99.8–100% The CD4 count is an indicator of immunosuppression and the specificity ranges from 99.4–100% [21, 22]. in an individual infected with HIV [9]. Early diagnosis of Point-of-care tests (POCTs) are rapid testing devices that people with HIV (cluster of differentiation 4 (CD4) > diagnose HIV within 15 min. However, such tests have 350/mm ) improves the effectiveness of antiretroviral lower specificity in comparison to laboratory tests, thereby therapies, and additionally, the treatment and advice giving significantly high proportion of false positives, provided reduces onward transmission, thereby making especially when used in low prevalence settings [9]. It is late diagnosis of HIV (CD4 < 350/mm ) an important therefore possible to test for and diagnose HIV using public health concern [12, 13]. Furthermore, early diagnosis simple blood tests with few false positives and false of HIV and earlier use of therapies reduce health and social negatives. care costs by preventing illness associated with HIV [4, 14]. The UK primary care clinicians need to identify patients On the other hand, delayed diagnosis of HIV to late stages who should be offered HIV testing. A systematic review is (CD4 < 350/mm ) leads to worse prognosis for the patient therefore necessary to identify demographic, lifestyle, due to irreversible immunologic damage and associated clinical and laboratory characteristics of patients which problems [13, 15]. might be associated with HIV infection in primary care. Public Health England estimated that out of the 101,200 The identified characteristics will be investigated to deter- individuals living with HIV in 2015, 6095 were newly diag- mine if they are documented in electronic primary care nosed and 13% were unaware of their HIV status [6]. In records and whether they can be used to predict which that year, 39% of people that were newly diagnosed with primary care patients are likely to have HIV infection. HIV in the UK were detected late (CD4 < 350/mm ), which This systematic review identifies, critically evaluates and is an intolerably high proportion [6]. Meanwhile, evidence interprets available evidence related to the demographic, shows that about 33% of patients that are diagnosed with lifestyle, clinical and laboratory characteristics associated HIV in the UK would have seen a general practitioner with HIV/AIDS infection in adults in the developed (GP) within the previous year [9, 16, 17]. One study found world [23, 24]. Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 3 of 15 Methods America (USA and Canada), Australia and New Zealand. This systematic review conforms to the requirements of Studies which include children only are excluded. the Preferred Reporting Items for Systematic Reviews and Meta-analyses (Additional file 1, PRISMA) [25]. The Selection procedure methods were detailed in a published protocol, but a Two reviewers independently selected articles in the first summary is included in this section [26]. The PROSPERO and second screening of articles. The first screening registration number for the protocol is CRD42016042427. checked titles/abstracts to find out if articles addressed the review question and fulfilled the inclusion and exclu- sion criteria (Additional file 3: Appendix II). The second Review question screening was the full article review. Differences between This systematic review systematically identifies and the reviewers were resolved through discussions. summarises evidence on characteristics of HIV-infected adults which could be used in a prediction model for Quality assessment and data extraction early detection of HIV in primary care. Quality assessment was done using a checklist for cohort and case-control studies modified from the Scottish The review question is: Intercollegiate Guidelines Network (SIGN) [29]. A data extraction form was developed to collate data What demographic, lifestyle, clinical and laboratory from selected articles. Tabulation and narrative of the characteristics are associated with HIV infection in adults results were produced, and the tabulation contains aged 18 years and over? description of the articles (the author, publication year, the study design, number of participants, population Population, exposure and outcome under study and outcome). Studies selected included human participants ≥ 18 years. Exposures may be demographic, socio-economic or Results clinical risk factors or characteristics associated with Selection procedure HIV infection. The comparison group is either people A total of 26,819 hits were returned from the database without risk factors or no comparison group. The out- searches and NICE and DH, 6173 duplicates were come is laboratory-confirmed HIV/AIDS infection. removed and 20,646 articles were pre-screened (Fig. 1). The first review resulted in selection of 429 articles Study design using titles/abstracts. A discussion was held to agree on This review considers observational (analytical) studies, the articles selected. The reviewers independently selected comparing groups and produces predictive values or suitable articles using full text and a second discussion likelihood ratios (case-control and cohort, both retro- was held. The reviewers agreed on 17 articles: 11 cohort spective and prospective studies) [27]. and 6 case-control studies. Search strategy Quality of studies Studies are identified via electronic searches of EMBASE All 11 cohort studies were of acceptable standard, but (Ovid), MEDLINE (Ovid), The Cochrane Library (Wiley) only 2 were of high quality, in terms of participant and the unpublished grey literature (SIGLE, Google recruitment, sample size and how they dealt with bias. Scholar and BASE). Additional searches are conducted The other articles were not clear about how they dealt on abstracts or conference proceedings using Web of with confounding factors (Table 1). All 6 case-control Science Conference Proceedings Citation Index (CPCI), studies were of acceptable standard, and half of them Global Index Medicus, guidelines (NICE, DH) and reference were of high quality, in terms of participant recruitment, searching [28]. There were no language restrictions, and all sample size and how they dealt with bias. studies published from year 1995 to April 2016 were included. The search terms used in Ovid MEDLINE Study characteristics (Additional file 2: Appendix I) are adjusted to suit The cohort studies were conducted in the UK (3), searches in other databases. References were searched Ireland (1), Australia (1) and USA (6). The number of and stored using the Refworks referencing programme. participants ranged from 32 to over 20,000 with most studies focusing on patients aged ≥ 18 years. The study Inclusion/exclusion criteria duration ranged from 1 to 5 years, but some of the studies To ensure generalisability to a UK setting, only studies did not state follow-up intervals (Table 1). undertaken in the following developed countries are The case-control studies were conducted in the UK included in this review: Europe (all countries) and North (1), Netherlands (1), the USA (2) and Canada (2). In Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 4 of 15 Fig. 1 PRISMA 2009 flow diagram total, they included 1412 cases and 3423 controls. The significant association with the risk of HIV infection study duration ranged from 1 to 12 years with a 6-month [30, 31]. Two studies showed conflicting evidence on follow-up for most of the studies. the increased risk of HIV infection associated with country of birth; one study from the USA showed that Identified predictors of HIV infection being born in the USA was associated with 1.76 times The predictors of HIV identified were categorised into the risk [30], but a study from Australia showed that demographic and socio-economic, behavioural or life- being born in Australia had a non-significant risk [35]. style, clinical features and comorbidities. Statistically Socio-economic conditions associated with increased risk significant characteristics or those with highest percentages of HIV identified were (i) poverty in urban but not in rural were included. areas (1 study) [37], (ii) annual income under $10,000 having 13 times the risk (1 study) [30], (iii) unemployment (1 study) Demography and socio-economic [30], (iv) housing problems (1 study) [30]and (v)not being The significant demographic characteristics (Table 2) a high school graduate or having low education attainment associated with HIV infection were (i) homosexuals and/or (2 studies); 2.2 times the risk [30, 38]. bisexuals, mainly men who have sex with men (MSM) (5 studies) 1.8 to 2.7 times risk [30–34], (ii) black ethnicity Behavioural characteristics (1 study); 6.8 times risk [30] and (iii) age ranges (3 studies), Behavioural characteristics (Table 3) associated with an mainly between 27 and 40 years with up to 11.5 times the increased risk of HIV infection can be categorised into risk [31, 35, 36]. Two studies revealed that gender had no personal lifestyle, partner lifestyle and effects of life events. Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 5 of 15 Table 1 Data extract and quality assessment summary: cohort and case-control studies Study Design Population, Outcome: duration Study addresses an Participants being Indicate how Main potential How well was the study setting and follow-up appropriate and studied are selected many people confounders done to minimise the risk clearly focused from the same source participated identified and of bias or confounding? question populations accounted for 1. Joore I.K. et al., Case-control study 102 cases and 299 HIV infection: 2002–2012 Yes Yes Yes Cannot say + (2015) [42] controls, Amsterdam, Netherlands 2. Damery S. et al. Case-control study 939 cases and 2576 HIV/AIDS diagnosis: Yes Yes Yes Yes ++ (2013) [17] control, UK Jan 1989–Sept 2010 3. Szerlip M.A. Case-control study Older patients aged Diagnosis of HIV infection: Yes Yes Yes Cannot say + et al. (2005) [39] (retrospective) 55 years and over (53 6 months interval up to cases and 106 controls), 12 months New Orleans, USA 4. Ellerbrock T.V. Case-control study 217 cases 395 controls, HIV diagnosis: 1998–2000 Cannot say Yes Yes Cannot say + (2004) [30] FL, USA 5. Burchell, A.N. Case-control study Gay and bisexual men HIV infection: 1998–2006 Yes Yes Yes Yes ++ (2010) 123 cases and 240 controls, Ontario, Canada 6. Burchell, A. N. Case-control study Adults aged 18 years Diagnosed HIV infection: Yes Yes Yes Yes ++ (2003) [41] and over 80 cases June 1998–Dec 2001 (seroconverts) and 106 controls, Ontario, Canada 7. Hodder, S.L. Cohort study N = 2099 (women aged HIV prevalence and Yes Yes Yes Yes + (2013) [36] (prospective) 18–44 with 1 or more incidence: 2009–2010 with personal or partner risk 6-month follow-up to factors), USA 12 months 8. Moran. J. Cohort study N = 1404 HIV infection: 2008–2011 Yes Cannot say Yes No + (2012) [34] Ireland 9. Desai M. Cohort study N = 328 HIV infection: Yes Cannot say Yes No + (2012) [38] UK Sept 2010–Dec 2011 10. Guy R.J. Cohort study N = 7857 (MSM) Victoria, HIV positivity: Yes Yes Yes Cannot say + (2011) [35] Australia Apr 2006–Jun 2009 11. Krauskopf K. Cohort study N = 643 (HIV-infected HIV infection: Yes Yes Yes Yes ++ (2011) [45] and at-risk men aged 2001–2006 6-month 49 years and older), follow-up Bronx, NY, USA 12. Niyonsenga T Cohort study N = 20,528 (all cases AIDS/HIV incidence: 1998– Yes Cannot say Yes Cannot say + (2013) [37] with HIV/AIDS 2002 diagnosis), FL, USA 13. Ross, J. D. Cohort study N = 8466 (population HIV positive results: Yes Yes (1997) [31] aged 16 and over), Jan 1989–Dec 1993 Lothian and Glasgow region of Scotland Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 6 of 15 Table 1 Data extract and quality assessment summary: cohort and case-control studies (Continued) Study Design Population, Outcome: duration Study addresses an Participants being Indicate how Main potential How well was the study setting and follow-up appropriate and studied are selected many people confounders done to minimise the risk clearly focused from the same source participated identified and of bias or confounding? question populations accounted for 14. Gordon S. M. Cohort study N = 32 (HIV-positive HIV positivity: Yes No Yes No + (1995) [32] patients aged ≥ 60) Jan 1985–July 1992 Atlanta, GA, USA 15. Marder K. Cohort study Intravenous drug users HIV infection: recruited Yes Yes Yes Yes ++ (1995) [44] (prospective) (99 HIV + ve patients 124 1988 and followed up for HIV − ve patients), 3.5 years and 6-month New York City, USA follow-up 16. Hafner J. W. Cohort study N = 344 Albuquerque, HIV diagnosis: 19-month Yes Yes Cannot say + (1997) [33] (retrospective) NM, USA period July 1993–Jan 1995 17. Landau R. Cohort study N = 133 (A&E patients HIV infection: 1991–1994 Yes Yes Yes No + (1997) [43] (retrospective) aware and unaware of HIV status), London, UK Modified from Scottish Intercollegiate Guidelines Network (SIGN) Minimise risk of bias or cofounding: high quality (++) □ acceptable (+) □ unacceptable—reject 0 Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 7 of 15 Table 2 Demographic characteristics identified in selected studies Studies Ellerbrock 2004 [30] Guy 2011 [35] Hodder 2013 [36] Ross 1997 [31] Niyonsenga 2013 [37] Gordon 1995 [32] Desai 2012 [38] Hafner 1997 [33] Moran 2012 [34] OR OR OR OR CC** % % % Demographic Age Reference group < 30 y 18–26 years 21–25 years 26–30 1.7 (1.05–2.8) 27–33 5.83 (1.22–27.96) 30–39 1.91 (1.27-2.87) 31–35 0.3* 34+ 11.54 (2.71–49.05) 36–40 1.6* 40+ 1.81 (1.19-2.75) Ethnicity Black race 6.77 (4.17–11) (Reference = white) Aboriginal or Torres 1.68* (0.41–6.94) Strait Islander Country of Born in USA 1.76 (1.22–2.53) birth Born in Australia 1.42* (1.00–2.02) Sexuality Homosexual/ 1.79* (0.67–4.79) 2.7 (1.5–4.8) 37% 57% 61% bisexual Heterosexual 1.00 1.0 3% 28% Socio-economic factor Housing problems 17% Poverty index in rural areas − 0.25* Poverty index in urban areas 0.58 Annual income < $10,000 13.2 (7.91–22) Farmworker 2.09 (1.47–2.96) Unemployed 5.08 (3.18–8.14) 26% Education beyond high school 0.43* (0.15–1.24) Not a high school graduate 2.15 (1.48–3.1) NB % do not add up to 100% because they are provided for all risk factors *Not statistically significant **Correlation coefficient Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 8 of 15 Table 3 Behavioural or lifestyle––personal choices identified in selected studies Predictor Ellerbrock Gordon Guy 2011 [35] Hafner Hodder Moran Ross Desai Szerlip 2004 [30] 1995 [32] 1997 [33] 2013 [36] 2012 [34] 1997 [31] 2012 [38] 2005 [39] OR % OR % OR % OR % OR Injected drugs users 21.1 (4.89–90.9) 18% 2.97 (1.77–5.00) 30% 2.71 (1.33–5.53) 10% 2.3 (1.5–3.5) Ever smoked crack 22.8 (12.6–41.5) cocaine Binge-drinking or 1.57* (0.74–3.33) 12.8 (1.65–99) alcohol misuse Substance use 2.52 (1.22–5.21) 22% (combined)** Current smokers 25% Unsafe sex 1.84 (1.6– 3.20) 60% HIV positive partner 3.24 (1.47–7.11) Sex with drug user 17.2 (7.18–40.9) Contact abroad 2* Ever exchanged money 19.3 (11.2–33.2) or drugs for sex Male anal sex in the last 1.63 (1.13– 2.35) ≥ 6 months Multiple life partners M: 5.51 (3.18–9.55) F: 19.8 (8.81–44.2) Obesity 10% *Not statistically significant **Includes drug use or binge-drinking Personal lifestyle choices identified were (i) injecting drugs symptoms including fever/chills and cough (3 studies); 4.5 (7 studies); 2 to 21 times the risk [30, 31][32–36], (ii) times the risk [33, 39, 41], (ii) rash (1 study); 4.5 times the smoking crack cocaine (1 study); 22.8 times the risk risk [39], (iii) weight loss (2 studies); 13 to 39 times the [30], (iii) being a current smoker (1 study) [38], (iv) risk [17, 41], (iv) diarrhoea (2 studies); 2 to 4.4 times binge-drinking (1 study); 12.8 times the risk [34], (v) the risk [17, 41] and one study identified abdominal exchanging money or drugs for sex (1 study); 19 times pain, minor trauma and nausea/vomiting as the condition the risk [30], (vi) male anal sex (1 study); 1.6 times the affecting 5–6% of the HIV-positive patients [33]. risk [35] and (vii) being obese (1 study) [30]. Personal sexual behaviours identified were unsafe sex (2 studies); Comorbidities associated with HIV 1.8 times the risk [35, 38] and having multiple sex partners The clinical indicator conditions (Table 4) were categorised (1 study); 5.5 times the risk for males with ≥ 10 and 20 into the following: respiratory, dermatology, neurology, times the risk for females with ≥ 3 lifetime partners [30]. gastroenterology, gynaecology, haematology, ophthalmology, Partner-related behaviours identified were (i) HIV-positive ear, nose and throat (ENT) and other (not classified). partner(2studies); 3and 8times therisk[35, 36], (ii) The respiratory conditions identified were pneumonia partner’s use of illicit drugs (2 studies); 1.57 and 17 times (2 studies); 8 and 48 times the risk [17, 41] and pneumo- [30, 36], (iii) partner’s alcohol dependence/binge-drinking cystis in 52% of the HIV-infected patients (1 study) [42]. (1 study); 1.4 to 1.8 times the risk [39]. The dermatological conditions identified were psoriasis One study revealed risk-associated stressful events in (2 studies); 2.6 to 3 times the risk [17, 41] and herpes men having sex with men to be; (i) the number of stressful zoster (2 studies); 10.9 and 25.4 times the risk [17, 41]. events, (ii) events occur in ages under 30 years associated The evidence revealed that HIV infection was signifi- with 7 times the risk, (iii) type of stressful events such as cantly associated with peripheral neuropathy (1 study); bereavement and death of close friend and financial crisis 15.9 times the risk [41] and neurologic disabilities cranial and relationship breakdown (romantic and other relations); nerve abnormalities and fine limb movement (1 study); 3times therisk [40]. 2.4 times the risk in women and 1.9 times the risk in men [43]. The gastroenterological conditions identified were Clinical features oral candidiasis (2 studies); 7.1 and 29.4 times the risk Evidence from 4 studies (Table 4) revealed that HIV [17, 41], hepatitis B (2 studies); 8.3 and 11.5 times the infection was associated with clinical features: (i) flu-like risk [44, 41] and liver diseases (1 study), affecting 22% Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 9 of 15 Table 4 Clinical features and comorbidities identified in selected studies Condition Damery Joore Hafner Marder Burchell Szerlip Krauskopf Landau Hodder Guy Ellerbrock 2013 [17] 2015 [42] 1997 [33] 1995 [44] 2003 [41] 2005 [39] 2011 [45] 1997 [43] 2013 [36] 2011 [35] 2004 [30] OR (CI) OR (CI) % OR % & OR OR % % OR OR OR Clinical features Weight loss 13.4 39.6 (5.15–6.7) (6.2–∞) Fever or chills 4.5* 13% (0.5–54.3) Cough 7% Flu-like symptoms 76% Diarrhoea 2* (0.2–17.4) Diarrhoea one only 3.7* consultation (0.9–5.48) Diarrhoea two 4.4 consultation (2.3–2.81) Abdominal pain 5% Minor trauma 6% Nausea/vomiting 6% Rash 4.5 Number of HIV One 11.7 indicator conditions (6–23.6) Two 77.5 (18.2–700.8) Comorbidities Respiratory Pneumonia 47.7 8.3 (3.54–52) (2–49.8) Pneumocystis carinii 52% Dermatology Psoriasis 2.9* (0.1–∞) Psoriasis—one 2.6 consultation only (1.69–1.5) Psoriasis—two 3 consultations (1.38–2.5) Herpes zoster 25.4 10.9 (5.76–14.2) (2–108.9) Neurology Peripheral neuropathy 15.9 (2–∞) Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 10 of 15 Table 4 Clinical features and comorbidities identified in selected studies (Continued) Condition Damery Joore Hafner Marder Burchell Szerlip Krauskopf Landau Hodder Guy Ellerbrock 2013 [17] 2015 [42] 1997 [33] 1995 [44] 2003 [41] 2005 [39] 2011 [45] 1997 [43] 2013 [36] 2011 [35] 2004 [30] OR (CI) OR (CI) % OR % & OR OR % % OR OR OR Neurologic disability 2.4 in women Neurologic disability 1.9 in men (1.1–3.2) Gastroenterology Oral candidiasis 29.4 7.1* (4.57–21.8) (0.6–∞) Hepatitis B 11.5 8.3 (1.2–∞) (2.65–26.2) Chronic liver disease 22% (15%–29%) Oncology Non-Hodgkin’s lymphoma 12.6 (2.13–15) Lymphogranuloma venereum 7.1* (0.6–∞) Gynaecology Cervical dysplasia 2.9* (0.4–232.4) Condyloma acuminata 12.1 (1.2–600.9) Haematology Leucocytopenia 11.5 (1.2–∞) Blood dyscrasia 5.7 (2.44–4) ENT Lymphadenopathy 11.3 29.8 (5.15–5.3) (4.4–∞) Parotitis 8.6 (1.68–11) Other Mononucleosis-like illness 6.2 (1.6–29) Pyrexia of unknown origin 7.2 (4.05–3.5) Hyperlipidemia 25% (17%–32%) Hypertension 10% (4%–16%) Diabetes 10% (5%–14%) Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 11 of 15 Table 4 Clinical features and comorbidities identified in selected studies (Continued) Condition Damery Joore Hafner Marder Burchell Szerlip Krauskopf Landau Hodder Guy Ellerbrock 2013 [17] 2015 [42] 1997 [33] 1995 [44] 2003 [41] 2005 [39] 2011 [45] 1997 [43] 2013 [36] 2011 [35] 2004 [30] OR (CI) OR (CI) % OR % & OR OR % % OR OR OR Sexually Transmitted 10.8 10.1 (3.39–30.12) 10.1 Infection (STI) (3.38–7.6) (6.89–14.9) STI diagnosis ≤ 2 years 2.72 (1.77–4.2) ≤ 14 days 3.19 (2.05–4.96) Number of STIs per patient One 14.6 (5.5–45.6) ≥ 2 37.9 (5.6-∞) Syphilis 39.3 7.35 12.7 (5.7–1703.9) (2.52–21.5) (7.28–22.3) Seropositive for syphilis* 7.29 (4.15–12.8) Infectious Syphilis ≤ 2 years 3.86 diagnosis (1.99–7.5) ≤ 14 days 4.9 (2.51–9.56) Chlamydia 11.8 (3–67.5) Chlamydia diagnosis ≤ 2 years 2.31 (1.4–3.81) ≤ 14 days 2.62 (1.56–4.39) Gonorrhoea 15.9 6.51 (2–∞) (4.4–9.65) Genital herpes 2.9* (0.1–∞) *Not statistically significant ∞ Means infinity upper limit Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 12 of 15 Table 5 Predictors identified and availability in electronic primary care records Category of predictor Predictor of HIV infection Likelihood of being recorded in primary care records Sociodemographic Age Present for all patients Gender Present for all patients Social status Inferred from postcode Poverty index Present as deprivation quintile Annual income Inferred from prescription payments, benefits Employment status Likely to be poorly recorded Sexual orientation Require further investigation Not a high school graduate Not present Country of birth Not present Ethnicity Present for some patients Behavioural Smoking status Very likely to be present Drug use Present for some patients Binge-drinking or alcohol misuse Present for some patients Obesity Very likely to be present Contact abroad Might be present Stressful events Present for some patients Unsafe sex Likely not present Ever exchanged money or drugs for sex Likely not present Male anal sex Likely not present Number of lifetime partners Likely not present Partner characteristics Likely not present Clinical and comorbid conditions Weight loss Likely to be present Fever or chills Likely to be present Cough Likely to be present Flu like symptoms Likely to be present Diarrhoea Likely to be present Abdominal pain Likely to be present Minor trauma Likely to be present Nausea/vomiting Likely to be present Rash Likely to be present Pneumonia Likely to be present Pneumocystis carinii Likely to be present Psoriasis Likely to be present Herpes zoster Likely to be present Peripheral neuropathy Likely to be present Neurologic disability Likely to be present Oral candidiasis Likely to be present Hepatitis B Likely to be present Chronic liver disease Likely to be present Non-Hodgkin’s lymphoma Likely to be present Condyloma acuminata Likely to be present Leucocytopenia Likely to be present Blood dyscrasia Likely to be present Lymphadenopathy Likely to be present Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 13 of 15 Table 5 Predictors identified and availability in electronic primary care records (Continued) Category of predictor Predictor of HIV infection Likelihood of being recorded in primary care records Parotitis Likely to be present Mononucleosis-like illness Likely to be present Pyrexia of unknown origin Likely to be present Hyperlipidemia Likely to be present Hypertension Likely to be present Diabetes Likely to be present Sexually transmitted infection Likely to be present Syphilis Likely to be present Chlamydia Likely to be present Gonorrhoea Likely to be present Genital herpes Likely to be present of the HIV-infected patients [45]. One oncological condi- further investigation to assess if they can be reliably tions identified was Non-Hodgkin’s lymphoma (1 study); identified and included in a future clinical prediction 12.6 times the risk [17]. model (Table 5). Only one study identified gynaecological conditions The demographic and socio-economic predictors associated with increased risk of HIV diagnosis and identified and available in primary care records are age, condyloma acuminata; 12.1 times the risk [41]. The two gender and deprivation quintile as a proxy for some of haematological conditions identified in the studies were the socio-economic predictors. Behavioural predictors leukocytopenia (1 study); 11.5 times the risk [41]and identified and available in electronic health records are blood dyscrasia (1 study); 5.7 times the risk [17]. ENT drug use, binge-drinking or alcohol misuse, current conditions identified were lymphadenopathy (2 studies); smokers and obesity. All the clinical features and comorbid 11.3 and 29.8 times the risk [17, 41] and parotitis (1 study); diseases identified are most probably available in electronic 8.6 times the risk [17]. health records (Table 5). The other conditions identified were mononucleosis-like Some of the demographic, socio-economic and behav- illness (1 study); 6.2 times the risk [41], pyrexia of unknown ioural predictors identified in literature, such as ethnicity, origin (1 study); 7.2 times the risk [17]and onestudy which country of birth, income and education levels, might be had 10–25% of the HIV-infected patients with hyperlipid- available in primary care records and therefore require emia, hypertension and diabetes [45]. The other conditions further investigation on completeness. identified were sexually transmitted infections (5 studies), 2.7to37.9times therisk[17, 30, 35, 44, 41], and the Limitations following infections were identified: (i) syphilis (3 studies), This systematic review focused on studies conducted in 3.9 to 39.3 times the risk [30, 44, 41]; (ii) chlamydia (2 developed countries whereas most of the studies on HIV studies), 2.3 to 11.8 times the risk [30, 35]; (iii) gonorrhoea predictors were conducted in developing countries, (2 studies), 6.5 to 15.9 times the risk [30, 41]and (iv) mostly in Africa. Most of the studies conducted on HIV genitalherpes(1study), 2.9times therisk[41]. were case studies, qualitative studies and cross-sectional studies which are not suitable in identifying risk factors. Some of the studies identified in this systematic review Discussion reported percentages rather than odds ratio in their results This systematic review identified 10 demographic and making the interpretation of risk association difficult. socio-economic characteristics, 11 behavioural character- istics, and 27 clinical features and comorbid conditions Conclusion that are significantly associated with HIV infection. This systematic review revealed existing scientific evidence The purpose of this systematic review was to identify on predictors of HIV that can be used to inform decision predictors of HIV infection available in electronic patient making in prognostic model development [46]. Only 2 records that could be incorporated in a prediction model to demographic and socio-economic characteristics (age and identify primary care patients with undiagnosed HIV. gender) and 4 behavioural characteristics (drugs use, Candidate predictors identified are either routinely re- binge-drinking or alcohol misuse, current smokers and corded in electronic primary care records or require obesity) identified in literature are available in electronic Rumbwere Dube et al. Systematic Reviews (2018) 7:82 Page 14 of 15 primary-care records. The other 8 demographic and Received: 3 January 2018 Accepted: 11 May 2018 socio-economic and 7 behavioural characteristics require further investigation on completeness or if they are not References available at all. Further exploration will determine whether 1. Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb the characteristics can be applied in a model. 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Journal

Systematic ReviewsSpringer Journals

Published: Jun 2, 2018

References

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