HIV Prevalence and Morbidity in Older Inpatients in a High HIV Prevalence Setting

Abstract

Understanding of the burden of HIV infection and comorbid conditions in older adults is limited, especially in low- and middle-income countries. Antiretroviral therapy (ART) has increased longevity of HIV-positive individuals, making age-related comorbidities more likely. This study aimed to compare the demographic and disease profiles, including chronic comorbid conditions of inpatients, at least 50 years of age, by HIV status, admitted to a regional hospital in South Africa. Adults, 50 years of age and older, admitted to internal medicine wards from November 2015 to February 2016 were approached to participate. Sociodemographic data, laboratory results, anthropometric data, discharge diagnoses, and HIV status were collected and compared by HIV serostatus. Overall, 151 participants were enrolled. Their median age was 61 years (IQR: 56–68 years); 89 (58.9%) were women. Overall, 47 (31.1%) were HIV positive, of whom 10 (6.6%) were first diagnosed during the admission. HIV-positive inpatients were younger than HIV-negative patients. The leading discharge diagnoses of all participants were acute gastroenteritis (11.5%) and community-acquired pneumonia (11.5%). Hypertension and type 2 diabetes mellitus (T2DM) were the leading comorbidities in both HIV-negative and HIV-positive participants. Prevalence of hypertension was 75.0% in seronegative, 59.5% in those with a prior diagnosis of HIV, and 40.0% in newly diagnosed; similarly, prevalence of T2DM was 22.1% in HIV-negative and 24.3% in known HIV-positive participants. Similar proportions died during admission; 11.3% of HIV-negative and 12.7% of HIV-positive admitted inpatients died. Almost one third of patients admitted were HIV positive. In HIV-positive older admitted to hospital, the leading cause for hospitalization was coinfections. In the ART era, irrespective of HIV status, older patients have similar age-related chronic illnesses and similar mortality rates, despite younger age at admission.

Introduction

Antiretroviral treatment (ART) has had an immediate and dramatic improvement in prognosis, quality of life, and longevity of HIV-positive individuals. This, together with the introduction of universal test and treat strategies for HIV, has led to an increase in the number of adults, 50 years and older, diagnosed with HIV infection.¹ Indeed, it is estimated that there are 32 million adults 50 years and older globally, of whom 13% are HIV positive, representing 3.6 million people.² The majority (2.9 million) live in middle- and low-income countries, where they represent 10% of the population.² Moreover, an estimated 100,000 adults, 50 years of age and older, acquire HIV infection every year in low- and middle-income countries, 74% of who live in sub-Saharan Africa.² More than 2 million people 50 years of age and older living in sub-Saharan Africa are HIV positive, accounting for 60% of all people living with HIV, older than 50 years, globally.³

Due to the complex interaction between HIV, ART, and inflammatory and pathological disease processes, the disease and comorbidity profile of older HIV-positive individuals are changing. Aging is associated with physiological changes, including reduction in glomerular filtration rate, hardening of vessels, immunosenescence, and neurodegeneration. As a result, older individuals are more prone to both infectious and noncommunicable diseases. The prevalence of chronic disorders increases with age, with 30% of the people 50 years of age and older in South Africa having two or more chronic comordities,⁴ resulting a high proportion receiving treatment for chronic disorders.^5,6 In South Africa alone, the estimated number of people 50 years of age and older receiving ART is 753,000.⁷ Aging populations increase health utilization, and the age profile of patients with severe illness has implications not only for individuals and their quality of life but also for health services.⁴

This study determined the HIV prevalence, demographics, and disease profile of patients 50 years of age and older, admitted to the adult medical wards at Tshepong Hospital.

Research Methods and Design

Study design, setting, and population

We conducted a cross-sectional study of inpatients 50 years of age and older, admitted to the medical wards at Tshepong Hospital in Matlosana, South Africa, from November 2015 to February 2016. Klerksdorp/Tshepong Hospital Complex is a secondary level hospital in the North West Province, offering a range of specialist services. The Internal Medicine Department is located at Tshepong Hospital and operates an adult medical admission ward and five adult internal medicine wards, each of which can accommodate 36 patients. Approximately 600 patients are admitted per month to the adult internal medicine wards, of whom 240 (40%) are 50 years of age and older.

Participants were recruited on admission and followed up prospectively until they were discharge demised inhospital. All patients 50 years of age and older, admitted to adult medical wards with acute medical illnesses from the emergency department, outpatient departments, or referral hospitals/clinics on Sundays, Mondays, and Thursdays during the study period, were approached to participate in the study. These days were selected to ensure that the sample population would be representative of patients admitted on weekdays and weekends. Patients were excluded when informed consent could not be obtained or HIV testing declined. We abstracted daily tallies of all potentially eligible patients for the duration of the study from the ward admission register.

Information regarding patient's age, gender, source of income, housing, and primary caregiver was collected during a patient interview, comorbid conditions (for the purpose of this study were defined as either newly diagnosed at enrolment, or diagnosed before study enrolment), HIV status and if HIV positive, participants were categorized as either known or newly diagnosed with HIV. Tobacco and/or alcohol use was captured. For study participants who were HIV positive, their most recent CD4 cell count and viral load results were obtained from participants' medical records or electronic laboratory results, provided they were not taken more than 6 months before the date of admission. If the CD4 cell count and viral load were taken more than 6 months ago, new samples were taken as per national guidelines.⁸ Those who reported being HIV seronegative or not knowing their HIV status had a routine rapid HIV test done. As per South African guidelines, those testing positive had a confirmatory rapid test performed using a different manufacturer's HIV test.⁸ In South Africa, a specimen for CD4 cell count is routinely taken for all newly diagnosed HIV-infected individuals.⁸ Anthropometric data recorded included weight, height, hip circumference, and waist circumference. Body mass index (BMI) was calculated using weight and height measured on participants able to stand, using a digital calibrated scale and stadiometer, as no bed weighing scales were available. Admission hemoglobin and creatinine concentration, outcome of hospital stay (discharged or in-hospital death), and outcome diagnoses at discharge or death (categorized according to ICD-10 Version: 2016) were abstracted from clinical records.

We defined discharge diagnosis as diagnoses listed on patients' discharge summaries, determined by the treating physician. In those participants who died, the most likely cause of death was determined by death report forms completed at daily mortality meetings. Medical conditions were considered comorbid if patients reported that they were taking or told that they required long-term medical treatment for an illness/illnesses.

Data analysis

Data were captured from patient interviews, abstracted from patient records and laboratory resulting system, and entered into a study RedCap™ database, after review and validation by a study physician.

We anticipated based on prior admission records that, over the study period, approximately admitted 600 patients could be eligible for recruitment to the study. However, we recruited patients admitted 3 days a week, giving us an estimated 250 potentially eligible individuals for recruitment. Frequencies and percentages were calculated for categorical variables, whereas median and interquartile range (IQR) were determined for continuous variables, where pertinent, patient characteristics were stratified by HIV status and gender. The Kruskal-Wallis test was used to compare the continuous variables and p-values were obtained. Variables with p-value ≤.05 were considered significant. Analysis was conducted using SAS Enterprise Guide 7.1.

Ethical Considerations

Ethical clearance was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand (clearance certificate number: M150739). Permission to conduct research was obtained from the Klerksdorp/Tshepong Hospital Complex and the North West Provincial Department of Health.

Results

Using admission data for the hospital, we estimate that a total of 1,197 patients, 50 years of age and older, were admitted during the study period, of whom 478 (39.9%) were admitted on Sundays, Mondays, and Thursdays. We approached a total of 277 patients and enrolled 151 patients (an estimated 31% of all eligible admissions; and 40% of admissions on recruitment days over the study period). Patients not enrolled either declined consent for study participation and/or HIV testing (103/277; 37.2%) or were unable to provide consent due to their medical illness (23/277; 8.30%) (delirium, dementia, or cerebrovascular accident).

A large proportion (47/151; 31.1%) were HIV positive, of whom 37 (78.7%) self-reported they were previously diagnosed with HIV and 10 (21.3%) were newly diagnosed at the current admission. The median age of recruited patients was 61 years (IQR: 56–68 years). HIV-positive participants were younger (median age of 57 years; IQR: 53–62) than HIV-negative participants (median 64.27; IQR: 57–71) (p-value<.0001). Overall, 89 participants (58.9%) were women. Of the 47 HIV-positive participants, 28 (59.6%) were women. The median age of women HIV-positive participants was 57 years (IQR: 54–62), and that of men was 56 years (IQR: 53–60) (Table 1).

Table 1.

Baseline Characteristics of Admitted Patients Older Than 50 Years Stratified by HIV Status (n = 151)

	Overall	HIV positive	HIV negative	p-value
Number	151	47	104
Age (years)
Median (IQR)	61 (56–68)	57 (53–62)	64 (57–71)	<.0001
Age by groups (n)
50–54	35	17	18
55–59	33	12	21
60–64	29	11	18
65–69	20	4	16
70–74	18	3	15
>75	16	0	16
Gender
Female (%)	89 (58.9%)	28 (59.6%)	61 (58.6%)
Creatinine (μmol/L)	n = 148	n = 46	n = 102
Median (IQR)	87 (72–132)	100.5 (65–166)	86.5 (73–119)	.2435
Hemoglobin (g/dL)	n = 150	n = 47	n = 103
Median (IQR)	12.35 (10.4–13.9)	11.6 (9.2–13)	12.8 (10.6–14.5)	.0056
Hospitalization outcome	n = 149	n = 47	n = 102
Death (%)	18 (12.08)	6 (12.77)	12 (11.76)
Discharge (%)	131 (87.92)	41 (87.23)	90 (88.24)

BMI was calculated on admission in patients who were able to stand and have their weight and height measured, (85/151; 56.3%). BMI was lower among HIV-positive participants, particularly those who were newly diagnosed with HIV. Similarly, waist circumference was obtained from 85 patients (64 HIV-negative participants, 16 participants known HIV positive, and 5 newly diagnosed HIV positive). The median waist circumference among all participants was 88.00 cm (IQR: 79.0–102.0). Among the known HIV-positive participants, the median was 83.0cm (IQR: 73.0–96.3); newly diagnosed HIV-positive participants had a median waist circumference of 79.0 cm (IQR: 78.0–84.0); and in the HIV-negative group, the median was 90.0 cm (IQR: 79.8–105.3).

The median hemoglobin was 12.4 g/dL (IQR: 10.4–13.9). The lowest values were among the newly diagnosed HIV-positive participants (median value in this group was 11.4 g/dL). The difference in median hemoglobin between the HIV-positive and HIV-negative participants was statistically significant (p-value .006). Median creatinine was 87.0 μmol/L (IQR: 72.0–132.0) and highest among the known HIV-positive participants (median creatinine 101.5 μmol/L; IQR: 76.5–157.0). The difference in creatinine between the HIV-positive and HIV-negative participants was not statistically significant (p-value = .244) (Table 1).

Overall, 18 participants (11.9%) died in hospital and 2 (1.3%) were lost to follow-up, their discharge summaries and death reports were not traceable. Mortality was similar by HIV status—11.5% (12/104) in HIV-negative participants and 12.7% (6/47) in HIV-positive participants.

Twenty-five (16.9%) of the participants felt they would require a caregiver on discharge to assist with eating (64.0%), bathing (76.0%), and using the toilet (96.0%). Most (78.8%) study participants were reliant on immediate or extended family for care, with only 17.2% independently caring for themselves. A large proportion (59.6%) of study participants received social grants as their sole source of income; 22 (15.1%) of study participants were working and 13.0% received a pension. Most self-reported living in brick and mortar housing (80.8%); only one participant reported living in an assisted care facility.

HIV infection

Participants newly diagnosed with HIV (10/47) had a lower CD4 cell count (209 cells/μL; IQR: 120.0–379.0) than those previously diagnosed with HIV (255.5 cells/μL; IQR: 102.0–470.5). Most HIV-positive adults (33/37; 89.2%) had been initiated on ART before their admission, for a median duration of 2.6 years; two participants were on ART for less than 6 months, five participants for 6–12 months, and 25 participants for more than 1 year. The duration on ART could not be determined for one patient. Three participants had not yet initiated ART and one had defaulted previously. The leading ART regimen received by participants was tenofovir-emtricitabine-efavirenz fixed-dose combination (84.8%), with only 3 (9.1%) on a protease inhibitor-containing regimen. Fourteen of 29 (48.3%) participants in whom a viral load was available were virally suppressed (viral load of <20 copies/mL), with the majority (11) on ART for more than a year (Table 2).

Table 2.

Characteristics of Known HIV-Positive Study Participants (n = 37)

	Overall	Males	Females
Number	37	15	22
Median age (years) (IQR)	57 (53–62)	56 (53–61)	57 (53.3–62.8)
Number on ARV (%)	33 (89.2%)	13 (86.7%)	20 (90.9%)
Duration on ARV
Less than 6 months	2	0	2
6–12 months	5	3	2
More than 1 year	25	10	15
Unknown	1	0	1
Median CD4 cell count (cells/μL) (IQR)	255.5 (102.0–470.5)	247.0 (126.0–473.0)	264.0 (72.0–451.0)
Virally suppressed^* (Viral load <20 copies/mL)	14/29 (48.3%)	4/10 (40.0%)	10/19 (52.6%)
Viral load (copies/mL)^*
<50 (%)	16 (55.2%)	5 (50%)	11 (57.9%)
50–1000 (%)	2 (6.9%)	1 (10%)	1 (5.3%)
>1000 (%)	11 (37.9%)	4 (40%)	7 (36.8%)

From viral loads available on 29 participants.

Comorbid conditions

Overall, hypertension was the leading comorbid condition (68.9%), followed by type 2 diabetes mellitus (21.2%) and chronic obstructive pulmonary disease (COPD) (13.9%). Other comorbid conditions included chronic cardiac disease: atrial fibrillation, valvular heart disease (5.3%), epilepsy (5.3%), cerebrovascular accident (4.0%), and thyroid disorders (3.3%). The comorbid profile among the three HIV status groups showed a similar distribution (Table 3).

Table 3.

Common Comorbid Condition Patients 50 Years of Age and Older Stratified by HIV Status as a Percentage

Comorbid condition	Overall (n = 151)	HIV positive (n = 47)	HIV negative (n = 104)
Hypertension	68.9%	55.3%	75.0%
Type II diabetes mellitus	21.2%	19.1%	22.1%
COPD	14.0%	10.6%	15.4%
Epilepsy	5.3%	4.3%	5.8%
Cardiac disease	5.3%	2.1%	6.7%
Cerebrovascular accident	4.0%	2.1%	4.8%
Thyroid disease	3.3%	2.1%	3.9%

Of patients with COPD, 17 reported prior (58.8%) or current (41.2%) tobacco smoking, with 12 (70.6%) having a pack-year history of greater than 10. Five COPD patients were HIV positive, none had a smoking pack-year history of greater than 10.

Twenty-nine participants had comorbid hypertension and diabetes (19.2% of all participants). Of those, 8 were known HIV positive and the remainder HIV negative.

Discharge/death diagnoses

The leading discharge diagnosis among all participants was acute gastroenteritis (AGE) and community-acquired pneumonia (both 11.5%). of whom 5 (3.3%) and 2 (1.3%) patients had acute renal dysfunction. respectively. Acute exacerbation of chronic obstructive pulmonary disease (COPD AE) (9.9%), uncontrolled hypertension (9.2%), and congestive cardiac failure (7.6%) was the next most common diagnoses. Hyperglycemia accounted for 5.3% of admissions (7 participants), with 2 being admitted with hyperglycemic emergencies. Cerebrovascular events (transient ischemic attacks and cerebrovascular accidents) and cor pulmonale accounted for 4.6% of admissions. Table 4 shows the distribution of admissions stratified by HIV status.

Table 4.

Discharge Diagnoses of Patients 50 Years of Age and Older Stratified by HIV Status as a Percentage

Diagnosis	Overall (n = 131)	HIV positive (n = 41)	HIV negative (n = 90)
Acute gastroenteritis	11.5%	14.6%	10.0%
Community-Acquired Pneumonia	11.5%	7.3%	13.3%
Uncontrolled hypertension	9.2%	2.4%	12.2%
Acute exacerbation COPD	9.9%	7.3%	11.1%
Congestive cardiac failure	7.6%	7.3%	7.8%
Urinary tract infection	6.1%	12.2%	3.3%
Cor Pulmonale	4.6%	2.4%	5.6%
Hyperglycemia	5.3%	2.4%	6.7%
Cerebrovascular event	4.6%	4.9%	4.4%

COPD, chronic obstructive pulmonary disease.

Eighteen participants (11.9%) died in hospital, 12 (7.9%) were HIV negative, and six (4.0%) HIV positive, of whom one (0.7%) was newly diagnosed with HIV with a CD4 cell count of 10.0 cells/μL. In the five patients who died with known HIV infection, their median CD4 count was 106 cells/μL (IQR 26.0–137.0) and the median viral load (available for 4/5 patients) was 148 085.5 copies/mL (IQR 16.50–1 384 646.50). Two of the five were virally suppressed. In the HIV-positive participants, the likely causes of death were intra-abdominal malignancy (1 patient), AGE (2 patients, of whom 1 had renal dysfunction), pneumocystis pneumonia (1 patient), community-acquired pneumonia with associated renal dysfunction (1 patient), and Steven-Johnson's syndrome (1 patient). There was a wide range in the duration on ART and CD4 cell counts in those who died. In the HIV-negative group, the common causes of death were AGE (2 patients of whom 1 had renal dysfunction), congestive cardiac failure (3 patients), tuberculosis (2 patients), and acute exacerbation of COPD (1 patient).

One hundred and one (69.6%) participants had a urine dipstick done on admission; 18.8% had evidence of proteinuria and 22.8% glycosuria. All three HIV-positive patients with proteinuria had comorbid hypertension. Eight HIV-positive patients had glycosuria, of whom only four were diabetic. There was no statistically significant difference in the creatinine of HIV-positive participants when comparing those on ART to those not on ART (p-value = .7245).

Tuberculosis (TB) was diagnosed in six participants, of whom three (50%) were HIV positive. Three patients had drug-sensitive TB (two were HIV negative) and three had multidrug-resistant TB (MDR-TB). One patient with MDR-TB and one patient with drug-sensitive TB demised; both were HIV negative.

Table 5 reports the number of AIDS defining and associated conditions diagnosed in the HIV-positive participants.

Table 5.

WHO AIDS Defining and Associated Conditions Among HIV-Positive Patients (n = 47)

	Discharged (n = 41)	Demised (n = 6)
Tuberculosis	3	—
Herpes Zoster	1	—
Molluscum Contagiosum	1	—
Oral Candidiasis	—	1
Pneumocystis jiroveci pneumonia	—	1
Acute gastroenteritis	6	2
Community-Acquired Pneumonia	3	1

Discussion

In this study of admitted patients older than 50 years, almost one third of patients admitted to internal medicine wards were HIV positive. In HIV-positive patients, the leading diagnoses at discharge were coinfections. Worryingly, for the achievement of 90-90-90 goals,⁹ less than half of the HIV-positive participants receiving ART were virally suppressed.

Noninfectious comorbidities (hypertension and diabetes) were common in both HIV-positive and HIV-negative participants. Similar to other studies, chronic comorbidities are common in HIV-positive individuals.^3,10,11 HIV may be coincidental and can be an additional risk factor for cardiovascular disease and malignancy, or may contribute directly to diagnosis.^12,13 Given this association, older patients diagnosed with these diseases should be offered HIV testing.

An interesting finding was the marked age difference between the HIV-negative HIV-positive group lending credence to accelerated aging and progression of chronic diseases in HIV infection and ART.¹² This finding may suggest that screening for comorbid illness should be conducted at a younger age in HIV-positive individuals, to start treatment earlier in the disease process.

The absolute and relative increase in the number of people living with HIV 50 years of age and older are due to three main factors: the success of ART in prolonging the lives of HIV-positive individuals; the reducing incidence of HIV in younger individuals, which shifts the burden of disease; and people 50 years of age and older sharing risk factors with younger people for acquisition of HIV infection.² Casual sex has been reported in individuals 80 years of age and older,¹⁴ yet there is less knowledge and use of condoms.^3,14 Moreover, thinning of mucosal surfaces with age and after menopause may increase risk of acquiring HIV.³ Greater efforts should be made to target HIV prevention programs in this vulnerable population.

Increased life expectancy of HIV-positive individuals may result in the unmasking of the burden of noncommunicable diseases, previously hidden due to the high mortality among younger HIV-positive individuals. Due to frequent interactions with health care facilities and practitioners, while receiving ART, combined with guidelines for routine examination and investigations, HIV-positive patients are more likely to have comorbid diseases detected earlier.^8,15

Comorbid hypertension, and type 2 diabetes mellitus with raised abdominal circumference fulfill criteria for Metabolic Syndrome, which we report in 17/85 (20%) study participants in whom an abdominal circumference could be measured The Metabolic Syndrome increases the risk for cardiovascular disease.¹⁶ This reinforces the need for adequate lifestyle modification programs for HIV-positive individuals, as well as earlier screening for metabolic diseases in this population.

Renal disease was more severe or more prevalent in the older HIV-positive participants in our study. Tenofovir, AGE, CAP, diabetes, and hypertension^17,18 likely contributed to renal injury. The presence of glycosuria in HIV-positive patients in the absence of diabetes suggests the possibility of tenofovir-induced tubulopathy,^19

–23 while proteinuria in the absence of other comorbidities in the newly diagnosed HIV-positive patients may be suggestive of HIV-associated nephropathy.^24

–28

Emphysematous lung disease is more common in HIV-positive individuals even after adjusting for smoking,^29

–32 a risk that persists even after virological suppression.^30,33 Smoking prevalence among HIV-positive individuals is higher than in their HIV-negative peers³⁴; hence, smoking cessation should be encouraged in HIV-positive individuals.

There are limited literature comparing discharged diagnoses of HIV-positive and HIV-negative patients, but a study conducted in Canada looking at the use of acute health services by patients 50 years of age and older found diseases of the respiratory, circulatory, and digestive system among its' top 5 diagnostic categories—similar to our study.³⁵ A cross-section of HIV-positive patients in Brazil had a study population, where 15.7% of the patients were 50 years of age and older, and found that after opportunistic infections, community-acquired pneumonia and gastrointestinal infections were the most common causes of hospitalization.³⁶

Few studies from high HIV burden settings have reported on the burden of disease in older inpatients, but it is becoming increasingly important, as HIV-positive adults age,^{2,6,37

–43} to understand the dynamics and challenges associated with treating this group of patients

Limitations

This was a single-center study with a small sample size, recruited over a short period. Seasonal differences could therefore have been missed. Incomplete record keeping of potentially eligible admission ensured that an accurate assessment of the total number of eligible study participants was not available. Similarly, laboratory results relied on routinely collected data, which were not always available. We were unable to obtain anthropometric measurements on all study participants. Our estimates of mortality in the groups are likely an underestimate, affected by misclassification bias as those not able to provide consent were excluded the study.

Conclusion

Older patients have similar age-related noninfectious chronic illnesses and causes for hospitalization, irrespective of HIV status. Noninfectious chronic illnesses occurred at an earlier age in HIV-positive participants, and screening for these conditions should be considered earlier in HIV-positive individuals. Older patients are also at risk for acquiring HIV. Therefore, HIV prevention and screening programs should also be targeted at older age groups.

Footnotes

Acknowledgment

To all the study participants, staff at Tshepong Hospital, and staff at PHRU.

Authorship Contributions

V.A.N. was the project leader and primary author. N.A.M. and E.V. assisted with study conception and design, and editing of the article. K.M. and W.J. assisted with data acquisition. P.A. and K.O. assisted with analysis and interpretation of data.

Disclaimer

The views expressed in this article are that of the author(s) and not an official position of the North West Department of Health, Tshepong Hospital, PHRU, SA MRC, or the University of the Witwatersrand.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

The South African Medical Research Council funded research costs. Patient care was provided by the North West Department of Health.

References

UNAIDS: UNAIDS Data 2018. Available at www.unaids.org/sites/default/files/media_asset/unaids-data-2018_en.pdf, accessed May 26, 2019 .

UNAIDS: HIV and aging: A special supplement to the UNAIDS report on the global AIDS epidemic 2013. Available at www.unaids.org/sites/default/files/media_asset/20131101_JC2563_hiv-and-aging_en_0.pdf. Published 2013, accessed March 13, 2017 .

Hontelez

JAC

, de Vlas

, Baltussen

, et al.: The impact of antiretroviral treatment on the age composition of the HIV epidemic in sub-Saharan Africa. AIDS, 2012; 26 Suppl 1:S19–S30.

Negin

, Martiniuk

, Cumming

, et al.: Prevalence of HIV and chronic comorbidities among older adults. AIDS, 2012; 26:S55–S63.

Claxton

, Cramer

, Pierce

: A systematic review of the associations between dose regimens and medication compliance. Clin Ther, 2001; 23:1296–1310.

van Eijken

, Tsang

, Wensing

, de Smet

PAGM

, Grol

RPTM

: Interventions to improve medication compliance in older patients living in the community: A systematic review of the literature. Drugs Aging, 2003; 20:229–240.

Simbayi LC, Zuma K, Zungu N, et al.: South African national HIV prevalence, incidence and behaviour survey, 2017. Available at www.hsrc.ac.za/uploads/pageContent/9234/FINAL%20Presentation%20for%2017%20July%20launch.pdf. Published July, 2018, accessed September 4, 2018.

Meintjes G, Moorhouse MA, Carmona S, et al.: Adult antiretroviral therapy guidelines 2017. South African J HIV Med 2017;18:.DO - 104102/sajhivmed.v18i1776. July 2017. Available at https://sajhivmed.org.za/index.php/hivmed/article/view/776/969, accessed November 2, 2017.

UNAIDS: 90-90-90: An ambitious treatment target to help end the AIDS epidemic. Available at www.unaids.org/sites/default/files/media_asset/90-90-90_en.pdf, accessed June 15, 2019 .

10.

Mtei

, Pallangyo

: HIV infection in elderly medical patients. East Afr Med J, 2001; 78:144–147.

11.

Orlando

, Meraviglia

, Cordier

, et al.: Antiretroviral treatment and age-related comorbidities in a cohort of older HIV-infected patients. HIV Med, 2006; 7:549–557.

12.

Onen

, Overton

: A review of premature frailty in HIV-infected persons; another manifestation of HIV-related accelerated aging. Curr Aging Sci, 2011; 4:33–41.

13.

Aberg

: Aging, inflammation, and HIV infection. Top Antivir Med, 2012; 20:101–105.

14.

Rosenberg

, Gomez-Olive

, Rohr

, et al.: Sexual behaviors and HIV status: A population-based study among older adults in rural South Africa. J Acquir Immune Defic Syndr, 2017; 74:e9–e17.

15.

Aberg

, Gallant

, Ghanem

, Emmanuel

, Zingman

, Horberg

: Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis, 2014; 58:e1–e34.

16.

Alberti

KGMM

, Eckel

, Grundy

, et al.: Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation, 2009; 120:1640–1645.

17.

Hirschhorn

, Kaaya

, Garrity

, Chopyak

, Fawzi

MCS

: Cancer and the “other” noncommunicable chronic diseases in older people living with HIV/AIDS in resource-limited settings: A challenge to success. AIDS, 2012; 26 Suppl 1:S65–S75.

18.

Seedat

, Martinson

, Motlhaoleng

, et al.: Acute Kidney Injury, Risk Factors, and Prognosis in Hospitalized HIV-Infected Adults in South Africa, Compared by Tenofovir Exposure. AIDS Res Hum Retroviruses, 2017; 33:33–40.

19.

Gupta

: Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS, 2008; 22:99–103.

20.

Perazella

: Tenofovir-induced kidney disease: An acquired renal tubular mitochondriopathy. Kidney Int, 2010; 78:1060–1063.

21.

Peyriere

, Reynes

, Rouanet

, et al.: Renal tubular dysfunction associated with tenofovir therapy: Report of 7 cases. J Acquir Immune Defic Syndr, 2004; 35:269–273.

22.

Irizarry-Alvarado

, Dwyer

, Brumble

, Alvarez

, Mendez

: Proximal tubular dysfunction associated with tenofovir and didanosine causing Fanconi syndrome and diabetes insipidus: A report of 3 cases. AIDS Read, 2009; 19:114–121.

23.

Fernandez-Fernandez

, Montoya-Ferrer

, Sanz

, et al.: Tenofovir Nephrotoxicity: 2011 Update. AIDS Res Treat, 2011; 2011:354908.

24.

Antonello

, Antonello

ICF

, Herrmann

, Tovo

: Proteinuria is common among HIV patients: What are we missing?. Clinics (Sao Paulo), 2015; 70:691–695.

25.

D'Agati

, Appel

: HIV infection and the kidney. J Am Soc Nephrol, 1997; 8:138–152.

26.

Han

, Naicker

, Ramdial

, Assounga

: A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa. Kidney Int, 2006; 69:2243–2250.

27.

Herman

, Klotman

: HIV-associated nephropathy: Epidemiology, pathogenesis, and treatment. Semin Nephrol, 2003; 23:200–208.

28.

Monahan

, Tanji

, Klotman

: HIV-associated nephropathy: An urban epidemic. Semin Nephrol, 2001; 21:394–402.

29.

Diaz

, King

, Pacht

, et al.: Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers. Ann Intern Med, 2000; 132:369–372.

30.

Petrache

, Diab

, Knox

, et al.: HIV associated pulmonary emphysema: A review of the literature and inquiry into its mechanism. Thorax, 2008; 63:463–469.

31.

Guaraldi

, Besutti

, Scaglioni

, et al.: The burden of image based emphysema and bronchiolitis in HIV-infected individuals on antiretroviral therapy. PLoS One, 2014; 9:e109027.

32.

Samperiz

, Guerrero

, Lopez

, et al.: Prevalence of and risk factors for pulmonary abnormalities in HIV-infected patients treated with antiretroviral therapy. HIV Med, 2014; 15:321–329.

33.

Grumelli

, Corry

, Song

L-Z

, et al.: An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Med, 2004; 1:e8.

34.

Elf

, Variava

, Chon

, et al.: Prevalence and Correlates of Smoking Among People Living With HIV in South Africa. Nicotine Tob Res, 2018; 20:1124–1131.

35.

Rotermann

: High use of acute care hospital services at age 50 or older. Heal Rep, 2017; 28:3–16.

36.

Nunes

, Caliani

, Nunes

, Silva

AS da

, Mello

LM de

: Análise do perfil de pacientes com HIV/Aids hospitalizados após introdução da terapia antirretroviral (HAART). Ciênc. Saúde Coletiva, 2015; 20:3191–3198.

37.

World Health Organisation: Global report: UNAIDS report on the global AIDS epidemic 2010. Available at http://files.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2010/20101123_globalreport_en%5B1%5D.pdf. Published November 23, 2010, accessed October 15, 2017 .

38.

Mills

, Bakanda

, Birungi

, et al.: Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: A cohort analysis from Uganda. Ann Intern Med, 2011; 155:209–216.

39.

Gomez-Olive

, Angotti

, Houle

, et al.: Prevalence of HIV among those 15 and older in rural South Africa. AIDS Care, 2013; 25:1122–1128.

40.

May

, Boulle

, Phiri

, et al.: Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: A collaborative analysis of scale-up programmes. Lancet (London, England), 2010; 376:449–457.

41.

Shisana O, Rehle T, Simbayi LC, et al.: South African National HIV Prevalence, Incidence and Behaviour Survey, 2012. Available at www.hsrc.ac.za/uploads/pageContent/4565/SABSSM%20IV%20LEO%20final.pdf. Published 2014, accessed February 23, 2015.

42.

HIV Leadership through Accountability Programme: GNP+. The people living with HIV stigma index, Cameron, October 2012. Available at www.stigmaindex.org/sites/default/files/reports/Cameroon%20People%20Living%20with%20HIV%20StigmaIndex%20Report%20english.pdf. Published 2013, accessed October 19, 2017.

43.

South African National Aids Council: The People Living With HIV Stigma Index: South Africa 2014: Summary Report. Available at www.stigmaindex.org/sites/default/files/reports/Summary-Booklet-on-Stigma-Index-Survey%20South%20Africa.pdf. Published May 2015, accessed October 22, 2017 .