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Achieving the fourth 90: healthy aging for people living with HIV

Harris, Tiffany G.; Rabkin, Miriam; El-Sadr, Wafaa M.

doi: 10.1097/QAD.0000000000001870
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ICAP at Columbia University, Mailman School of Public Health, New York, New York, USA.

Correspondence to Tiffany G. Harris, PhD, MS, Director of Strategic Information, ICAP at Columbia University, Associate Professor of Epidemiology at CUMC, 722 W 168th Street, MSPH Box 18, New York, NY 10032, USA. E-mail: th2604@columbia.edu

Received 15 December, 2017

Revised 17 April, 2018

Accepted 4 May, 2018

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

The availability of potent antiretroviral therapy (ART) has transformed the HIV epidemic, changing HIV disease from a fatal illness to a chronic, manageable condition. In higher income countries, life expectancy for people living with HIV (PLWH) has increased substantially, nearing that of the general population [1–7], and similar gains have been seen in some parts of sub-Saharan Africa, the area of the world most impacted by HIV [2,4,8–12]. Although access to ART is far from universal, substantial progress has been made in reaching the UNAIDS 90–90–90 targets, that is, that 90% of all PLWH in a community or a country are aware of their status, 90% of those aware have initiated ART, and 90% of those on ART achieve durable viral suppression. [13,14]. The median age of PLWH is expected to increase as the scale-up of HIV treatment continues, with more and more PLWH garnering the survival benefits from treatment. Older adults are also at risk of HIV acquisition and they are rarely prioritized for HIV prevention or testing efforts. The resultant ‘greying of the HIV epidemic’ raises important questions regarding understanding the effect of aging on PLWH, the effect of HIV infection on the aging process, and optimal approaches to HIV prevention among older individuals (Table 1). Thus, a critical priority is to aim for healthy aging among PLWH, an achievement that some have called ‘the 4th 90’.

Table 1

Table 1

There is a growing body of work focused on HIV and aging; however, only a minority is from the low and middle-income countries (LMIC) that have the highest burden of HIV. In this article, we provide an overview of HIV among older PLWH and highlight the need for further research to better understand the interaction between HIV and aging in LMIC.

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Older people living with HIV

The number of older PLWH (age ≥50 years) is predicted to increase by 47% to 6.9 million by 2020 [15]. Despite a growing body of research on HIV and aging in high-income countries, little is known about the intersection of HIV and aging in LMIC, especially in sub-Saharan Africa, which accounted for 62% of newly diagnosed infections among older PLWH in 2016 [16]. Among PLWH in sub-Saharan Africa, 15% are aged at least 50 years, and modeling predicts that by 2040 this proportion will increase to 27% and the number of older PLWH will increase to 9.1 million [17].

Unfortunately, until recently, most population-based HIV prevalence surveys in sub-Saharan Africa have not included older adults, limiting the accuracy of estimates in this age group. Surveys that have included older adults have found a HIV prevalence ranging from 5% among those aged 50–64 years in Kenya, to 13% among those aged 50–54 years in South Africa; in Swaziland, prevalence was 6.4% among adults aged at least 50 years and 13% in men and 7% in women aged 60–64 [18]. A population-based survey in Rwanda that included individuals up to age 59 years found a higher HIV prevalence for most of the older age groups compared with younger age groups [19]. A recent review of data from 40 Demographic Health Surveys (DHS) conducted in 27 sub-Saharan African countries from 2003 to 2012 found that HIV prevalence in adults aged 45–59 years was higher than in the overall adult population for most countries, except for the Democratic Republic of Congo, Ethiopia, Mozambique, Sierra Leone, and Swaziland [20]. In Cameroon, Kenya, Lesotho, Malawi, Niger, and Tanzania, the HIV prevalence in the older age group was above the population average in the most recent survey. Of note, some surveys only included adults up to age 49. The 2015–2018 Population HIV Impact Assessments (PHIAs) being conducted in 15 countries in sub-Saharan African countries and Haiti will include older adults and will shed important light on HIV-related parameters in this population (http://phia.icap.columbia.edu/). Age disaggregated results from the first three country surveys, from Malawi, Zambia, and Zimbabwe show that HIV prevalence tends to be higher among those aged at least 50 years compared with those aged 15–49 years [21–23].

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Comorbid conditions among older people living with HIV

Older PLWH face many of the same health challenges as older individuals in the general population, although the impact of aging may be greater among PLWH. Studies in high-income countries have found that HIV is associated with increased frailty, osteoporotic bone fractures, diabetes, and myocardial infarction [24–27]. Conditions such as diabetes, cardiovascular disease, bone fractures, non-AIDS-defining malignancies, liver disease, and renal failure along with multimorbidity have also been identified at younger ages in PLWH compared with HIV-uninfected adults [28,29].

The reasons for the elevated risk of noncommunicable diseases (NCDs) among PLWH are not entirely understood but increased inflammation because of HIV replication, increased cellular senescence, and the metabolic effect associated with certain antiretroviral drugs may all play a role [30–32]. It is also not clear if HIV accelerates NCD risk (i.e. at the time of HIV infection, the risk of NCDs increases at a faster rate than that in the general population), accentuates HIV risk (i.e. there is a one-time increase in the risk NCDs at the time of HIV infection but no difference in the year-to-year increase in risk), or has both effects [33].

Studies on the association between aging and HIV have had inconsistent findings. This may be because of the fact that PLWH in certain settings having higher rates of chronic disease risk factors such as substance use (smoking, alcohol, drug use) and co-infections (cytomegalovirus, hepatitis B and C viruses), as well as characteristics such as homelessness and social isolation that hinder access to health-related services compared with those without HIV infection [30,32,34]. Even when some of these factors are taken into account, residual confounding likely exists.

The Veterans Aging Cohort Study found that HIV-infected veterans had a higher risk than HIV-uninfected veterans of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer, but these outcomes occurred at similar ages in demographically comparable HIV-uninfected veterans suggesting that HIV did not accelerate aging [35]. A multicohort study comparing age at diagnosis of cancer among PLWH versus the general population found that after adjusting for cancer risk factors, the median age at diagnosis was lower among PLWH for lung, anal, oral cavity/pharynx, and kidney cancers and myeloma but not for other cancers [36]. However, a cohort of HIV-infected and comparable HIV-uninfected participants aged at least 45 from the Netherlands found that PLWH had a significantly higher mean number of age-associated NCDs with rates of hypertension, myocardial infarction, peripheral arterial disease, and impaired renal function significantly higher among PLWH; associations with HIV infection remained significant in adjusted models [37].

In settings with high ART coverage, non-AIDS related conditions have become increasingly important causes of morbidity and mortality among PLWH [38]. A recent multicohort study that included PLWH from Europe, USA, and Australia found that the percentage of deaths attributable to non-AIDS-related cancers increased between 1999–2000 and 2009–2011 [39].

It is important to note that research findings from higher income settings may not apply to resource-constrained settings. Co-occurrence of other acute and chronic infections may differ, as may the prevalence of substance use and other risk factors. In addition, individuals in low-income countries have more limited access to NCD risk reduction interventions and care during their lives, whereas HIV-related stigma in such settings may lead to delays in diagnosis and initiation of ART. Older women and key populations with HIV infection also face unique challenges associated with aging and may require tailored services; however, few aging-related studies have focused on these groups especially in lower income settings [15].

Inflammation is thought to play an important role in aging and is associated with co-infection with cytomegalovirus, hepatitis B and C viruses, malaria, and Mycobacterium tuberculosis, which may result in persistent inflammation even when HIV is well controlled [40]. The prevalence of these infections may be different in higher income versus lower income settings. A recent review article found a pooled prevalence of cytomegalovirus (CMV) infection in Africa of 94.8% among asymptomatic HIV-positive adults compared with 81.8% among HIV-negative adults [41]. Additionally, the African region has a high prevalence of chronic hepatitis B infection at 6.1%, only second in the world to the Western Pacific Region at 6.2% [42].

There is also limited information on NCD risk factors among both PLWH as well as among the general population in lower income settings. Generally, smoking rates are lower in sub-Saharan Africa compared with other parts of the world [43]. However, even with this lower background rate of smoking, there is some evidence that risk factors may be higher in PLWH than in uninfected persons in sub-Saharan Africa, as is noted in wealthier countries. For example, a recent study found that among PLWH attending a clinic in South Africa, 52% of men and 13% of women were smokers, which is higher than in the general population in South Africa (men: 31.9%, women: 7.0%) [44]. Obesity, another NCD risk factor, is a growing problem worldwide including in sub-Saharan Africa [45] and although historically being underweight was the largest concern for PLWH, with effective HIV treatment, high rates of overweight and obesity have been reported [46,47].

Studies in South Africa have found that older PLWH had weaker grip strength compared with similarly aged HIV-uninfected adults [48] and that biological markers of aging were increased in the former group [49]. In a study from Uganda among older PLWH on ART, similar health and functional status were reported among older individuals with and without HIV infection when controlling for other variables, with the exception of reported lower BMI among PLWH [50]. Another study in Uganda of older PLWH and older HIV-uninfected adults found that PLWH were more likely to have chronic obstructive pulmonary disease (COPD) and eye problems (except for those aged 60–69 years) though diabetes and angina were more prevalent in the HIV-uninfected participants [51]. The latter study also found that no difference existed between PLWH and HIV-uninfected participants in having one or more chronic conditions or in disability scores. A recent large study conducted in South Africa found that PLWH persons over 40 years were less likely to have hypertension, diabetes, or be overweight or obese and to have multiple cardiometabolic disease comorbidities compared with HIV-negative persons [52]. However, adjusted analyses were not presented in the latter study. Mixed findings to date from studies conducted in sub-Saharan Africa may also be because of systematic differences between PLHIV and HIV-uninfected populations that result in residual confounding.

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HIV and non-HIV disease management in older people living with HIV

Management of HIV and other health conditions can be more complex in older PLWH [53]. ART side effects may be more severe, and ART may exacerbate or increase the risk of other conditions such as kidney disease, declines in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction [54,55]. In addition, older PLWH are likely to already have comorbid conditions such as cardiovascular, renal, and liver disease, which has the potential to complicate the management of HIV disease because of challenges related to polypharmacy and drug–drug interactions [56,57]. Although ART adherence is generally better among older PLWH, cognitive impairment associated with aging may affect adherence [56,58]. Furthermore, upon initiating HIV treatment, older adults do not experience the same magnitude in CD4+ cell count recovery as younger adults, thus leading to their continued vulnerability to various complications – a finding noted repeatedly in both higher income settings [59,60] and in studies from sub-Saharan Africa [61–67]. This is compounded by the finding that delayed ART initiation has been associated more strongly with mortality in older compared with younger adults [68].

Despite the rapidly increasing prevalence of NCDs in lower income countries [69], their health systems are often not optimized to deliver chronic care, and the resources needed to screen, diagnose, and manage NCDs and other non-AIDS related conditions relevant to older PLWH are frequently limited [70]. Extending the lessons learned from the successful scale-up of HIV services to NCD programs may accelerate the creation of effective NCD services for both PLWH and the general population. Examples include the use of a public health approach to NCD program design, focusing on evidence-based algorithmic management to enable task shifting to nonphysician clinicians, and to simplify the procurement of medications and laboratory supplies [70–72]. Other lessons from HIV programs include the need for systematic outreach to communities to increase demand for NCD services, clinician training, provision of psychosocial support to enhance adherence to medications and retention in care, and the use of simple monitoring and evaluation indicators to measure performance along the cascade from diagnosis to effective treatment [73]. It is increasingly clear that integration of routine NCD screening, prevention, and treatment services into HIV programs is an effective way to identify and treat PLWH with NCDs [74].

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Risk of HIV acquisition among older individuals

Although older adults continue to be at risk for HIV acquisition, with evidence of ongoing sexual activity and low condom use [75–80], the lack of awareness by healthcare providers of HIV risk among this age group limits their access to HIV testing and prevention interventions, thus increasing the likelihood of unrecognized HIV infection [81,82]. Even though opt-out HIV testing is recommended in the United States for all patients in healthcare settings, very few (<5%) older adults report receiving a HIV test [83] and testing rates are lower compared to younger adults, even at venues where HIV prevalence is relatively high, such as needle exchange sites and sexually transmitted infection clinics [84]. The same findings have been noted in sub-Saharan Africa [85]. A recent systematic review found that behavioral interventions to reduce HIV risk among older adults were lacking [77]. Major challenges to providing HIV education for older adults include the following: ageism among health professionals, reluctance among older adults to discuss sexuality, and misconceptions among older adults about their own HIV risk [86].

There are few studies that assessed HIV incidence among older adults in sub-Saharan Africa and only one with data from the last 5 years in the context of ART scale-up. One open cohort study from Zimbabwe conducted from 1998 to 2011 found an incidence of 0.708 per 100 person-years in adults at least 45 years of age, with high rate among men compared with women (1.03 versus 0.57) [79]. A study conducted in South Africa from 2006 to 2008 found that HIV incidence among adults aged at least 50 years was 0.5 (95% CI 0.3–1.0) per 100 person-years, with rates not significantly higher in men compared with women (0.9 versus 0.4 per 100 person-years) [87]. A recently published nationally representative survey from Rwanda found that HIV incidence was higher among individuals between 36 and 45 years of age compared with those between 16 and 25 years of age [19].

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Conclusion

Populations around the world are aging, with associated societal, economic, and health challenges [88,89]. Unfortunately, older PLWH face unique challenges in accessing the services they need (Table 1). In lower income countries, many of which will be bearing the largest burden of aging PLWH, more research is needed on HIV disease among older individuals. Cohort studies that include a sufficient number of older PLWH from these settings are needed to examine the interaction of HIV and aging over their life course. Surveillance and surveys should also include sufficient number of older PLWH to enable accurate estimates of HIV prevalence and incidence. Additionally, program data should be disaggregated by age and sex, enabling routine reporting on older PLWH.

HIV programs should also ensure that older PLWH have access to non-HIV clinical services and to appropriate supportive services responsive to their needs. Lastly, HIV prevention efforts must not overlook older adults and should acknowledge their sexuality and their needs for tailored prevention messages, tools, and services. Only with such concerted efforts can the global community do justice to the needs of older PLWH and protect older individuals from acquiring HIV infection. Now is the opportune time to embark on vigorous efforts to confront this threat, to ensure that older individuals with HIV can live long and healthy lives into older age, and to end the threat of HIV in this population.

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Acknowledgements

All authors contributed to the conception, writing, and review of the manuscript.

The authors wish to thank Katherine Harripersaud and Joseph Stegemerten for their contributions.

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Conflicts of interest

There are no conflicts of interest.

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References

1. Samji H, Cescon A, Hogg RS, Modur SP, Althoff KN, Buchacz K, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One 2013; 8:e81355.
2. Teeraananchai S, Kerr SJ, Amin J, Ruxrungtham K, Law MG. Life expectancy of HIV-positive people after starting combination antiretroviral therapy: a meta-analysis. HIV Med 2017; 18:256–266.
3. Antiretroviral Therapy Cohort CollaborationSurvival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV 2017; 4:e349–e356.
4. Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS 2016; 11:492–500.
5. Nakagawa F, May M, Phillips A. Life expectancy living with HIV: recent estimates and future implications. Curr Opin Infect Dis 2013; 26:17–25.
6. Hogg RS, Eyawo O, Collins AB, Zhang W, Jabbari S, Hull MW, et al. Comparative Outcomes And Service Utilization Trends (COAST) studyHealth-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study. Lancet HIV 2017; 4:e270–e276.
7. May MT, Gompels M, Delpech V, Porter K, Orkin C, Kegg S, et al. UK Collaborative HIV Cohort (UK CHIC) StudyImpact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS 2014; 28:1193–1202.
8. GBD 2013 Mortality and Causes of Death CollaboratorsGlobal, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385:117–171.
9. Price AJ, Glynn J, Chihana M, Kayuni N, Floyd S, Slaymaker E, et al. Sustained 10-year gain in adult life expectancy following antiretroviral therapy roll-out in rural Malawi: July 2005 to June 2014. Int J Epidemiol 2017; 46:479–491.
10. Reniers G, Blom S, Calvert C, Martin-Onraet A, Herbst AJ, Eaton JW, et al. Trends in the burden of HIV mortality after roll-out of antiretroviral therapy in KwaZulu-Natal, South Africa: an observational community cohort study. Lancet HIV 2017; 4:e113–e121.
11. Mills EJ, Bakanda C, Birungi J, Chan K, Ford N, Cooper CL, 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.
12. Asiki G, Reniers G, Newton R, Baisley K, Nakiyingi-Miiro J, Slaymaker E, et al. Adult life expectancy trends in the era of antiretroviral treatment in rural Uganda (1991-2012). AIDS 2016; 30:487–493.
13. Joint United Nations Programme on HIV/AIDS. 90-90-90 an ambitious treatment target to help end the AIDS epidemic, 2014. Available at: http://www.unaids.org/en/resources/documents/2017/90-90-90. [Accessed 16 January 2018].
14. Joint United Nations Programme on HIV/AIDS (UNAIDS). Ending AIDS: progress towards the 90–90–90 targets, 2017. Available at: http://www.unaids.org/sites/default/files/media_asset/Global_AIDS_update_2017_en.pdf. [Accessed 16 January 2018].
15. UNAIDS. Get on the fast-track, the life-cycle approach to HIV 2016. Available at: http://www.unaids.org/sites/default/files/media_asset/Get-on-the-Fast-Track_en.pdf. [Accessed 10 October 2017].
16. UNAIDS. AIDS data, 2016. Available at: http://aidsinfo.unaids.org/. [Accessed 10 October 2017].
17. Hontelez JA, de Vlas SJ, Baltussen R, Newell ML, Bakker R, Tanser F, 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.
18. UNAIDS. Joint United Nations Programme on HIV/AIDS (UNAIDS). HIV and Aging. A special supplement to the UNAIDS report on the global AIDS epidemic 2013. Available at: http://www.unaids.org/sites/default/files/en/media/unaids/contentassets/documents/unaidspublication/2013/20131101_JC2563_hiv-and-aging_en.pdf. [Accessed 10 October 2017].
19. Nsanzimana S, Remera E, Kanters S, Mulindabigwi A, Suthar AB, Uwizihiwe JP, et al. Household survey of HIV incidence in Rwanda: a national observational cohort study. Lancet HIV 2017; 4:e457–e464.
20. Vollmer S, Harttgen K, Alfven T, Padayachy J, Ghys P, Barnighausen T. The HIV epidemic in sub-Saharan Africa is aging: evidence from the demographic and health surveys in sub-Saharan Africa. AIDS Behav 2017; 21:101–113.
21. Ministry of Health, Malawi. Malawi POPULATION-based HIV Impact Assessment (MPHIA) 2015-16: First Report, 2017. Available at: http://phia.icap.columbia.edu/wp-content/uploads/2017/11/Final-MPHIA-First-Report_11.15.17.pdf. [Accessed 25 January 2018].
22. Ministry of Health, Zambia. Zambia Population-based HIV Impact Assessment (ZAMPHIA) 2016: First Report, 2017. Available at: http://phia.icap.columbia.edu/wp-content/uploads/2017/11/FINAL-ZAMPHIA-First-Report_11.30.17_CK.pdf. [Accessed 25 January 2018].
23. Ministry of Health and Child Care (MOHCC), Zimbabwe. Zimbabwe Population-Based HIV Impact Assessment (ZIMPHIA) 2015-16: First Report, 2017. Available at: http://phia.icap.columbia.edu/wp-content/uploads/2017/11/ZIMPHIA_First_Report_FINAL.pdf. [Accessed 25 January 2018].
24. Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci 2007; 62:1279–1286.
25. Justice AC, Braithwaite RS. Lessons learned from the first wave of aging with HIV. AIDS 2012; 26 (suppl 1):S11–S18.
26. Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med 2005; 165:1179–1184.
27. Van Epps P, Kalayjian RC. Human immunodeficiency virus and aging in the era of effective antiretroviral therapy. Infect Dis Clin North Am 2017; 31:791–810.
28. Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 2011; 53:1120–1126.
29. Goulet JL, Fultz SL, Rimland D, Butt A, Gibert C, Rodriguez-Barradas M, et al. Aging and infectious diseases: do patterns of comorbidity vary by HIV status, age, and HIV severity?. Clin Infect Dis 2007; 45:1593–1601.
30. High KP, Brennan-Ing M, Clifford DB, Cohen MH, Currier J, Deeks SG, et al. OAR Working Group on HIV and Aging. HIV and aging: state of knowledge and areas of critical need for researchHIV and aging: state of knowledge and areas of critical need for research. A report to the NIH Office of AIDS Research by the HIV and Aging Working Group. J Acquir Immune Defic Syndr 2012; 60 (suppl 1):S1–S18.
31. Justice AC. HIV and aging: time for a new paradigm. Curr HIV/AIDS Rep 2010; 7:69–76.
32. Pathai S, Bajillan H, Landay AL, High KP. Is HIV a model of accelerated or accentuated aging?. J Gerontol A Biol Sci Med Sci 2014; 69:833–842.
33. Sabin CA, Reiss P. Epidemiology of ageing with HIV: what can we learn from cohorts?. AIDS 2017; 31 (suppl 2):S121–S128.
34. Justice AC, Modur SP, Tate JP, Althoff KN, Jacobson LP, Gebo KA, et al. NA-ACCORD and VACS Project TeamsPredictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: a North American cross cohort analysis. J Acquir Immune Defic Syndr 2013; 62:149–163.
35. Althoff KN, McGinnis KA, Wyatt CM, Freiberg MS, Gilbert C, Oursler KK, et al. Veterans Aging Cohort Study (VACS)Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis 2015; 60:627–638.
36. Shiels MS, Althoff KN, Pfeiffer RM, Achenbach CJ, Abraham AG, Castilho J, et al. North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA). HIV infection, immunosuppression, and age at diagnosis of non-AIDS-defining cancersHIV infection, immunosuppression, and age at diagnosis of non-AIDS-defining cancers. Clin Infect Dis 2017; 64:468–475.
37. Schouten J, Wit FW, Stolte IG, Kootstra NA, van der Valk M, Geerlings SE, et al. AGEhIV Cohort Study GroupCross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis 2014; 59:1787–1797.
38. Hasse B, Ledergerber B, Furrer H, Battegay M, Hirschel B, Cavassini M, et al. Swiss HIV Cohort StudyMorbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis 2011; 53:1130–1139.
39. Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. D:A:D Study GroupTrends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 2014; 384:241–248.
40. Lagathu C, Cossarizza A, Bereziat V, Nasi M, Capeau J, Pinti M. Basic science and pathogenesis of ageing with HIV: potential mechanisms and biomarkers. AIDS 2017; 31 (suppl 2):S105–S119.
41. Bates M, Brantsaeter AB. Human cytomegalovirus (CMV) in Africa: a neglected but important pathogen. J Virus Erad 2016; 2:136–142.
42. World Health Organization. Global Hepatitis Report, 2017. Available at: http://who.int/hepatitis/publications/global-hepatitis-report2017/en/. [Accessed 19 January 2018].
43. Ansara DL, Arnold F, Kishor S, Hsia J, Kaufmann R. Tobacco use by men and women in 49 countries with demographic and health surveys, 2013. Available at: https://dhsprogram.com/pubs/pdf/CR31/CR31.pdf. [Accessed 17 January 2018].
44. Elf JL, Variava E, Chon S, Lebina L, Motlhaoleng K, Gupte N, et al. Prevalence and correlates of smoking among people living with HIV in South Africa. Nicotine Tob Res 2017; [Epub ahead of print].
45. Neupane S, Prakash KC, Doku DT. Overweight and obesity among women: analysis of demographic and health survey data from 32 Sub-Saharan African Countries. BMC Public Health 2016; 16:30.
46. Wand H, Ramjee G. High prevalence of obesity among women who enrolled in HIV prevention trials in KwaZulu-Natal, South Africa: healthy diet and life style messages should be integrated into HIV prevention programs. BMC Public Health 2013; 13:159.
47. Guehi C, Badje A, Gabillard D, Ouattara E, Koule SO, Moh R, et al. High prevalence of being Overweight and Obese HIV-infected persons, before and after 24 months on early ART in the ANRS 12136 Temprano Trial. AIDS Res Ther 2016; 13:12.
48. Negin J, Martiniuk A, Cumming RG, Naidoo N, Phaswana-Mafuya N, Madurai L, et al. Prevalence of HIV and chronic comorbidities among older adults. AIDS 2012; 26 (suppl 1):S55–S63.
49. Pathai S, Lawn SD, Gilbert CE, McGuinness D, McGlynn L, Weiss HA, et al. Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study. AIDS 2013; 27:2375–2384.
50. Scholten F, Mugisha J, Seeley J, Kinyanda E, Nakubukwa S, Kowal P, et al. Health and functional status among older people with HIV/AIDS in Uganda. BMC Public Health 2011; 11:886.
51. Mugisha JO, Schatz EJ, Randell M, Kuteesa M, Kowal P, Negin J, et al. Chronic disease, risk factors and disability in adults aged 50 and above living with and without HIV: findings from the Wellbeing of Older People Study in Uganda. Glob Health Action 2016; 9:31098.
52. Gaziano TA, Abrahams-Gessel S, Gomez-Olive FX, Wade A, Crowther NJ, Alam S, et al. Cardiometabolic risk in a population of older adults with multiple co-morbidities in rural south africa: the HAALSI (Health and Aging in Africa: longitudinal studies of INDEPTH communities) study. BMC Public Health 2017; 17:206.
53. Guaraldi G, Palella FJ Jr. Clinical implications of aging with HIV infection: perspectives and the future medical care agenda. AIDS 2017; 31 (suppl 2):S129–S135.
54. Burgess MJ, Zeuli JD, Kasten MJ. Management of HIV/AIDS in older patients-drug/drug interactions and adherence to antiretroviral therapy. HIV AIDS (Auckl) 2015; 7:251–264.
55. Jourjy J, Dahl K, Huesgen E. Antiretroviral treatment efficacy and safety in older HIV-infected adults. Pharmacotherapy 2015; 35:1140–1151.
56. Nachega JB, Hsu AJ, Uthman OA, Spinewine A, Pham PA. Antiretroviral therapy adherence and drug-drug interactions in the aging HIV population. AIDS 2012; 26 (suppl 1):S39–S53.
57. Greene M, Justice AC, Lampiris HW, Valcour V. Management of human immunodeficiency virus infection in advanced age. JAMA 2013; 309:1397–1405.
58. Hinkin CH, Hardy DJ, Mason KI, Castellon SA, Durvasula RS, Lam MN, et al. Medication adherence in HIV-infected adults: effect of patient age, cognitive status, and substance abuse. AIDS 2004; 18 (suppl 1):S19–S25.
59. Goetz MB, Boscardin WJ, Wiley D, Alkasspooles S. Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy. AIDS 2001; 15:1576–1579.
60. Sabin CA, Smith CJ, d’Arminio Monforte A, Battegay M, Gabiano C, et al. Collaboration of Observational HIVERESGResponse to combination antiretroviral therapy: variation by age. AIDS 2008; 22:1463–1473.
61. Eduardo E, Lamb MR, Kandula S, Howard A, Mugisha V, Kimanga D, et al. Characteristics and outcomes among older HIV-positive adults enrolled in HIV programs in four sub-Saharan African countries. PLoS One 2014; 9:e103864.
62. Crawford KW, Wakabi S, Magala F, Kibuuka H, Liu M, Hamm TE. Evaluation of treatment outcomes for patients on first-line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses. HIV Med 2015; 16:95–104.
63. Vinikoor MJ, Joseph J, Mwale J, Marx MA, Goma FM, Mulenga LB, et al. Age at antiretroviral therapy initiation predicts immune recovery, death, and loss to follow-up among HIV-infected adults in urban Zambia. AIDS Res Hum Retroviruses 2014; 30:949–955.
64. Kanters S, Nachega J, Funk A, Mukasa B, Montaner JS, Ford N, et al. CD4(+) T-cell recovery after initiation of antiretroviral therapy in a resource-limited setting: a prospective cohort analysis. Antivir Ther 2014; 19:31–39.
65. Balestre E, Eholie SP, Lokossue A, Sow PS, Charurat M, Minga A, et al. International epidemiological Database to Evaluate AIDS (IeDEA) West Africa CollaborationEffect of age on immunological response in the first year of antiretroviral therapy in HIV-1-infected adults in West Africa. AIDS 2012; 26:951–957.
66. Greig J, Casas EC, O’Brien DP, Mills EJ, Ford N. Association between older age and adverse outcomes on antiretroviral therapy: a cohort analysis of programme data from nine countries. AIDS 2012; 26 (suppl 1):S31–S37.
67. Semeere AS, Lwanga I, Sempa J, Parikh S, Nakasujja N, Cumming R, et al. Mortality and immunological recovery among older adults on antiretroviral therapy at a large urban HIV clinic in Kampala, Uganda. J Acquir Immune Defic Syndr 2014; 67:382–389.
68. Edwards JK, Cole SR, Westreich D, Mugavero MJ, Eron JJ, Moore RD, et al. Centers for AIDS Research Network of Integrated Clinical Systems investigatorsAge at entry into care, timing of antiretroviral therapy initiation, and 10-year mortality among HIV-seropositive adults in the United States. Clin Infect Dis 2015; 61:1189–1195.
69. World Health Organization. Projections of mortality and causes of death, 2015 and 2030. Available from: http://www.who.int/healthinfo/global_burden_disease/projections/en/. [Accessed 19 October 2017].
70. Rabkin M, Kruk ME, El-Sadr WM. HIV, aging and continuity care: strengthening health systems to support services for noncommunicable diseases in low-income countries. AIDS 2012; 26 (suppl 1):S77–S83.
71. Palma AM, Rabkin M, Nuwagaba-Biribonwoha H, Bongomin P, Lukhele N, Dlamini X, et al. Can the success of HIV scale-up advance the global chronic NCD agenda?. Glob Heart 2016; 11:403–408.
72. Rabkin M, El-Sadr WM. Why reinvent the wheel? Leveraging the lessons of HIV scale-up to confront noncommunicable diseases. Glob Public Health 2011; 6:247–256.
73. Rabkin M, Nishtar S. Scaling up chronic care systems: leveraging HIV programs to support noncommunicable disease services. J Acquir Immune Defic Syndr 2011; 57 (suppl 2):S87–S90.
74. Rabkin M, Mutiti A, Chung C, Zhang Y, Wei Y, El-Sadr WM. Missed opportunities to address cardiovascular disease risk factors amongst adults attending an urban HIV clinic in South Africa. PLoS One 2015; 10:e0140298.
75. Rosenberg MS, Gomez-Olive FX, Rohr JK, Houle BC, Kabudula CW, Wagner RG, 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.
76. Freeman E, Anglewicz P. HIV prevalence and sexual behaviour at older ages in rural Malawi. Int J STD AIDS 2012; 23:490–496.
77. Negin J, Rozea A, Martiniuk AL. HIV behavioural interventions targeted towards older adults: a systematic review. BMC Public Health 2014; 14:507.
78. Mojola SA, Williams J, Angotti N, Gomez-Olive FX. HIV after 40 in rural South Africa: a life course approach to HIV vulnerability among middle aged and older adults. Soc Sci Med 2015; 143:204–212.
79. Negin J, Gregson S, Eaton JW, Schur N, Takaruza A, Mason P, et al. Rising levels of HIV infection in older adults in Eastern Zimbabwe. PLoS One 2016; 11:e0162967.
80. UNAIDS. The Joint United Nations Programme on HIV/AIDS (UNAIDS). The Gap Report 2014: People aged 50 years and older. Available at: http://www.unaids.org/sites/default/files/media_asset/12_Peopleaged50yearsandolder.pdf. [Accessed 10 October 2017].
81. Brooks JT, Buchacz K, Gebo KA, Mermin J. HIV infection and older Americans: the public health perspective. Am J Public Health 2012; 102:1516–1526.
82. el-Sadr W, Gettler J. Unrecognized human immunodeficiency virus infection in the elderly. Arch Intern Med 1995; 155:184–186.
83. Ford CL, Godette DC, Mulatu MS, Gaines TL. Recent HIV testing prevalence, determinants, and disparities among U.S. older adult respondents to the behavioral risk factor surveillance system. Sex Transm Dis 2015; 42:405–410.
84. Ford CL, Lee SJ, Wallace SP, Nakazono T, Newman PA, Cunningham WE. HIV testing among clients in high HIV prevalence venues: disparities between older and younger adults. AIDS Care 2015; 27:189–197.
85. Negin J, Nemser B, Cumming R, Lelerai E, Ben Amor Y, Pronyk P. HIV attitudes, awareness and testing among older adults in Africa. AIDS Behav 2012; 16:63–68.
86. Milaszewski D, Greto E, Klochkov T, Fuller-Thomson E. A systematic review of education for the prevention of HIV/AIDS among older adults. J Evid Based Soc Work 2012; 9:213–230.
87. Wallrauch C, Barnighausen T, Newell ML. HIV prevalence and incidence in people 50 years and older in rural South Africa. S Afr Med J 2010; 100:812–814.
88. United Nations Department of Economic and Social Affairs Population Division. World Population Ageing, 2015. Available at: http://www.un.org/en/development/desa/population/publications/pdf/ageing/WPA2015_Report.pdf. [Accessed 20 November 2017].
89. National Institute on Aging, National Institutes of Health, U.S. Department of Health and Human Services. Why Population Aging Matters, A Global Perspective, 2007. Available at: https://www.nia.nih.gov/sites/default/files/2017-06/WPAM.pdf. [Accessed 20 November 2017].
Keywords:

aging; chronic disease; comorbidity; frailty; HIV; multimorbidity; social support

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