HIV and Africa's elderly: the problems and possibilities : AIDS

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HIV and Africa's elderly

the problems and possibilities

Bendavid, Erana,b; Ford, Nathanc,d; Mills, Edward J.e

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doi: 10.1097/QAD.0b013e3283558513
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Abstract

Introduction

Between 1990 and 2005, the HIV epidemic was associated with declining life expectancy in most countries of southern Africa [1]. The disease was responsible for greatly increasing mortality among young men and women [2]. As a result, the survival prospects of a Zambian newborn were similar in 1950 and 2001 (whereas life expectancy at birth increased by nearly 10 years in most other regions of the world over the same period) [3]. Over the past decade, however, the expansion of antiretroviral therapy (ART), the stabilizing prevalence of HIV, and decreasing disease incidence resulted in rising life expectancies throughout Africa [1,4]. Ugandans receiving ART today have a life expectancy that is about 70% as long as that of HIV-uninfected individuals [5].

An under-appreciated implication of these changes is that countries throughout Africa are facing rapidly aging populations of both infected and uninfected individuals. With increasing access to ART, the number of adults over the age of 60 in Africa is projected to rise by 55% between 2010 and 2025, a 135% increase since 1995 [1,6]. This article summarizes the challenges related to HIV among Africa's elderly, and lays out a research agenda for improved understanding and care of this growing and under-recognized population. Because most epidemiologic measures stop at age of 49, we refer to individuals older than 50 years old who live in sub-Saharan Africa as older Africans, a definition also used by WHO [7].

HIV burden among older Africans

Prevalence of HIV is one of the most closely monitored measures of disease burden and epidemic spread in Africa. Two important reasons for its dominance are the accuracy in HIV testing technologies, and the ability to obtain a meaningful estimate with cross-sectional measurements. Most estimates of HIV prevalence in sub-Saharan Africa come from two primary sources: antenatal clinic surveillance, and nationally representative household serosurveys such as the Demographic and Health Surveys (DHS) [8,9]. In general, neither source provides information on HIV prevalence among adults older than 49 years old. Antenatal surveillance sites measure prevalence among pregnant women, whereas DHS and related surveys restrict HIV testing to men and women between the ages of 15 and 49 years (a few DHS surveys measure HIV prevalence among a nonrepresentative sample of men up to age 60). Although the decision to focus on the most heavily affected sectors of the population provided critical information for monitoring the epidemic, it leaves researchers and policymakers unable to estimate and meet the needs of older populations.

Very few HIV surveys that estimate prevalence among older Africans have been completed. South Africa conducts repeated nationally representative HIV prevalence surveys every 4–5 years (most recently in 2008–2009) [10,11]. In the most recent survey, HIV prevalence among men and women between 50 and 60 years old was over 8%, higher than among men in the age group between 20 and 24 years old and women 15 to 19 years old. Kenya's AIDS Indicator Survey measures HIV prevalence up to the age of 64. Among Kenyans between 50 and 64 years old in 2007, HIV prevalence was 5.0% (compared with 7.4% in the 15–49 age group) [12]. In the most recent South African and Kenyan surveys, prevalence among older individuals had increased compared with previous surveys. To the best of our knowledge, no other nationally representative serosurveys have quantified the burden among older Africans.

Although not nationally representative, several high-quality surveillance sites measure HIV prevalence without an age ceiling. These include demographic surveillance sites such as those in Hlabisa (South Africa), Agincourt (South Africa), Butajira (Ethiopia), Kisumu (Kenya), and Rakai (Uganda) [13–16]. HIV prevalence in older populations has increased in several of these sites, but there is little understanding of what drives this trend. An intuitive explanation may be the improved survival of individuals with HIV. That is, prevalence at a given age group is influenced by the number of infected people entering and leaving the age group, and expanded ART coverage means that more infected individuals are entering older ages, while fewer are dying. It may also be that the rate of new HIV infections in this age group is higher than commonly believed, possibly because of an under-appreciation of risk and few prevention resources targeting this group. Understanding the drivers of the elevated HIV prevalence in this age group is important because different epidemiological drivers carry different policy implications. If high incidence explains the rising prevalence, for example, then addressing that issue might involve the design of HIV prevention services that place greater emphasis on older individuals.

Older individuals in HIV treatment programs

The treatment of HIV/AIDS in older age groups, particularly in high-burden countries of sub-Saharan Africa, has received relatively little attention. This has partly been due to a lack of perceived relevance for countries where life expectancy at birth among the general population is low: with the exception of Namibia, life expectancy at birth in the 10 countries with highest HIV prevalence is below 55 years [17]. However, reports from ART cohorts suggest that in fact older people represent a substantial proportion of the population attending treatment facilities. In a recent report from a multicenter cohort across nine sub-Saharan African countries over 11% of people on ART (1977 of 17 561 patients) were at least 50 years old [17]. A similar proportion was reported from cohorts in Uganda, where 11% of patients (2430 of 22 087) were older than 50 years, and South Africa, where 15% of patients (8040 of 52217) were older than 45 years; in this latter report, the mean age at enrollment increased with each successive year of the program [18–20].

Several studies, from both developed and developing country settings, have found that CD4 reconstitution is significantly slower among older patients [17,21]. This underscores the importance of preventing delays in treatment initiation, as older individuals are expected to reach a lower peak CD4 cell on treatment compared with younger individuals, all things being equal. Although the balance of risks and benefits of early ART initiation (earlier than a CD4 cell count of 500 cells/μl) is not fully known, the lower immune reconstitution suggests older individuals may derive greater benefits from early treatment initiation compared with younger individuals.

Clinical considerations unique to older HIV-infected individuals

Demographic projections for Africa and current transitions in rapidly developing countries such as India and China indicate that chronic diseases associated with aging both impose a high burden and receive relatively less attention [22]. This poses a triple threat for older HIV-infected Africans: HIV risk is probably underestimated, chronic disease receives little attention, and HIV is associated with high risk of age-related comorbid chronic illnesses. Experience in developed countries shows that HIV-infected individuals suffer an increase in many age-associated comorbidities, including cardiovascular disease (CVD) and neurocognitive decline [23,24]. As these conditions occur earlier and with greater frequency among HIV-infected individuals compared with uninfected individuals, HIV has been hypothesized to lead to ‘early’ or ‘accelerated’ aging [25].

Cardiovascular disease

CVD poses a unique and complex management issue for older adults with HIV. Numerous pathways are known or thought to increase the risk of CVD among infected individuals. Viral replication and ongoing inflammation during untreated HIV are thought to intrinsically increase risk of CVD, especially atherosclerosis. In addition, many antiretrovirals in common use lead to metabolic changes that increase CVD risk. Specifically, lopinavir/ritonavir and stavudine, commonly used drugs in sub-Saharan Africa, are known to significantly increase low-density lipoprotein, as well as lead to metabolic changes that lead to insulin resistance, further increasing risk of CVD [26,27]. Finally, recent evidence suggests a possible role for ART in increasing the risk of myocardial infarctions independent of any metabolic or cholesterol changes [28]. These risks interact significantly with age-related risk of CVD, and pose unique risks and complex management issues for the care of older HIV-infected individuals.

Neurologic and psychiatric conditions

Studies among the US veteran population have shown that prevalence of depressive symptoms, alcohol abuse or dependence, and drug abuse or dependence are higher among HIV-infected veterans compared with age-matched, HIV-uninfected controls [29]. Other literature also supports these findings, noting a higher prevalence of major depressive disorder and subsyndromal depressive symptomatology among HIV-infected patients, across continents and HIV risk groups, as compared to the general population [30]. The burden of neurologic and psychiatric comorbidity may be disproportionately represented among older individuals with HIV, as evidence in the USA, which suggests that this group carries a large burden of undiagnosed or untreated depression [31].

Oncologic conditions

Elderly patients are at higher risk for cancer. The National Cancer Institute of the USA notes that the overall risk for cancer among those over the age of 65 is 10 times higher than among the younger population in the USA [32,33]. Among a small cohort (n=162) of HIV-infected and HIV-uninfected patients in Botswana (85 HIV-infected), HIV-infected patients were at increased risk of certain cancers, particularly AIDS-defining cancers such as Kaposi's sarcoma, cervical cancer, and anal and non-Hodgkin's lymphoma [34]. HIV-infected patients tended to be younger, presented more frequently with advanced stage cancers, and were on ART but not receiving cancer treatments. Non-AIDS-defining malignancies accounted for 43% of all cancers.

Musculoskeletal conditions

Reduced bone mineral density is associated with the use of certain key antiretroviral drugs [35,36]. Other studies have shown that, even when controlling for ART regimen, HIV-infected patients seem to have a higher rate of osteoporosis when compared with a similar HIV-uninfected population, implying that the disease itself may have some effect on bone mineral density [37,38]. These factors are of particular concern considering that loss of bone mineral density, one of the most important risk factors for fracture, is a general feature of aging [39].

Much of our understanding on the aging processes accelerated by HIV came from USA and Europe. Even in these settings, however, there is great uncertainty about their prevalence and burden. In Africa, where even less is known about non-AIDS events and conditions, the progression of HIV/AIDS and associated morbidities urgently needs better characterization.

Potential intervention points

HIV in older Africans has been under-recognized to date. Most treatment, prevention, and care programs target young adults and children, and older individuals may be left out because the disease burden may not be recognized, because policy and program specifications may not favor the enrollment and retention of older individuals, because of resource constraints that direct resources toward younger age groups or those perceived to be at higher risk, or because older individuals may not demand HIV prevention and treatment services.

A number of intervention points with potentially large health and welfare benefits are presently available to respond to HIV in older patients. First, a clear potential intervention is an expansion of ART services to identify, target, retain, and treat older individuals. Timely initiation of ART is all the more important for older patients given the reduced immune reconstitution. Past experience shows that CD4 cell count response to ART is less robust with increasing age [21,40]. For that reason, older age is a possible indication for initiation of ART at a higher CD4 threshold than recommended for younger adults, as for other groups of patients at higher risk of death [41]. This has recently been recognized by the latest US Department of Health and Human Services guidelines, which recommend immediate initiation of ART in HIV-infected individuals aged above 50 years irrespective of CD4 cell count [42].

Second, if further epidemiological research suggests ongoing transmission of HIV in older ages, prevention interventions could effectively mitigate the burden of disease in this population. Evidence-based HIV prevention modalities, including male circumcision, ART in discordant or high-risk partnerships, and (potentially) pre-exposure prophylaxis, have expanded the options for HIV prevention in the past few years. All of these would be appropriate for older individuals and could have a substantial effect of the epidemic.

Third, novel technologies aimed at reducing cardiac and cancer comorbidities among the elderly in other settings could be effective and cost-effective for older infected Africans. One approach that is currently being tested in both HIV and non-HIV populations is a cardiovascular polypill. The idea of a polypill to reduce cardiovascular deaths was first proposed by Yusuf [43] in 2002, and in a more detailed manner, by Wald and Law in 2004 [44]. A polypill could include effective and inexpensive drugs to reduce cardiovascular and cancer risks. A polypill is being evaluated in a large randomized trial of the general population in India that includes a low-dose statin, three blood pressure drugs, and aspirin [45]. The same type of trial has been proposed in HIV patients and recent funding is expanding the Indian trial into Africa among an HIV-infected population [46].

Recent evidence suggests that a polypill could have a role in reducing both cardiovascular and also cancer deaths, conditions with a unique burden among older HIV-infected individuals [47,48]. Although the role of statins, blood pressure drugs, and aspirin are well recognized in CVDs, recent evidence suggests that aspirin reduces the risk of cancer death as well. Table 1[49–52] demonstrates the individual drug effects on major non-AIDS-defining outcomes.

T1-10
Table 1:
Estimated treatment effects of individual components of a polypill on HIV/AIDS patients.

The health benefits of a polypill among older infected Africans can be substantial. Several important evaluations from western settings indicate high levels of non-AIDS deaths. A recent publication by the Swiss cohort provided mortality and morbidity results in aging populations [53]. From this article, all-cause mortality for 50–64 year olds was estimated to be 9.66 [95% confidence interval (CI) 7.47–12.50] deaths per 1000 person-years. Of these, roughly 2.23 deaths per 1000 person-years were caused by non-AIDS-defining malignancies and 1.20 deaths per 1000 person-years were cardiovascular in origin.

The rates of non-AIDS events in Africa are thought to be about twice that of western settings, partially explained by higher rates of tuberculosis (TB) at higher CD4 cell counts in Africa compared with placed with lower TB endemicity [41,54]. However, the study providing this information was limited by small sample sizes and a small number of events; in general, evidence from Africa on non-AIDS diseases is poor, especially at higher CD4 cell counts. If we assume a cardiovascular death rate of 2.40 per 1000 person-years, and a cancer death rate of 4.5 deaths per 1000 person-years, then adding up the expected reduction in deaths (and their CI limits) yields a combined reduction in cardiovascular and cancer deaths of 1.5 (95% CI 0.9–2.2) for secondary cardiac prevention, and 0.9 (95% CI 0.5–2.0) for primary prevention. If CVD and cancer are associated with a combined death rate of seven deaths per 1000 patient-years, then a polypill could reduce the associated mortality to 5.5 deaths per 1000 patient-years (95% CI 4.8–6.1) for secondary prevention and 6.1 deaths per 1000 patient-years (95% CI 5.0–6.5) for primary prevention. Thus, assuming that the uncertainty bounds used in this projected analysis are accurate and that the addition of each polypill component is additive, a polypill-containing inexpensive and widely available drugs could reduce non-AIDS-defining deaths by cancer and CVD by approximately 20%.

Benefits of reduced HIV incidence and morbidity in older populations

Identifying the burden of disease and appropriately directing resources at the management of HIV among older Africans could have several direct and indirect benefits. Reducing morbidity and mortality in this age group could be a direct result of more appropriate identification and treatment initiation of those in need of treatment. Moreover, older individuals may benefit from prompt (and possibly early) treatment initiation. This practice is hampered by the incomplete recognition of the burden of disease and management issues in this age group.

In addition to the direct health benefits, appropriate management of HIV among older adults may be associated with economic benefits, either directly through improved labor participation of treated individuals or indirectly through the important contribution older age groups make in caring for children and allowing other family members to work. Indeed, evidence from Kenya suggests that ART's most profound economic impact among younger adults is increased labor participation and the number of hours worked [55]. Another economic benefit of improved treatment of infected older adults is the reduced dependency on younger family members. Dependency ratios, or the ratio of those who are unable to work to those are able to work, are important for a variety of economic growth measures, including saving rates and investments. Declining dependency ratios appear to be a major driver of ‘demographic dividends’, or the economic growth associated with declining fertility and mortality [56]. For example, extending the oldest age of potential labor force participation from approximately 64 to 65 years old in many African countries by treating infected older adults with ART would reduce the old age dependency ratio in eastern and southern African countries by 7–10% [1,57]. In other regions, this reduction was associated with substantial economic growth [56].

Finally, reducing the burden of HIV among the elderly could have other important social and welfare benefits. In regions with high HIV prevalence, the elderly often serve as caretakers for ailing children and often as primary caretakers for their grandchildren [58]. That is, even without direct economic productivity, Africa's elderly play important social roles, and reducing HIV epidemic's burden in this age group could have widespread benefits.

Conclusions and recommendations

We present evidence that suggests older Africans with HIV are, first, a demographically important group; second, epidemiologically substantial; and, third, require targeted policies and interventions. Moreover, targeting this group could be associated with health, economic, and social benefits. However, much remains unknown about the burden of, and unique approaches to, HIV among older Africans.

Better characterization of the disease burden would be foundational to policy making and resource allocation decisions. Some opportunities for improved epidemiologic characterization include expanding DHS serosurveys to include all age groups, especially for HIV testing; including older individuals in recent HIV incidence measurement efforts; and identification of older adults as a unique group in national and United National Programme on AIDS prevalence estimates.

Guideline development processes should also address the unique needs and challenges of HIV in older adults. Unique considerations include different ART initiation efforts that prioritize timely initiation (and possibly earlier initiation thresholds, as recently recommended in the USA); increased awareness of the potential for comorbid disease resulting from HIV itself or ART; and unique guidance on the management of comorbidities that occur with greater frequency in this population.

Finally, prioritizing older adults should be accompanied by operational and resource allocation analyses. Although a case can be made for untapped health, economic, and social benefits associated with prioritizing the care of HIV among older Africans, the value of these benefits should be considered in the context of the limited resources. As the continued global economic woes continue to threaten the available resources available for the prevention and treatment of HIV in many African countries, identifying and prioritizing the areas of greatest societal value will become increasingly important.

Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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Keywords:

aging; antiretroviral access; co-morbidities; elderly; polypill

© 2012 Lippincott Williams & Wilkins, Inc.