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’.
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.
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].
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.
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].
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].
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.
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.
Conflicts of interest
There are no conflicts of interest.