The December 1st issue of Clinical Infectious Diseases contains a raft of papers addressing the issue of HIV and aging (abstracts and links below). A report from the Swiss HIV Cohort Study documents that illnesses typically associated with aging are now the most common causes of morbidity in their cohort, which contains an increasing proportion of individuals aged 50 or older (see graph). In contrast, opportunistic infections make only a minor contribution in the current era of effective antiretroviral therapy (ART). An accompanying editorial by Mike Saag highlights the implications for providing appropriate multidisciplinary care to people with HIV as they age.
Age distribution among active participants of the Swiss HIV Cohort Study over time. Hasse B et al. Clin Infect Dis. 2011;53:1130-1139. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
While there are ongoing debates about whether HIV infection is linked to premature aging—some studies have suggested the risk of aging-associated diseases is increased among HIV-positive people compared to age-matched HIV-negative individuals, while other studies have disputed these findings—the Swiss HIV Cohort Study paper emphasizes that whether or not they are occurring sooner, these morbidities are now the main concern in the long-term care of people with HIV. In discussing their findings, the authors note that the incidence of cancer, heart attacks and diabetes among members of their cohort aged 50-64 was higher than described in studies of somewhat comparable HIV-negative cohorts, but they also stress that "a comparison of our results with an age-matched HIV-uninfected population with similar comorbidity or behavior is difficult, because we had no suitable HIV-uninfected control group in our country."
Giovanni Guaraldi and colleagues from the University of Modena and Reggio Emilia in Italy attempted to address this issue in their study, which compared the occurrence of non-infectious co-morbidities (NICMs) and polypathology (the presence of more than one NICM) among HIV-positive people on ART and a matched HIV-negative control group from the general population (from 2002 through 2009). The NICMs captured in the study included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. The results revealed that prevalence of NICMs and polypathology was higher in HIV-positive individuals across all age categories. The prevalence of polypathology among people with HIV aged 41-50 was similar to the prevalence among HIV-negative controls aged 51-60.
Interpretation of the findings is complicated by the fact that the data from HIV-positive individuals was all derived from a metabolic clinic at Modena. Part of this population is comprised of local people from main HIV clinic at Modena who are automatically referred to the metabolic clinic if they are on ART. However, the population also includes a large proportion of HIV-positive individuals who are referred to the Modena metabolic clinic from neighboring centers due to metabolic issues such as lipodystrophy, and this would appear to account for the unusually high prevalence of this condition among the study cohort (74%). To assess whether this over-representation of people with metabolic issues had biased their results, the study authors compared the incidence of NICMs and polypathology among the local referrals to those from the neighboring centers but—perhaps surprisingly, as Jacqueline Capeau notes in an accompanying editorial commentary—they found no difference.
The authors conclude: "our findings suggest that an aggressive approach to the screening, diagnosis, and treatment of NICMs is warranted as part of routine healthcare for HIV-infected patients. Furthermore, our data suggest that onset of such screening should commence at a substantially earlier age for HIV-infected persons, compared with HIV-uninfected persons, possibly at least a decade in advance. Additional studies are needed to further evaluate the impact of convergent age-related NICMs on age-related functional status, frailty, and disability among ART-experienced HIV-infected persons and to provide insights into accelerated aging processes that may be associated with chronic HIV infection."
The last paper of the raft describes a population-based study carried out in Denmark to assess the risk of cataract surgery among HIV-positive individuals compared to large group of matched HIV-negative controls. Risk was found to be greater among the HIV-positive population, with the highest risk among those with CD4 T cell counts below 200 (either on or off ART). Individuals on ART with CD4 T cell counts over 200 still showed a higher risk than both the general population and HIV-positive people with over 200 CD4 T cells who had not yet started ART; the authors note this could reflect a contribution of drug side effects or receipt of ART could be acting as a marker for having reached a stage of illness requiring treatment (which in turn is associated with an elevated cataract risk). Supporting the latter possibility, no association with specific antiretroviral drugs was found. Although the researchers do not claim that their data represents evidence of accelerated aging in the HIV-positive population, they acknowledge that such a phenomenon “cannot be excluded as a possible part of the explanation.”
Clin Infect Dis. 2011 Oct 13. [Epub ahead of print]
Morbidity and Aging in HIV-Infected Persons: The Swiss HIV Cohort Study.
Hasse B, Ledergerber B, Furrer H, Battegay M, Hirschel B, Cavassini M, Bertisch B, Bernasconi E, Weber R; the Swiss HIV Cohort Study.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and University of Zurich.
Abstract
Background. Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study.
Methods. The Swiss HIV Cohort Study is a prospective observational cohort established in 1988 with continuous enrollment. We determined the incidence of clinical events (per 1000 person-years) from January 2008 (when a new questionnaire on non-AIDS-related morbidity was introduced) through December 2010. Differences across age groups were analyzed using Cox regression, adjusted for CD4 cell count, viral load, sex, injection drug use, smoking, and years of HIV infection.
Results. Overall, 8444 (96%) of 8848 participants contributed data from 40 720 semiannual visits; 2233 individuals (26.4%) were aged 50-64 years, and 450 (5.3%) were aged ≥65 years. The median duration of HIV infection was 15.4 years (95% confidence interval [CI], 9.59-22.0 years); 23.2% had prior clinical AIDS. We observed 994 incident non-AIDS events in the reference period: 201 cases of bacterial pneumonia, 55 myocardial infarctions, 39 strokes, 70 cases of diabetes mellitus, 123 trauma-associated fractures, 37 fractures without adequate trauma, and 115 non-AIDS malignancies. Multivariable hazard ratios for stroke (17.7; CI, 7.06-44.5), myocardial infarction (5.89; 95% CI, 2.17-16.0), diabetes mellitus (3.75; 95% CI, 1.80-7.85), bone fractures without adequate trauma (10.5; 95% CI, 3.58-30.5), osteoporosis (9.13; 95% CI, 4.10-20.3), and non-AIDS-defining malignancies (6.88; 95% CI, 3.89-12.2) were elevated for persons aged ≥65 years.
Conclusions. Comorbidity and multimorbidity because of non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS-defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increase with older age.
Clin Infect Dis. 2011 Oct 13. [Epub ahead of print]
EDITORIAL COMMENTARY: HIV Now Firmly Established in the Middle Ages.
Saag MS.
Source
Center for AIDS Research, University of Alabama at Birmingham.
Clin Infect Dis. 2011 Oct 13. [Epub ahead of print]
Premature Age-Related Comorbidities Among HIV-Infected Persons Compared With the General Population.
Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, Berti A, Rossi E, Roverato A, Palella F.
Department of Medicine and Medical Specialities, University of Modena and Reggio Emilia.
Abstract
Background. Human immunodeficiency virus (HIV)-infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population. We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects.
Methods. We performed a case-control study involving antiretroviral therapy (ART)-experienced HIV-infected patients treated at Modena University, Italy, from 2002 through 2009. These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp) was defined as the concurrent presence of ≥2 NICMs. Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp.
Results. There were 2854 patients and 8562 control subjects. The mean age was 46 years, and 37% were women. Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P <.001). Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension. Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P < .001) age (odds ratio [OR], 1.11), male sex (OR, 1.77), nadir CD4 cell count <200 cells/μL (OR, 4.46), and ART exposure (OR, 1.01).
Conclusions. Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population. The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors. These data support the need for earlier screening for NICMs in HIV-infected patients.
Clin Infect Dis. 2011 Oct 13. [Epub ahead of print]
Capeau J.
UPMC Univ Paris 06, UMR_S938, Inserm, CDR Saint-Antoine, F-75012 and AP-HP, Hôpital Tenon, F-75020, Paris, France.
Clin Infect Dis. 2011 Oct 13. [Epub ahead of print]
Rasmussen LD, Kessel L, Molander LD, Pedersen C, Gerstoft J, Kronborg G, Obel N.
Department of Infectious Diseases, Odense University Hospital.
Abstract
Background. Premature aging has been suggested a risk factor for early death in patients infected with human immunodeficiency virus (HIV). Therefore, the risk of age-related diseases, such as cataracts, should be increased in this population. In a nationwide, population-based cohort study we assessed the risk of cataract surgery in HIV-infected individuals compared with the general population.
Methods. We identified 5315 HIV-infected individuals from a Danish national cohort of HIV-infected individuals and a population-based age- and sex-matched comparison cohort of 53 150 individuals. Data on cataract surgery were obtained from the Danish National Hospital registry. Cumulative incidence curves were constructed. Incidence rate ratios (IRRs) and impact of immunodeficiency, highly active antiretroviral therapy (HAART), and treatment with abacavir, tenofovir, protease inhibitors, and nonnucleoside analogue reverse-transcriptase inhibitors (NNRTIs) were estimated by Poisson regression analyses and adjusted for age, sex, and calendar year.
Results. HIV-infected individuals had a higher risk of cataract surgery than the comparison cohort (adjusted IRR, 1.87; 95% confidence interval (CI): 1.50-2.33). The highest risk was found in patients with a CD4 cell count ≤200 cells/μL (adjusted IRR before HAART initiation, 3.11 [95% CI, 1.26-7.63]; adjusted IRR after HAART initiation, 4.74 [95% CI, 2.60-8.62]). In patients not receiving HAART and those receiving HAART with a CD4 cell count >200 cells/mL the adjusted IRRs were 0.60 (95% CI: 0.22-1.61) and 1.87 (95% CI: 1.46-2.39). Treatment with abacavir, tenofovir, protease inhibitors, or NNRTIs did not increase the risk substantially.
Conclusions. HIV-infected individuals have an increased risk of cataract surgery. The risk is mainly associated with immunodeficiency and HAART, but accelerated aging cannot be excluded as part of the possible explanation.
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