Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV
Considerations for Antiretroviral Use in Special Patient Populations
HIV and the Older Patient
Last Updated: January 28, 2016; Last Reviewed: January 28, 2016
|Key Considerations When Caring for Older Patients With HIV|
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = Data from randomized controlled trials; II = Data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion
Effective antiretroviral therapy (ART) has increased survival in individuals with HIV, resulting in an increasing number of older individuals living with HIV. In the United States, among persons living with HIV at year-end 2013, 42% were age 50 years or older, 6% were age 65 or older, and trends suggest that these proportions will increase steadily.1 Care of patients with HIV increasingly will involve adults 60 to 80 years of age, a population for which data from clinical trials or pharmacokinetic (PK) studies are very limited.
There are several distinct areas of concern regarding the association between age and HIV disease.2 First, older patients with HIV may suffer from aging-related comorbid illnesses that can complicate the management of HIV infection. Second, HIV disease may affect the biology of aging, possibly resulting in early manifestations of clinical syndromes generally associated with advanced age. Third, reduced mucosal and immunologic defenses (such as postmenopausal atrophic vaginitis) and changes in risk related-behaviors (e.g., decrease in condom use because of less concern about pregnancy or more high-risk sexual activity with increased use of erectile dysfunction drugs) in older adults could lead to increased risk of acquisition and transmission of HIV.3,4 Finally, because older adults are generally perceived to be at low risk of acquiring HIV, screening for this population remains low.
HIV Diagnosis and Prevention in the Older Adult
In older adults, failure to consider a diagnosis of HIV likely contributes to later initiation of ART.5 The Centers for Disease Control and Prevention (CDC) estimates that in 2013, 37% of adults aged 55 years or older at the time of HIV diagnosis met the case definition for AIDS. The comparable CDC estimates are 18% for adults aged 25 to 34 years and 30% for adults aged 35 to 44 years.6 In one observational cohort, older patients (defined as those ≥35 years of age) appeared to have lower CD4 T lymphocyte (CD4) cell counts at seroconversion, steeper CD4 count decline over time,7 and tended to present to care with significantly lower CD4 counts.8 When individuals >50 years of age present with severe illnesses, AIDS-related opportunistic infections (OIs) need to be considered in the differential diagnosis of the illness.
Although many older individuals engage in risk behaviors associated with acquisition of HIV, they may see themselves or be perceived by providers as at low risk of infection and, as a result, they are less likely to be tested for HIV infection than younger persons.9,10 Despite CDC guidelines recommending HIV testing at least once in individuals aged 13 to 64, and more frequently for those at risk,11 HIV testing prevalence remains low (<5%) among adults aged 50 to 64, and decreased with increasing age.12 Clinicians must be attuned to the possibility of HIV infection in older adults, including those older than 64 years of age and especially in those who may engage in high-risk behaviors. Sexual history taking is therefore an important component of general health care for older adults who do not have HIV, together with risk-reduction counseling, and screening for HIV and sexually transmitted infections (STIs), if indicated.
Impact of Age on HIV Disease Progression
HIV infection presents unique challenges in aging adults and these challenges may be compounded by ART:
- HIV infection itself is thought to induce immune-phenotypic changes akin to accelerated aging,13 but recent laboratory and clinical data provide a more nuanced view of these changes. Some studies have shown that patients with HIV may exhibit chromosomal and immunologic features similar to those induced by aging.14,15 However, other studies show the immunologic changes to be distinct from age-related changes.16 In addition, although data on the increased incidence and prevalence of age-associated comorbidities in patients with HIV are accumulating,17,18 the age of diagnosis for myocardial infection and non-AIDS cancers in patients who have HIV and those who do not is the same.18,19
- Older patients with HIV have a greater incidence of complications and comorbidities than adults of a similar age who do not have HIV, and may exhibit a frailty phenotype—defined clinically as a decrease in muscle mass, weight, physical strength, energy, and physical activity,20 although the phenotype is still incompletely characterized in people with HIV.
Initiating Antiretroviral Therapy in the Older Patient with HIV
ART is recommended for all individuals with HIV (AI; see Initiation of Antiretroviral Therapy section). Early treatment may be particularly important in older adults in part because of decreased immune recovery and increased risk of serious non-AIDS events in this population. In a modeling study based on data from an observational cohort, the beneficial effects of early ART were projected to be greatest in the oldest age group (patients between ages 45 and 65 years).21 No data support a preference for any one of the Panel’s recommended initial ART regimens (see What to Start) on the basis of patient age. The choice of regimen should instead be informed by a comprehensive review of the patient’s other medical conditions and medications. The What to Start section (Table 7) of these guidelines provides guidance on selecting an antiretroviral regimen based on an older patient’s characteristics and specific clinical conditions (e.g., kidney disease, elevated risk for cardiovascular disease, osteoporosis). In older patients with reduced renal function, dosage adjustment of nucleoside reverse transcriptase inhibitors (NRTIs) may be necessary (see Appendix B, Table 7). In addition, ARV regimen selection may be influenced by potential interaction of antiretroviral medications with drugs used concomitantly to manage comorbidities (see Tables 18a-19b). Adults age >50 years should be monitored for ART effectiveness and safety similarly to other populations with HIV (see Table 3); however, in older patients, special attention should be paid to the greater potential for adverse effects of ART on renal, liver, cardiovascular, metabolic, and bone health (see Table 14).
HIV, Aging, and Antiretroviral Therapy
The efficacy, PKs, adverse effects, and drug interaction potentials of ART in the older adult have not been studied systematically. There is no evidence that the virologic response to ART differs in older and younger patients. In a recent observational study, a higher rate of viral suppression was seen in patients >55 years old than in younger patients.22 However, ART-associated CD4 cell recovery in older patients is generally slower and lower in magnitude than in younger patients.8,23-25 This observation suggests that starting ART at a younger age may result in better immunologic response and possibly clinical outcomes.
Hepatic metabolism and renal elimination are the major routes of drug clearance, including the clearance of ARV drugs. Both liver and kidney functions decrease with age and may result in impaired drug elimination and increased drug exposure.26 Most clinical trials have included only a small proportion of participants over 50 years of age, and current ARV dosing recommendations are based on PK and pharmacodynamic data derived from participants with normal organ function. Whether drug accumulation in the older patient may lead to greater incidence and severity of adverse effects than seen in younger patients is unknown.
Patients with HIV and aging-associated comorbidities may require additional pharmacologic interventions that can complicate therapeutic management. In addition to taking medications to manage HIV infection and comorbid conditions, many older patients with HIV also are taking medications to relieve discomfort (e.g., pain medications, sedatives) or to manage adverse effects of medications (e.g., anti-emetics). They also may self-medicate with over-the-counter medicines or supplements. In older patients who do not have HIV, polypharmacy is a major cause of iatrogenic complications.27 Some of these complications may be caused by medication errors (by prescribers or patients), medication nonadherence, additive drug toxicities, and drug-drug interactions. Older patients with HIV are probably at an even greater risk of polypharmacy-related adverse consequences than younger or similarly aged patients with HIV. When evaluating any new clinical complaint or laboratory abnormality in patients with HIV, especially in older patients, clinicians should always consider the possible role of adverse drug reactions from both ARV drugs and other concomitantly administered medications.
Drug-drug interactions are common with ART and can be easily overlooked by prescribers.28 The available drug interaction information on ARV agents is derived primarily from PK studies performed in small numbers of relatively young participants with normal organ function who do not have HIV (see Tables 18a-19b). Data from these studies provide clinicians with a basis to assess whether a significant interaction may exist. However, the magnitude of the interaction may be greater in older patients with HIV than in younger patients with HIV.
Nonadherence is the most common cause of treatment failure. Complex dosing requirements, high pill burden, inability to access medications because of cost or availability, limited health literacy including misunderstanding of instructions, depression, and neurocognitive impairment are among the key reasons for nonadherence.32 Although many of these factors associated with nonadherence may be more prevalent in older patients, some studies have shown that older patients with HIV may actually be more adherent to ART than younger patients.29-31 Clinicians should regularly assess older patients to identify any factors, such as neurocognitive deficits, that may decrease adherence. To facilitate medication adherence, it may be useful to discontinue unnecessary medications, simplify regimens, and recommend evidence-based behavioral approaches including the use of adherence aids such as pillboxes or daily calendars, and support from family members (see Adherence to the Continuum of Care).
Non-AIDS HIV-Related Complications and Other Comorbidities
Among persons treated effectively with ART, as AIDS-related morbidity and mortality have decreased, non-AIDS conditions constitute an increasing proportion of serious illnesses.33-35 Neurocognitive impairment, already a major health problem in aging adults, may be exacerbated by the effect of HIV infection on the brain.36 In a prospective observational study, neurocognitive impairment was predictive of lower retention in care among older persons.37 Neurocognitive impairment probably also affects adherence to therapy. Social isolation and depression are also particularly common among older adults with HIV and, in addition to their direct effects on morbidity and mortality, may contribute to poor medication adherence and retention in care.38,39 Heart disease and cancer are the leading causes of death in older Americans.40 Similarly, non-AIDS events such as heart disease, liver disease, and cancer have emerged as major causes of morbidity and mortality in patients with HIV receiving effective ART. The presence of multiple non-AIDS comorbidities coupled with the immunologic effects of HIV infection may add to the disease burden of aging adults with HIV.41-43 HIV-specific primary care guidelines have been updated with recommendations for lipid and glucose monitoring, evaluation and management of bone health, and management of kidney disease, and are available for clinicians caring for older patients with HIV.44-48
Switching, Interrupting, and Discontinuing Antiretroviral Therapy in Older Patients
Given the greater incidence of comorbidities, non-AIDS complications and frailty among older patients with HIV, switching one or more ARVs in an HIV regimen may be necessary to minimize toxicities and drug-drug interactions. For example, expert guidance now recommends bone density monitoring in men aged ≥50 years and postmenopausal women, and suggests switching from tenofovir disoproxil fumarate or boosted protease inhibitors to other ARVs in older patients at high risk for fragility fractures.45
Few data exist on the use of ART in severely debilitated patients with chronic, severe, or non-AIDS terminal conditions.49,50 Withdrawal of ART usually results in rebound viremia and a decline in CD4 cell count. Acute retroviral syndrome after abrupt discontinuation of ART has been reported. In severely debilitated patients, if there are no significant adverse reactions to ART, most clinicians would continue therapy. In cases where ART negatively affects quality of life, the decision to continue therapy should be made together with the patient and/or family members after a discussion on the risks and benefits of continuing or withdrawing ART.
Healthcare Utilization, Cost Sharing, and End-of-Life Issues
Important issues to discuss with aging patients with HIV are living wills, advance directives, and long-term care planning, including related financial concerns. Out-of-pocket health care expenses (e.g., copayments, deductibles), loss of employment, and other financial-related factors can cause temporary interruptions in treatment, including ART, which should be avoided whenever possible. The increased life expectancy and the higher prevalence of chronic complications in aging populations with HIV can place greater demands upon HIV services.51 Facilitating a patient’s continued access to insurance can minimize treatment interruptions and reduce the need for other services to manage concomitant chronic disorders.
HIV disease can be overlooked in aging adults who tend to present with more advanced disease and experience accelerated CD4 loss. HIV induces immune-phenotypic changes that have been compared to accelerated aging. Effective ART has prolonged the life expectancy of patients with HIV, increasing the number of patients >50 years of age living with HIV. However, unique challenges in this population include greater incidence of complications and comorbidities, and some of these complications may be exacerbated or accelerated by long term use of some ARV drugs. Providing comprehensive multidisciplinary medical and psychosocial support to patients and their families (the “Medical Home” concept) is of paramount importance in the aging population. Continued involvement of HIV experts, geriatricians, and other specialists in the care of older patients with HIV is warranted.
- Centers for Disease Control and Prevention. HIV Surveillance Report, 2014; vol. 26. 2015. Available at http://www.cdc.gov/hiv/library/reports/surveillance/. Accessed December 10, 2015.
- Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ. 2009;338:a3172. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19171560.
- Levy JA, Ory MG, Crystal S. HIV/AIDS interventions for midlife and older adults: current status and challenges. J Acquir Immune Defic Syndr. Jun 1 2003;33 Suppl 2:S59-67. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12853854.
- Levy BR, Ding L, Lakra D, Kosteas J, Niccolai L. Older persons' exclusion from sexually transmitted disease risk-reduction clinical trials. Sex Transm Dis. Aug 2007;34(8):541-544. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17297381.
- Althoff KN, Gebo KA, Gange SJ, et al. CD4 count at presentation for HIV care in the United States and Canada: are those over 50 years more likely to have a delayed presentation? AIDS Res Ther. 2010;7:45. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21159161.
- Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 U.S. dependent areas—2013. HIV Surveillance Supplemental Report 2015;20 (No. 2). 2015. Available at: http://www.cdc.gov/hiv/library/reports/surveillance/. Accessed August 21, 2015.
- Lodi S, Phillips A, Touloumi G, et al. Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count thresholds <200, <350, and <500 Cells/mm3: assessment of need following changes in treatment guidelines. Clin Infect Dis. Oct 2011;53(8):817-825. Available at http://www.ncbi.nlm.nih.gov/pubmed/21921225.
- Sabin CA, Smith CJ, d'Arminio Monforte A, et al. Response to combination antiretroviral therapy: variation by age. AIDS. Jul 31 2008;22(12):1463-1473. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18614870.
- Stone VE, Bounds BC, Muse VV, Ferry JA. Case records of the Massachusetts General Hospital. Case 29-2009. An 81-year-old man with weight loss, odynophagia, and failure to thrive. N Engl J Med. Sep 17 2009;361(12):1189-1198. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19759382.
- Ward EG, Disch WB, Schensul JJ, Levy JA. Understanding low-income, minority older adult self-perceptions of HIV risk. J Assoc Nurses AIDS Care. Jan-Feb 2011;22(1):26-37. Available at http://www.ncbi.nlm.nih.gov/pubmed/20580270.
- Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. Sep 22 2006;55(RR-14):1-17. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16988643.
- 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. Aug 2015;42(8):405-410. Available at http://www.ncbi.nlm.nih.gov/pubmed/26165428.
- Martin J, Volberding P. HIV and premature aging: A field still in its infancy. Ann Intern Med. Oct 5 2010;153(7):477-479. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20921548.
- Liu JC, Leung JM, Ngan DA, et al. Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease. PLoS One. 2015;10(4):e0124426. Available at http://www.ncbi.nlm.nih.gov/pubmed/25885433.
- Zanet DL, Thorne A, Singer J, et al. Association between short leukocyte telomere length and HIV infection in a cohort study: No evidence of a relationship with antiretroviral therapy. Clin Infect Dis. May 2014;58(9):1322-1332. Available at http://www.ncbi.nlm.nih.gov/pubmed/24457340.
- Lee FJ, Amin J, Carr A. Efficacy of initial antiretroviral therapy for HIV-1 infection in adults: a systematic review and meta-analysis of 114 studies with up to 144 weeks' follow-up. PLoS One. 2014;9(5):e97482. Available at http://www.ncbi.nlm.nih.gov/pubmed/24830290.
- Schouten J, Wit FW, Stolte IG, et al. Cross-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. Dec 15 2014;59(12):1787-1797. Available at http://www.ncbi.nlm.nih.gov/pubmed/25182245.
- Althoff KN, McGinnis KA, Wyatt CM, et al. 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. Feb 15 2015;60(4):627-638. Available at http://www.ncbi.nlm.nih.gov/pubmed/25362204.
- Rasmussen LD, May MT, Kronborg G, et al. Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study. Lancet HIV. Jul 2015;2(7):e288-298. Available at http://www.ncbi.nlm.nih.gov/pubmed/26423253.
- Althoff KN, Jacobson LP, Cranston RD, et al. Age, comorbidities, and AIDS predict a frailty phenotype in men who have sex with men. J Gerontol A Biol Sci Med Sci. Feb 2014;69(2):189-198. Available at http://www.ncbi.nlm.nih.gov/pubmed/24127428.
- Edwards JK, Cole SR, Westreich D, et al. Age at Entry Into Care, Timing of Antiretroviral Therapy Initiation, and 10-Year Mortality Among HIV-Seropositive Adults in the United States. Clin Infect Dis. Oct 1 2015;61(7):1189-1195. Available at http://www.ncbi.nlm.nih.gov/pubmed/26082505.
- Horberg MA, Hurley LB, Klein DB, et al. The HIV Care Cascade Measured Over Time and by Age, Sex, and Race in a Large National Integrated Care System. AIDS Patient Care STDS. Nov 2015;29(11):582-590. Available at http://www.ncbi.nlm.nih.gov/pubmed/26505968.
- Althoff KN, Justice AC, Gange SJ, et al. Virologic and immunologic response to HAART, by age and regimen class. AIDS. Oct 23 2010;24(16):2469-2479. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20829678.
- Bosch RJ, Bennett K, Collier AC, Zackin R, Benson CA. Pretreatment factors associated with 3-year (144-week) virologic and immunologic responses to potent antiretroviral therapy. J Acquir Immune Defic Syndr. Mar 1 2007;44(3):268-277. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17146370.
- Nogueras M, Navarro G, Anton E, et al. Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more. BMC Infect Dis. 2006;6:159. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17087819.
- Sitar DS. Aging issues in drug disposition and efficacy. Proc West Pharmacol Soc. 2007;50:16-20. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18605223.
- Steinman MA, Hanlon JT. Managing medications in clinically complex elders: "There's got to be a happy medium." JAMA. Oct 13 2010;304(14):1592-1601. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20940385.
- Marzolini C, Back D, Weber R, et al. Ageing with HIV: medication use and risk for potential drug-drug interactions. J Antimicrob Chemother. Sep 2011;66(9):2107-2111. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21680580.
- Wellons MF, Sanders L, Edwards LJ, Bartlett JA, Heald AE, Schmader KE. HIV infection: treatment outcomes in older and younger adults. J Am Geriatr Soc. Apr 2002;50(4):603-607. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11982658.
- Wutoh AK, Elekwachi O, Clarke-Tasker V, Daftary M, Powell NJ, Campusano G. Assessment and predictors of antiretroviral adherence in older HIV-infected patients. J Acquir Immune Defic Syndr. Jun 1 2003;33 Suppl 2:S106-114. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12853859.
- Silverberg MJ, Leyden W, Horberg MA, DeLorenze GN, Klein D, Quesenberry CP, Jr. Older age and the response to and tolerability of antiretroviral therapy. Arch Intern Med. Apr 9 2007;167(7):684-691. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17420427.
- Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly: looking beyond cost and regimen complexity. Am J Geriatr Pharmacother. Feb 2011;9(1):11-23. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21459305.
- Justice AC. HIV and aging: time for a new paradigm. Curr HIV/AIDS Rep. May 2010;7(2):69-76. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20425560.
- Palella FJ, Jr., Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. Sep 2006;43(1):27-34. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16878047.
- Smit C, Geskus R, Walker S, et al. Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion. AIDS. Mar 21 2006;20(5):741-749. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16514305.
- Vance DE, Wadley VG, Crowe MG, Raper JL, Ball KK. Cognitive and everyday functioning in older and younger adults with and without HIV. Clinical Gerontologists. 2011;34(5):413-426. Available at http://www.ncbi.nlm.nih.gov/pubmed/22563140.
- Jacks A, Wainwright DA, Salazar L, et al. Neurocognitive deficits increase risk of poor retention in care among older adults with newly diagnosed HIV infection. AIDS. Aug 24 2015;29(13):1711-1714. Available at http://www.ncbi.nlm.nih.gov/pubmed/26372282.
- Grov C, Golub SA, Parsons JT, Brennan M, Karpiak SE. Loneliness and HIV-related stigma explain depression among older HIV-positive adults. AIDS Care. May 2010;22(5):630-639. Available at http://www.ncbi.nlm.nih.gov/pubmed/20401765.
- Kalichman SC, Heckman T, Kochman A, Sikkema K, Bergholte J. Depression and thoughts of suicide among middle-aged and older persons living with HIV-AIDS. Psychiatr Serv. Jul 2000;51(7):903-907. Available at http://www.ncbi.nlm.nih.gov/pubmed/10875956.
- Kochanek KD, Xu J, Murphy SL, Minino AM, King HC. Deaths: Preliminary data for 2009. National Vital Statistics Reports. 2011;59(4):1-54. Available at https://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_04.pdf.
- Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. Dec 2011;53(11):1120-1126. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21998278.
- Capeau J. Premature Aging and Premature Age-Related Comorbidities in HIV-Infected Patients: Facts and Hypotheses. Clin Infect Dis. Dec 2011;53(11):1127-1129. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21998279.
- Hasse B, Ledergerber B, Furrer H, et al. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis. Dec 2011;53(11):1130-1139. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21998280.
- Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA. 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. Jan 2014;58(1):e1-34. Available at http://www.ncbi.nlm.nih.gov/pubmed/24235263.
- Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis. Apr 15 2015;60(8):1242-1251. Available at http://www.ncbi.nlm.nih.gov/pubmed/25609682.
- Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. Nov 1 2014;59(9):e96-138. Available at http://www.ncbi.nlm.nih.gov/pubmed/25234519.
- American Academy of HIV Medicine. The HIV and Aging Consensus Project: Recommended treatment strategies for clinicians managing older patients with HIV. 2011. Available at http://www.aahivm.org/Upload_Module/upload/HIV%20and%20Aging/Aging%20report%20working%20document%20FINAL.pdf. Accessed January 13, 2016.
- Jacobson TA, Maki KC, Orringer CE, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015.
- Selwyn PA. Chapter 75. In: Berger AM S, JL, Von Roenn JH, ed. Palliative care in HIV/AIDS. In Principles and Practice of Palliative Care and Supportive Oncology 3rd Edition. Philadelphia, PA: Lippincott Williams and Wilkins; 2007:833-848.
- Harding R, Simms V, Krakauer E, et al. Quality HIV Care to the End of life. Clin Infect Dis. Feb 15 2011;52(4):553-554; author reply 554. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21258107.
- Brennan A, Morley D, O'Leary AC, Bergin CJ, Horgan M. Determinants of HIV outpatient service utilization: a systematic review. AIDS Behav. Jan 2015;19(1):104-119. Available at http://www.ncbi.nlm.nih.gov/pubmed/24907780.