Impact of Changing Demographics of HIV/AIDS on the Role of Primary Care William M. Valenti, MD

In 2005, persons 50 years and older accounted for 24% of persons with HIV infection in the United States-an increase of 7% from the prevalence in 2001.¹ Persons in this age group accounted for 15% of newly diagnosed cases of AIDS in 2005, an increase of 3% from 2001.1 Other changes among persons with HIV infection include the decrease in mortality rates and the causes of death (Table).²

Table

In a study of mortality trends in a cohort of HIV-positive US military beneficiaries, Crum and colleagues2 found a statistically significant increase in non-HIV-related causes of death between the pre-HAART era (8.8% from 1990 to 1996) and the late HAART era (32% from 2000 to 2003). During these time frames, deaths caused by AIDS-defining opportunistic infections and conditions accounted for almost 80% and 56% of deaths, respectively. For example, in New York City, the number of deaths caused by non-HIV-related conditions among HIV-infected persons aged 13 to 64 years increased from 19.8% in 1999 to 26.3% in 2004 (P = .015).³

Sackoff and colleagues³ determined that 75.6% of deaths caused by non-HIV-related conditions could be attributed to substance abuse (31.0%), cardiovascular disease (23.8%), and cancer (20.8%). The findings were similar across black, Hispanic, and white populations. A notable finding was that lung cancer accounted for between 6.0 and 12.6 deaths per 10,000 patients in all racial and ethnic groups.³

Interventions in respect to current epidemiology
Interventions are recommended in 2 broad areas: HIV care and primary and preventive health care. Clinicians who provide HIV care should continue to focus on testing persons aged 13 to 64 years who seek medical attention in primary care, emergency department, and urgent-care settings. ⁴ The aging baby-boomer population and young adults should be tested even if they do not perceive themselves to be at risk for HIV infection; if they are HIV-positive, they can be referred for clinical care promptly.⁴

The CD4+ T-cell count continues to be the strongest predictor of both HIV-related and non-HIV-related deaths.³ Therefore, prompt referral for HIV care is an essential component of universal HIV testing.⁴ Once patients begin an antiretroviral regimen, adherence to treatment is crucial for good outcomes.

Manfredi⁵ probably was the first to report that the life expectancy of HIV-positive persons who receive highly active antiretroviral therapy approximates that of HIV-negative persons. Metabolic complications may be an issue in this population, although some researchers believe that the cause and characteristics of metabolic conditions such as diabetes, hypertension, and hyperlipidemia in the HIV-infected person differ from those associated with metabolic diseases in noninfected persons.^6,7

To reduce the risk of cardiovascular disease in persons with HIV infection, a combination of lifestyle changes and lipid-lowering agents is a priority. Addressing modifiable risk requires special attention but includes the standards established for primary health care, such as encouraging smoking cessation and good dietary and exercise habits. Although the use of lipid-lowering agents may play a role in reducing cardiovascular risk, the activity of such agents in persons with HIV/ AIDS appears to be less predictable than in noninfected persons, highlighting the importance of lifestyle changes.^6,7

How advancing age affects immune system function is a debatable point and the focus of much research. The goals of antiretroviral therapy remain the same regardless of patient age: restoring immune function as measured by increased CD4+ T-cell counts and viral load suppression.

Results from the AIDS Clinical Trial Group (ACTG) 384 study showed that an age of 40 years or younger, female sex, higher baseline viral load, and virological suppression were associated with greater increases in CD4+ T-cell count at 48 weeks of treatment.⁸ When stratified by age, patients who were 40 years and younger had significantly higher CD4+ T-cell counts while receiving treatment than those who were older than 40 years.

A study by Silverberg and colleagues⁹ showed that within 1 year of starting highly active antiretroviral therapy, patients 50 years and older were more likely to achieve an HIV RNA level of fewer than 500 copies/mL after adjusting for comorbidities than those younger than 50 years. These results appeared to be determined more by greater levels of adherence in older patients than immune system function alone. Thus, if immune system reconstitution is better in younger patients than in older patients, this disparity may be overcome by improved adherence in older patients, as suggested by ACTG 384.

Point of care
Who should provide care for persons with HIV infection has been a topic of discussion since the earliest days of the HIV/AIDS epidemic. There is no one correct answer. The best answer is "It depends"-on the patient, the provider's resources and capacity, and access to care.

The ideal care provider is one experienced in HIV medicine who also offers primary care. Collaboration between primary care providers and specialists in HIV medicine is another option. With the new paradigm in which persons with HIV infection live longer and in whom common age-related conditions develop, both primary and specialty care need to be addressed.¹⁰ Regardless of the treatment model, continuity of care and communication among providers are essential.

New epidemiology and therapeutic options
To date, no antiretroviral agent or regimen has been shown to be more effective in older persons than in younger adults, and treatment recommendations are the same for both age groups. However, when choosing an antiretroviral regimen, the clinician needs to consider potential toxicities as well as pill count, convenience, and tolerability. For example, the thymidine analogues zidovudine and stavudine are no longer recommended as first-line therapy in the United States because of their association with mitochondrial toxicity. ¹¹ Instead, other agents, such as tenofovir and abacavir, are now recommended for nucleoside analogue- backbone regimens.

Anecdotally, most providers have developed their own strategies to assess patients for antiretroviral therapy and select regimens based on their experience and preferences. The critical issue is to ensure close follow-up of patients to monitor adverse events and adjust regimens accordingly. Clinical judgment still plays a pivotal role in treatment decisions.

There is no reason to withhold antiretroviral therapy in older patients, especially if they are able to adhere to treatment. The critical issues are proper regimen selection and followup. Furthermore, there are no data on antiretroviral dosing adjustments for older patients. The standard recommendations for selecting antiretroviral agents or making dose adjustments based on renal or hepatic function determine treatment.

There are no guidelines that are age-specific. However, in addition to the guidelines cited above4,10 the Infectious Diseases Society of America (IDSA) has issued 2 worth mentioning: guidelines for the management of lipid disorders and cardiovascular risk in persons with HIV infection who receive antiretrovirals12 and guidelines for the management of chronic kidney disease in HIV-positive patients.¹³

For lipid management, the IDSA recommends that HIV-infected adults should undergo evaluation and treatment on the basis of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III Guidelines.¹⁴ The NCEP recommends that nonpharmacological interventions be given a thorough trial before consideration of drug therapy. The recommendations also stipulate that intensive therapy with lipidlowering medications should be used in persons with metabolic syndrome. This includes aggressive treatment of hypertension, diabetes, and dyslipidemia. The NCEP also emphasizes the importance of smoking cessation, weight reduction, increased physical activity, and a salubrious diet. The fundamental message still is that physicians must treat HIV infection first. The choice of antiretroviral therapy depends on many patient-specific factors, of which cardiovascular risk is only one.

The IDSA renal guidelines are quite specific in terms of their recommendations that all patients at the time of HIV diagnosis be assessed for existing kidney disease with a screening urinalysis for proteinuria and a calculated estimate of renal function (creatinine clearance or glomerular filtration rate).¹³ This renal function estimate also allows the physician to properly prescribe antiretroviral agents and other commonly used medications that require renal adjustment. Therapy for HIVassociated renal disease should be individualized to the patient's clinical circumstances and to the underlying renal histology findings. The guidelines also recommend ongoing evaluation of renal function, for example, measuring baseline renal function with serum creatinine and urinalysis, during antiretroviral therapy.

Conclusion
The epidemiology of HIV/AIDS is changing as patients live longer and are at risk for more common age related comorbidities. In the era before potent antiretroviral therapy was the standard of HIV care, primary care needs were shorter-term because most HIV-positive persons did not live long enough for diabetes or cardiovascular disease to develop. In the current era, these shifts reinforce the important role of primary care in addition to the specialty management of HIV/AIDS.

At minimum, patients with HIV infection need primary and specialty care. There are many options for ensuring that patients have both. The ideal is a seamless model of primary care and HIV/AIDS care by the same providers in the same setting. However, this will not always be possible for many reasons, including patient preference, provider expertise and resources, and reimbursement constraints.

When treatment is divided between a primary care provider and an HIV/AIDS care specialist, both providers need to establish a communication path to share information such as progress notes, medication lists, and reports from consultants and laboratories. This approach can help manage costs, prevent duplication of effort and, most important, contribute to better patient outcomes.

Erratum

An editorial error appeared on page 364 of August issue in the article "Emerging Pathogens and New Recommendations in Travel Medicine." The passage should read:

"Routine adult vaccine guidelines have been updated to include varicella-zoster vaccination of adults 60 years and older who have evidence of past varicella immunity. Evidence of past varicella immunity is described in the 2008 ACIP Adult Immunization Schedule.⁵¹ All adults without evidence of immunity to varicella should receive 2 doses of single-antigen varicella vaccine unless they have a medical contraindication."

Apologies to the authors and readers for this oversight.

In addition, the authors would like to amend the last statement in Table 3 to read as follows:

"Persons who suspect that they were exposed to TB should be advised to seek medical evaluation because treatment for latent disease with isoniazid may be required. Because of the increased incidence of MDR-TB and XDR-TB, those with test conversion or signs and symptoms of TB associated with international travel should seek care from experts in infectious disease or pulmonary medicine."

References:

• Centers for Disease Control and Prevention. HIV/AIDS among persons aged 50 and older. wwwtest.cdc.gov/hiv/topics/over50/ resources/factsheets/pdf/over50.pdf. Accessed July 8, 2008.

• Crum NF, Riffenburgh RH, Wegner S, et al; Triservice AIDS Clinical Consortium. Comparisons of causes of death and mortality rates among HIV-infected persons: analysis of the pre-, early, and late HAART (highly active antiretroviral therapy) eras. J Acquir Immune Defic Syndr. 2006;41:194-200.

• Sackoff JE, Hanna DB, Pfeiffer MR, Torian LV. Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City. Ann Intern Med. 2006;145:397- 406.

• Branson BM, Handsfield HH, Lampe MA, et al; Centers for Disease Control and Prevention. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR. 2006;55 (RR-14):1-17. www.cdc.gov/mmwr/preview/ mmwrhtml/rr5514a1.htm. Accessed July 15, 2008.

• Manfredi R. HIV infection and advanced age: emerging epidemiological, clinical, and management issues. Ageing Res Rev. 2004;3:31-54.

• Grinspoon SK, Grunfeld C, Kotler DP, et al. State of the science conference: initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: executive summary. Circulation. 2008;118:198-210. http://circ.ahajournals.org/cgi/content/ short/CIRCULATIONAHA.107.189622v1? rss=1. Accessed July 15, 2008.

• Joy T, Keogh HM, Hadigan C, et al. Dietary fat intake and relationship to serum lipid levels in HIV-infected patients with metabolic abnormalities in the HAART era. AIDS. 2007;21:1591- 1600.

• Gandhi RT, Spritzler J, Chan E, et al; ACTG 384 Team. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr. 2006;42:426-434.

• Silverberg M, Leyden W, Horberg MA, et al. Older age and the response to and tolerability of antiretroviral therapy. Arch Intern Med. 2007; 167:684-691.

• Aberg JA, Gallant JE, Anderson J, et al; HIV Medicine Association of the Infectious Diseases Society of America. Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2004;39:609-629.

• Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington, DC: Department of Health and Human Services. January 29, 2008; 1-128. www.aidsinfo.nih.gov/ContentFiles/ AdultandAdolescentGL.pdf. Accessed July 8, 2008.

• Dube MP, Stein JH, Aberg JA, et al; Adult AIDS Clinical Trials Group Cardiovascular Subcommittee; HIV Medical Association of the Infectious Diseases of America. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Diseases Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis. 2003;37:613-627.

• Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559-1585.

• Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.