When to Initiate Antiretroviral Therapy in HIV and Aging (Updated 6/5/17)

For older HIV-infected patients, antiretroviral therapy is recommended for all, regardless of CD4 cell count.

  • Antiretroviral therapy is extremely important for older HIV-infected patients as these individuals have a greater risk of developing serious non-AIDS complications.
  • Antiretroviral therapy should be initiated as early as possible in older patients due to the frequent blunted immune response and relatively poor CD4 cell increases in response to antiretroviral therapy.
  • Clinicians should not withhold therapy in older patients due to concerns for poor virologic responses to therapy as available data suggest older patients have high virologic response rates.
  • Older patients on antiretroviral therapy should receive close monitoring for adverse drug effects related to antiretroviral therapy.

Multiple cohort studies involving untreated HIV-infected persons have established that older persons have a more rapid progression to AIDS and shortened survival when compared with younger persons [1-4]. For HIV-infected persons older than 50, limited data exist from randomized, controlled antiretroviral therapy clinical trials, as most randomized therapy trials have excluded persons older than 50 or 60. A retrospective analysis of 253 patients 50 years of age or older found antiretroviral therapy substantially improved survival rates [5]. Several large retrospective studies have clearly shown delayed and diminished CD4 cell recovery after starting antiretroviral therapy in older HIV-infected patients when compared with younger age groups[6-9]. Studies have shown conflicting results with respect to virologic responses in older versus younger [10-13], with the most comprehensive study showing high virologic response rates [14] and no significant difference in virologic responses based in older versus younger adults [8] .

The major antiretroviral therapy guidelines that most influences clinical practice in the United States—the Department of Health and Human Services (DHHS) Panel guidelines [15]—recommends initiating antiretroviral therapy in all persons infected with HIV.  The recommendation to use antiretroviral therapy in all HIV-infected persons is based on reducing the risk of disease progression and decreasing the risk of HIV transmission. Data from several large cohort studies have strongly suggested a survival advantage with initiation of antiretroviral therapy earlier in the course of HIV disease [16, 17]. In addition, growing evidence suggests that uncontrolled HIV infection produces a “chronic inflammatory state” associated with an increased risk of developing cardiovascular disease [18] and non-AIDS malignancies  [19], and CD4 counts below 500 are associated with higher cardiovascular risk [20], and risk for non-AIDS malignancies [21]. Further, in a large cohort study, investigators reported 10-year mortality in persons 45 to 65 years of age was lower when antiretroviral therapy was initiated at a CD4 threshold of 500 cells/mm3 than delaying to a threshold of 350 cells/mm3  [22].  The rationale for recommending antiretroviral therapy for the prevention of HIV transmission is based on several recent studies, most notably the landmark HPTN 052 trial that showed a greater than 95% reduction in HIV transmission in HIV serodiscordant couples when the HIV-infected partner received antiretroviral therapy [23].

The January 2016 DHHS Antiretroviral Therapy guidelines specifically addressed the use of antiretroviral therapy for persons 50 and older, recommending initiating antiretroviral therapy in all persons older than 50 years of age regardless of CD4 cell count, primarily because, when compared with younger patients, these older HIV-infected individuals have increased risk for non-AIDS related complications and they have diminished CD4 cell count recovery in response to antiretroviral therapy [15].  Further, the DHHS guidelines emphasized that older individuals potentially have increased risk for HIV transmission or acquisition, for several reasons, including (1) alterations reduced mucosal and immunologic defenses may occur with post-menopausal atrophic vaginitis, (2) older individuals have less incentive to use of condoms given the lack of need for pregnancy prevention, and (3) persons older than 50 have lower frequency of HIV screening given their perceived low risk for HIV infection  [24].

The use of antiretroviral therapy in older HIV-infected patients presents several challenges, predominantly due to the increased prevalence of non-HIV-related comorbid medical conditions, such as hyperlipidemia, hypertension, diabetes, and coronary artery disease [25]. In addition, older patients may have age- related changes in body composition that can alter medication volume of distribution and influence drug pharmacokinetics. Compared with younger patients, older patients are more likely to be taking multiple medications not related to HIV and thus increasing the likelihood for drug-drug interactions. Further, several studies have shown older HIV- infected patients have increased risk for developing drug-related toxicity, including hyperglycemia, elevated creatinine, and unfavorable alterations in lipid profile [7].

Updated by David Spach, MD



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