Selection and Initiation of Antiretroviral Treatment
Once patients are diagnosed with HIV infection, initiation of antiretroviral therapy becomes a pressing concern both for the personal benefit of the patient and to prevent any further transmission of the virus. Older individuals experience higher HIV-1 RNA viral loads and a more rapid decline in CD4 cell count prior to treatment and experience delayed diagnosis and treatment compared to younger patients.
All individuals infected with HIV experience dramatic and sustained benefit from lifelong antiretroviral therapy. Standard regimens require multiple medications from multiple medication classes. The most common regimens require at least three daily medications, either a nonnucleoside reverse transcriptase inhibitor or a protease inhibitor and two nucleoside reverse transcriptase inhibitors. New classes are recently available and others are under development. Many patients in the United States now take a single coformulated tablet once a day. These newer medications have reduced adverse effects and increased rates of successful viral suppression. They also appear to be more tolerate of minor variations in adherence. In many settings 80% to 90% of those newly initiating ART achieve suppression of the HIV-1 RNA to below 50 copies/mL. and most are able to sustain this level of suppression for many years. There is a growing consensus that treatment should begin immediately after diagnosis, regardless of CD4 cell count. This strategy is likely cost effective as it minimizes risk of HIV transmission, AIDS defining illnesses, and later emergence of HIV-associated non-AIDS conditions.
There are now many antiretrovirals from which to choose and this selection should be informed by consultation with an experienced HIV care provider in light of an HIV-1 RNA viral resistance profile and careful consideration of preexisting organ system injury, mental illness, or, in the case of abacavir, genetic susceptibility to toxicity. Patients require close follow-up for the first several months of therapy to ensure that HIV-1 RNA suppression is achieved and that no concerning adverse events occur. After the first 6 to 12 months of therapy, if viral suppression is achieved, the patient has a CD4 count well above 350 cells/mL, and there are no active issues, patients may be monitored less frequently. While selection of antiretroviral regimens should be informed by an experienced HIV provider, once patients have achieved HIV-1 RNA suppression, their care might be managed by a primary care provider or geriatrician with consultation as needed.
Weight gain after ART initiation is common, clinically significant, and occurs even among those already overweight or obese, likely due to the decreased metabolic demand that results from effective viral suppression. While some weight gain may be beneficial among those who are underweight or normal weight, because weight gain is associated with incident hypertension, hyperlipidemia, diabetes, and hepatic steatosis, those who are overweight or obese should be counselled to reduce caloric intake or increase exercising to avoid gaining weight after ART initiation.
Chronic Disease Management
Even for the patient achieving and maintaining HIV-1 RNA suppression, aging with HIV is not the same as aging without HIV infection. Chronic HIV infection is a complex disease in which it is often impossible to tell whether a new condition is the result of HIV, HIV treatment, or comorbidity (and/or treatment for the comorbidity). In many cases, the likely answer is that there is no single etiology but rather the conditions results from a combination of some or all of these factors.
No one is immune from HIV infection. Nevertheless, HIV infection occurs more commonly among the homeless, members of inner-city minority or sexual minority populations, or those suffering from psychiatric illness compared with the general population of people 50 years of age or older. General medical comorbidities such as hypertension, diabetes, hepatitis C, and obstructive lung disease are common in these populations. Depression and severe mental illnesses such as psychosis and posttraumatic stress disorder are also more common among older people with HIV infection than among the general population of people 50 years of age or older. Older people with HIV infection may have multiple reasons to have cognitive dysfunction, whether from cognitive diseases of aging (multi-infarct dementia or Alzheimer disease) or from HIV (minor cognitive motor disorder or HIV-associated dementia).
As noted above, people aging with HIV infection are at higher risk for a number of age associated chronic diseases also associated with HIV (HANA conditions). While they do not appear to experience any one of these conditions dramatically earlier than demographically similar uninfected individuals, they do appear to experience a greater overall burden of disease from multiple conditions as reflected in greater polypharmacy, higher levels of physiologic frailty as measured by the VACS Index, decreased functional performance, and more substantial neurocognitive issues.
As a group, patients infected with HIV who are aged 50 years or older are also more likely than uninfected demographic counterparts to have consumed hazardous amounts of alcohol, use illicit drugs (especially marijuana, cocaine, and opioids), and smoke cigarettes. These behaviors increase risk of liver, lung, and heart disease. They also increase risk for a number of common cancers and contribute to neurocognitive dysfunction.
Among patients who continue to drink hazardously and or to use illicit drugs, adherence to antiretroviral therapy and ongoing organ injury are likely to be important issues. Patients should be asked directly about alcohol, cigarette, and illicit drug use, and encouraged to stop or curtail ongoing use. Any patient reporting current drug or alcohol use should be questioned closely regarding treatment adherence and monitored for signs of organ system injury.
More than half of HIV-infected patients smoke. Smoking increases the risk of pulmonary disease, cancer, cardiovascular disease, and fragility fractures, and impairs immune response to ART. It clearly increases risk of mortality. Recent analyses suggest that smoking is associated with a greater number of lost life-years than that associated with treated HIV infection.
Thus, it is important to encourage patients to stop smoking. The average successful patient will attempt quitting several times before succeeding. There are many excellent programs available to assist patients in quitting including online help programs. The use of nicotine replacement therapies may facilitate quitting. Early data suggest greater quit rates with varenicline, but greater adverse events.
Surprisingly little is known about the chronic effects of marijuana among middle-age and older individuals but what is known among younger individuals suggests that chronic use is likely to impair antiretroviral adherence and cognitive functioning and may contribute to obesity. There are no established pharmacologic treatments for marijuana use, but cognitive behavioral therapy or brief motivational interviewing would likely be helpful.
Even moderate levels of alcohol consumption may be harmful among those aging with HIV infection. This is, in part, because HIV infection alters the absorption of alcohol resulting in higher blood levels of alcohol among those with untreated HIV infection compared with uninfected individuals for the same amount of alcohol consumed. It remains to be seen if this difference persists after successful ART. Of note, on-going alcohol use may also impair efforts to stop smoking, to maintain a healthy body weight, or to successfully treat depression. Cognitive behavioral therapy or brief motivational interviewing can be effective alone or in combination with pharmacotherapy for those who drink at higher levels.
HIV-Associated Non-AIDS Conditions
After ART initiation, the incidence of AIDS conditions as defined by the Centers for Disease Control and Prevention drops dramatically and conditions such as Kaposi sarcoma, if present at diagnosis, may resolve without additional treatment. However, the Strategies for Management of Antiretroviral Therapy (SMART) trial demonstrated that viral suppression through ART also decreases incident non AIDS conditions including liver disease, kidney disease, lung disease, and cardiovascular disease, there are conditions for which those with HIV infection appear at greater risk even after adjusting for all established risk factors. The list of these conditions continues to grow and includes cancers associated with viral infections (eg, Hodgkin lymphoma, anal cancer, liver cancer), lung cancer, cardiovascular disease, liver cirrhosis, chronic obstructive lung disease, and renal failure. A hallmark of these conditions is that they are more common among those with unsuppressed HIV-1 RNA and/or lower CD4 cell counts compared with HIV infected individuals with suppressed HIV-1 RNA or higher CD4 cell counts and most are less common after ART initiation.
While the evidence for the association of these conditions with HIV infection compared with demographically and behaviorally similar uninfected individuals continues to grow, the mechanistic explanation for this association is likely complex. Potential mechanisms include immune dysfunction, dysregulation, and suppression; chronic inflammatory stimulation due to reservoirs of HIV-1 RNA replication and to chronic microbial translocation; hypercoagulability; and direct effects of viral proteins. Thus the biomarkers most relevant to studying this phenomenon have yet to be established and likely depend, to some degree, upon the condition in question.
Once people with HIV initiate ART, typically in their third or fourth decade of life, polypharmacy (being on five or more chronic medications) becomes the norm a full decade before those without HIV experience this syndrome. Further, due to the sensitivity of many antiretrovirals to drug-drug interactions and substantial preexisting organ system injury among those with HIV, those with HIV infection may be particularly susceptible to the harms associated with polypharmacy. These harms include decreased medication adherence and increased serious adverse drug events including organ system injury, hospitalization, geriatric syndromes (falls, fractures, and cognitive decline), and all-cause mortality.
In addition to antiretroviral medication, common medication classes among HIV-infected individuals with polypharmacy include antihypertensives, diuretics, statins, antidepressants, antacids, and nonopioid analgesics. Many of these medications have well established drug-drug interactions with commonly prescribed antiretrovirals. Of note, HIV-infected individuals are also experiencing an increasing rate of chronic prescription opioid and benzodiazepine use as has been documented in the general population. Of equal concern are medications taken over the counter and dietary supplements, which are almost never accurately documented in the medical record and may be particularly problematic. Recent IDSA guidelines recommend review of the complete medication lists with thoughtful consideration and discussion with the patient to try to prioritize medications and simplify regimens whenever possible.
It will also be important to attempt to keep the number of total medications (for HIV and non-HIV conditions) down in order to avoid drug-drug interactions and cumulative toxicity and to screen regularly for evidence of liver, kidney, and bone marrow toxicity. Antiretroviral treatment timing and choice should be made balancing the individual’s cumulative organ system frailty and their likely risk of adverse events against the substantial benefit of early and aggressive HIV treatment.
A large proportion of those with HIV infection in the United States are also infected with hepatitis C. The recent availability of highly effective and less toxic treatment for hepatitis C raises additional issues. HIV-infected individuals with hepatitis C coinfection experience more rapid progression of liver cirrhosis and a heighted risk of hepatocellular cancer. Recent data have demonstrated that suppression of HIV-1 RNA with antiretroviral treatment slows progression of liver disease among those coinfected with hepatitis C. Unlike HIV infection, hepatitis C can be cured. Given the substantial risk for cirrhosis, liver failure, and hepatoma among these individuals, it would seem appropriate to consider treating coinfected individuals earlier rather than later in the course of their disease.
The challenge for the aging patient with HIV infection and their provider is to balance screening and treatment for high risk, modifiable conditions including cancer, hypertension, hyperlipidemia, hepatitis C, and substance use against harm from polypharmacy. Whether or not a particular primary care practice is appropriate for an individual with HIV depends upon the individual’s life expectancy, the frequency and impact of the condition, the degree to which outcomes associated with that condition can be modified by timely medical intervention, and the risk associated with the intervention. For example, colon cancer screening via colonoscopy has a slight risk of perforation at the time of screen and a substantial risk of discomfort for the patient. Patients need to live at least 5 to 7 years after their screening for the benefit of the screening in decreased risk of death from colon cancer to outweigh the risk of perforation and the pain and discomfort of the procedure. Conversely, more aggressive screening for anal cancer may be indicated because of the increased incidence of this condition among those with HIV infection. Thus, it would be unwise to apply all “age appropriate” primary care guidelines for those without HIV to those with HIV infection without careful consideration for the individual’s prognosis, preferences for care, and personal risk of these conditions.
Finally, multimorbidity is the norm among those aging with HIV infection (Figure 128-2). Because of the overlapping complications and comorbid medical and psychiatric disease experienced by most patients with HIV infection, comprehensive care requires a team approach. No one specialist or generalist can hope to stay on top of optimal care in all these domains. HIV specialists need to turn to generalists and geriatricians when determining the best way to manage overlapping comorbid medical disease and to psychologists, psychiatrists, and social workers when managing psychiatric diseases. The management of alcohol and drug abuse also requires the insights of generalists familiar with the medical complications of these behaviors and of psychiatrics, psychologists, and social workers familiar with methods of managing these behaviors. In turn, generalists and geriatricians will need careful guidance from HIV specialists in determining when to start antiretroviral treatment, choosing optimal drug combinations, and determining when to stop or change therapy. For those who must manage patients far from specialty services, frequent telephone conferencing with specialists in HIV and with those experienced in the management of comorbid conditions is recommended.
Multimorbidity is the norm among those aging with HIV infection. Comparison of comorbid disease counts by HIV status. Conditions counted were diabetes, obstructive lung disase, liver disease, anemia, obesity, kidney disfunction, and hypertension. (Adapted from Salter ML et al. Clin Infect Dis. 2011;53(12):1256–1254.)