Is HIV-associated wasting still a concern today?

I can still remember the days when I was a third-year medical student just starting my clinical in-patient rotations in 1993. The first person I was assigned to take care of was John (not his real name), who was 34 years old and living with HIV/AIDS. His T cell count was extremely low at 5 cells/µL and his HIV viral load was over 750,000 copies/mL. He sat there in the hospital bed weighing about 100 pounds soaking wet, despite being about 6 feet tall. His face was gaunt and I could see the hollowing in his temples and cheeks. I introduced myself as a medical student who was going to take care of him. He managed to eke out a wry smile as he allowed me to ask him questions about his current condition and to perform a physical exam.

I remember placing my stethoscope on the front part of his chest to listen to his lungs and heart, but was struck by how prominent his ribs were. Usually, the drum of the stethoscope should be able to lay flat on the skin. However, because John had lost so much weight, there were indentations between his ribs and it was difficult to listen to his lungs and heart because the stethoscope laid on his bones, instead of being flush on the skin. His arms and legs were extremely thin and I could see the outlines of his muscles. Those were the early days of the HIV epidemic, prior to the development of highly active antiretroviral therapy (HAART).

John told me that he normally weighed about 180 pounds but had been losing a ton of weight over the past six months. He explained that he had become essentially bedbound because he had no energy and no endurance to do much. Despite having a good appetite and trying to eat as much as possible, he continued to have endless bouts of diarrhea with weight loss until he finally went to get tested for HIV and found out that he was positive about a month prior to his hospital admission. At that time, there were a few HIV medications available, such as AZT, but he had heard of many friends who had taken them and had experienced side effects such as severe nausea and headaches. Thus, he had chosen not to take any anti-HIV medications. It was soon after that day that my first patient with HIV, John, passed away.

John’s story was classic for someone with HIV-Associated Wasting (HIVAW), which is a serious condition seen in people with advanced HIV/AIDS. John exhibited the common symptoms of wasting including involuntary weight loss, extreme fatigue, low energy and diffuse muscle weakness. Later in 1987, the CDC defined HIVAW as an involuntary weight loss of at least 10% of baseline body weight plus either chronic diarrhea or chronic weakness and documented fever for at least 30 days that is not attributable to a concurrent illness or condition other than HIV infection itself that could explain the findings¹. HIVAW was a potentially life-threatening complication associated with significant illness and risk of death^2,3.

Enter the HAART era

Since the introduction of HAART in 1996, significant improvements in health have been achieved for people living with HIV (PLWH), especially in regards to their immune function and their overall quality of life and well-being. As a natural consequence, it is often assumed that HIVAW no longer remains a threat as long as one remains on HAART. Thus, wasting has been often forgotten and overlooked in the post-HAART era^4-6.

However, the impact of wasting cannot be understated. In the early-HAART era, a weight loss of greater than or equal to 10% from baseline was significantly associated with a four- to six-fold increased risk of death compared to people who maintained or gained weight⁶. A recent presentation at ID Week in October 2022 evaluated the association between newly diagnosed HIVAW/low weight and found that it was associated with twice the risk of death despite whatever HIV viral load or the number of comorbidities that the PLWH had⁷. In addition, people with HIVAW were more than twice as likely to be hospitalized, had five times the number of hospitalizations and had twice the number of emergency department visits per year, thus leading to a 1.3 times higher economic overall cost/burden compared to those without HIVAW8.

A new definition

Prior to the HAART era, the prevalence of HIVAW was estimated at 25–30%^9,10. This was thought to be an underestimate because the old CDC definition of HIVAW excluded PLWH who had only weight loss but no symptoms, which was quite common. In the current practice of HIV medicine, the old CDC definition of HIVAW is not useful clinically because PLWH are usually started on HAART soon after their diagnosis and we do not see the chronic diarrhea, weakness, or fevers lasting 30 or more days. As a result, the definition of HIVAW was refined to reflect a more appropriate and meaningful approach to diagnosing a PLWH with HIVAW. This newer definition redefines HIVAW as “unintentional loss of body weight or lean body mass, as well as reduction in physical endurance and overall function”¹¹. Thus, this improved definition relies less on the exact amount of unintended weight loss but instead emphasizes the downstream effect of that muscle/weight loss on physical function and endurance.

Current research

Few studies have looked at the incidence or prevalence of HIVAW in the post-HAART era until more recently. Javeed Siddiqui and colleagues conducted a database analysis of healthcare claims data for commercial health plan enrollees with HIV infection between January 2005 and July 2007 and found that 8.3% had evidence of HIVAW¹². Those with HIVAW were generally older and male.

The same investigators recently performed another medical and pharmacy claims database study using IBM MarketScan Commercial, Medicare Supplemental and Medicaid Databases between 2012 to 2018 and estimated the cumulative HIVAW prevalence to be 18.3% or about 3.1% annually¹¹.

Michael Wohlfeiler, MD, and colleagues recently evaluated the incidence of HIVAW in the OPERA observational cohort, which includes prospectively captured clinical data from electronic health records of approximately 13% of PLWH in the U.S.¹³. Incident HIVAW was identified in 7% of this population from 2016 to 2020, which is equivalent to an annualized incidence of 1.75% per year¹³. Advanced HIV disease and the presence of comorbidities significantly predicted the new onset of HIVAW/low weight¹³. The authors also concluded that assessment of frailer PLWH for wasting should be prioritized.

Still here

Given that PLWH are living longer and may be aging a bit faster than people without HIV, older individuals may be at higher risk for developing HIVAW as they age.

While it is true that we do not see the high incidence and prevalence of wasting that we used to see in the pre-HAART era, HIVAW still does exist. However, the clinical presentation of someone now with HIVAW is much different and more subtle than previously seen. In my own subspecialty Owen Metabolic Clinic, I see many PLWH specifically for evaluation of HIVAW and weight loss. These patients do not have a similar story as John. The majority of them are well-controlled from an HIV standpoint and have stable CD4 counts usually above 350 and undetectable viral loads on HAART. The weight loss is not necessarily rapid, but tends to be a slower weight loss that occurs over months despite what seems like an adequate appetite and food intake.

In my opinion, in the HAART era, the usual presentation of someone with HIVAW is less associated with dramatic weight loss, but more associated with the lack of physical energy and endurance to complete desired activities and even basic daily activities of living. Thus, it is vital for PLWH and medical providers alike to keep in mind the possibility of HIVAW in aging individuals who experience fatigue, low energy, and muscle weakness because treatment may improve these symptoms.

Treatment options

The treatment of HIV-associated wasting must be individualized as the cause or causes of wasting in each patient is uniquely different14. Anorexia, if present, may be corrected with appetite stimulants. All patients with wasting should also be evaluated by a registered dietician (if accessible) to review their nutritional intake. If virologic suppression is inadequate, either starting an antiretroviral regimen or changing an existing regimen to achieve an undetectable plasma HIV RNA—undetectable viral load—may help in preventing further loss of body cell mass. Opportunistic infections, malignancies and gastrointestinal infections should be treated when present. Progressive resistance exercise can be useful in maintaining and increasing lean body mass (LBM) in people who are able to exercise. Those with evidence of testosterone deficiency may also benefit from replacement therapy with testosterone. For those without hypogonadism, anabolic steroids may be helpful in improving lean body mass. Lastly, the FDA has approved a recombinant human growth hormone as a possible treatment for patients with HIVAW.

Conclusion

HIVAW still exists in the HAART era. Although the incidence and prevalence is lower than the early pre-HAART era, HIVAW remains associated with potentially high risk of illness and death if left untreated. Awareness of the current presentation of HIVAW and having a high level of suspicion to screen PLWH is ultimately the key in making the diagnosis of HIVAW. The etiology of wasting is often multifactorial and treatment needs to be individualized and targeted towards the underlying cause(s) in order to improve each patients’ HIVAW symptoms.

Footnote references

Positively Aware received an unrestricted grant from EMD Serono, the healthcare business of Merck KGaA, Darmstadt, Germany in the U.S. and Canada. Dr. Lee serves as a paid consultant to EMD Serono. His statements and viewpoints are his own and were not influenced by EMD Serono.