Siriimu and fats

The Luganda word for HIV/AIDS is "siriimu". This might not mean anything to you at first, but then let me tell you that in this language R's are pronounced like L's; now you can read it as "silimu", or "slim". HIV/AIDS:  the disease that makes you skinny.

Advanced HIV infection, both alone and in combination with other illnesses that often occur with it (particularly TB), causes wasting. Wasting is more than undernutrition; by definition, it cannot be reversed by nutrition alone. It is the result of a chronic disease process involving a high metabolic state due to constant inflammation in the body, made worse by opportunistic infections in the gut that cause diarrhea and malabsorption. (Actually, a lot of what is known on this subject - ie, cell signaling molecules like tumor necrosis factor alpha, TNF-a, that are thought to be major causes and treatment targets for wasting - have been discovered through research on end-stage cancer. Cancer wasting is also called "cachexia".) Because lean body mass is disproportionately lost in this process, people who are wasted look different from people who are just really skinny. Loss of their facial muscles leaves noticeable depressions around the temples and jaws:

Moderate temporal wasting in an HIV-positive woman

In Uganda, where HIV is fairly prevalent, divots on both sides of someone's face should make you think of HIV/AIDS. (Where HIV is rare, you would think of end-stage cancer.) Many of our sickest clinic patients had profound temporal wasting before they started antiretroviral medications (ARVs). And outside of clinic, while boarding a taxi in Kampala or grabbing lunch in a restaurant in Kiboga, it's not uncommon for me to catch sight of a skeletal face and mentally diagnose advanced HIV.

That said, the appearance of siriimu is very different today than it used to be. When advanced HIV got the name of "slimming disease" there was no treatment for it, and skeletal faces must have been everywhere in the streets and hospitals. These days, ARVs are turning the disease process around:  they reduce HIV viral load, increase CD4 immune cell function, stop TNF-a overactivity and wasting, and plump up the faces and bodies of HIV-infected persons. You could say that they are literally "changing the face" of the disease! And this antiretroviral therapy (ART)-associated weight gain can be quite striking. Wasted and tired-looking patients whom we start on ARVs often come back for the two-week check-up with round cheeks and big smiles; at the six-week treatment follow-up, we have documented ~10 kg (22 lbs) of weight gain in several patients. Preliminary data from our study shows that this weight gain continues, albeit at a slower rate, over the first six months on therapy. Our average patient gains almost 3 kg (6.5 lbs) in that time period, and a handful have gained upwards of 15 kg (33 lbs).

Unfortunately, ART-associated weight gain may not be all good. There is strong evidence that certain ARVs cause unhealthy fats to accumulate in the body, both as deposits in blood vessels (a precursor for atherosclerosis, which causes blood clots or vessel narrowing/blockages) and as abnormal distributions of fatty tissue around the body (called lipodsytrophy, which is associated with metabolic disorders like diabetes). The second effect, lipodystrophy, can be easily picked up in a physical exam:  its hallmark signs are fatty accumulation around the abdomen and upper back, plus/minus fatty loss from the face and arms. So we assess body shape and waist-to-hip ratios at every visit, and we also check fasting blood sugar levels to see if our patients are developing diabetes. So far, we haven't seen these kinds of changes - happily, round cheeks predominate over rotund bellies! - but it's too early to conclude anything. Many patients have only completed the early stages of follow-up, so we have a lot more data to collect. Fatty deposits in the blood are harder to detect in a physical exam, but we perform monthly blood pressure checks to get some idea of what's going on inside. We haven't seen any trends toward fatty deposits and stiff blood vessels yet - but again, these changes may take longer to become obvious. In order to answer this question, we are planning a long-term study on heart disease risk, including annual blood tests for cholesterol and other fats and EKGs to assess for heart attacks, that would follow a subset of our patients before and during the first five years on ART.

As you can see, the interactions between HIV, ART, and fats are complex. There is uncertainty around how much weight gain is healthy on ART, how best to measure heart disease and metabolic risk factors in such patients, and how to balance to benefits and side effects of ARVs. Last week we all cheered for a man who proudly waltzed into clinic with 8 kg weight gain in the past month on treatment. But doubt quickly set in. Is that rate of weight gain healthy? Is his new fat in the right proportions and places? Do we really know enough to celebrate? My colleague congratulated the patient and then whispered in my ear, "I just hope that this is as good as we say it is!" Solemnly, I had to agree.

I am not sure about the true nature of rapid weight gain on ART, but hopefully soon an answer will emerge from our accumulated clinical experiences. All the while, it's fascinating to witness the dynamic nature of a disease. In just one decade, since ARVs came to Uganda, HIV/AIDS has gone from "the slimming disease" without any treatment to an impressive plumped-up state on ART. Emaciated patients appeared saved; a solution appeared found. But, now that people with HIV are living longer than ever, we are finding that their additional years are pock-marked with above-average rates of chronic diseases like high blood pressure and diabetes. Our "solution" actually creates new problems. Yes, these are secondary concerns - better to have heart disease at 60 than be dead at 26 - but still they are serious, and they are going to affect millions.

Through this unfolding tale, I am reminded that medicine is the eternal student of the human body, A Quite Mysterious Teacher! As we try to understand the body's complex responses to every intervention we create - a new chemical to swallow, a diet to control all inputs, an operation to modify or remove organs, a few blasts of radiotherapy - we must be humble, ask questions, take good notes, and be ever-ready for the next surprise lesson.