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In this asynchronous online activity, we will be exploring timely clinical topics related to caring for people living with HIV.



Weight Gain and Integrase Inhibitors
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Consider the Following Case:

Amanda, a 46-year-old African American female, presents to your office for a follow-up visit.  She was diagnosed with HIV 10 years ago and has been doing well on a regimen of TDF/FTC/EFV with consistent viral suppression. In the past, she has declined a switch off efavirenz (EFV). She presents today and is ready to discuss a change. After a discussion, you both decide to change her regimen to TAF/FTC and DTG. She switches and has no tolerability issues.

Amanda returns in 1 month for a follow-up visit and complains that her clothes are tight and she has noticed a 10-pound weight gain since she started taking the regimen.

Data:

  • BP 128/80 mmHg
  • CD4 count-800 cells/mm3
  • HIV viral load-< 20 copies/mL

Questions for Discussion:

  1. Amanda asks if you think the new regimen is causing her weight gain. How do you counsel her?
  2. Would you switch her regimen? If so, to what?

19 thoughts on “Weight Gain and Integrase Inhibitors

  1. William Short says:

    Welcome to this new discussion topic. This question is one that I hear almost daily from patients after starting on ART and the most common question they have is ” Is this due to my medication”?

    Is this something you hear in your clinic? What do you tell patients? Do you switch their regimen? I can tell you that there is no right or wrong answer.

  2. Jason Schafer says:

    This case sounds like a very familiar situation that we have encountered a number of times in clinic over the last several years. We were concerned that that the weight gain patients were experiencing may be related to their ART and those concerns seem to have been validated with recent investigations involving INSTIs and TAF containing regimens. While those studies have been helpful, the degree of weight gain and in whom it occurs is quite variable and the reasons why remain unclear. Things also get a little less certain when talking to the patient, as they often mention 1-2 other factors that could be related to their recent weight gain (i.e. a change in diet, lack of activity, or just quit smoking). As a result, it is often difficult to assign all of the blame to the new ART regimen. It is also uncertain that weight gain would resolve after another change to the ART regimen.

    Given a lot of uncertainty in these cases, I think that an informed shared decision making approach with the patient is best. Letting them know that there is some evidence that their new ART can cause weight gain and giving them the option to change back to their previous regimen or an altogether new regimen. Really interested to hear how everyone else would approach this case.

    • William Short says:

      Jason I agree with you on all points. This area is difficult because this is new data emerging and we do not know which drug is contributing to the weight gain or is it a combination of drugs and we have no idea if the weight gain will decrease with switching a drug regimen.

      I am interested to see what others are doing or seeing in their clinics.

  3. Eileen Donaghy says:

    WEIGHT GAIN!! Usually a delicate topic to discuss with patients but much easier when the patient initiates the conversation and reports concern. Adding to the sensitive nature of the discussion- the patient is female and possibly peri-menopausal, age >40 which can all impact weight gain.
    Historically, as HIV providers, we have been trying to get our patients to gain weight. And our patients wanted to carry extra weight “it makes me look healthy” “no one will think I’m sick if I’m overweight”
    Now, in the age of INSTIs, we are faced with overweight patients who don’t appreciate the weight gain.
    Are we prepared to offer weight loss counseling or should we just change the regimen?
    Although we’ve seen much data supporting the issue of weight gain after initiating dolutegravir, I agree with Jason that ruling out other more “fixable” issues is very important.
    Has anyone referred patients to a nutritionist? or Weight Watchers? (cost supplemented by many insurances) or encouraged use of an APP to track intake and physical activity such as MyFitnessPal?

    • Jason Schafer says:

      I agree with Eileen that having the ability to refer patients for nutrition or weight loss management is important. It has definitely become much more common in my practice recently. We have a number of patients like the one in this case who may have the beginnings of metabolic syndrome, are at risk for developing diabetes, or may already have elevated cholesterol values and an increased risk for cardiovascular disease. The more we can do to help patients manage or prevent these complications, the better off they will be long term. These are the types of factors that I am contemplating when we suspect that a patient’s weight gain is ART related.

  4. Eileen Donaghy says:

    We have a nutritionist in our clinic but only 1 session monthly and many times patients don’t want to return at another day/time for counseling so I do much of it myself. I feel somewhat prepared to do this but time is a factor and there’s only so much you can accomplish in 30 mins.
    I check TSH and A1C levels and do a lot of pre-DM counseling.
    I also recently had 3 female patients, 50+years, complete bariatric surgery. We have definitely turned the corner from our patients wanting to be overweight as a sign that they are “healthy” to being much more conscious of risks of CV disease, HTN, DM2, and looking for weight loss options
    Does anyone follow a patient who has successfully lost significant weight following bariatric surgery?
    Is anyone else using A1C for screening?

    • Jason Schafer says:

      We also routinely screen for diabetes using A1C values in our patients. We have seen in the literature that weight gain among patients living with HIV (PLWH) on ART can lead to incident diabetes regardless of pre-ART weight (https://www.ncbi.nlm.nih.gov/pubmed/27171741). There is also some evidence that weight gain can influence cardiovascular disease risk (https://www.ncbi.nlm.nih.gov/pubmed/26216031) and so we are routinely evaluating patients for dyslipidemia and counseling patients on how to reduce their CVD risk starting with smoking cessation.

      Another potential confounder when it comes to weight gain and cardiovascular disease risk is tenofovir alafenamide (TAF). This recent meta-analysis identified a number of factors associated with weight gain in patients initiating ART, including INSTIs as well as TAF (https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciz999/5586728). We found a change in cardiovascular disease risk score when switching patients to TAF(https://academic.oup.com/ofid/article/6/10/ofz414/5571854?searchresult=1), but others have not found the same (https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofz472/5621345). Is anyone thinking about TAF in their patients who are experiencing weight gain or changes in cholesterol?

    • William Short says:

      There is data now that screening with A1C is not accurate for people living with HIV so we are changing the way we screen. We are using fasting blood sugars with their lab work.

      • Jason Schafer says:

        Bill brings up a really good point. A1C can underestimate glycemia in patients with HIV. This study (https://academic.oup.com/jac/article/69/12/3360/820631) suggests that using A1C as the sole diagnostic test in certain patients with HIV can lead to under-diagnosis and to under-treatment of diabetes. A higher than normal MCV in many patients with HIV seems to be at least part of the reason. I guess that the downside of relying on fasting blood glucose is ensuring that the patient was actually fasting for the test and having to get a positive result on two separate readings for a diagnosis.

        • Gwen Verlinghieri says:

          Hello Bill, Eileen & Jason, The topic of weight gain has come up in conversation in my patients, mostly in women of color. A few of these women have returned to care after being lost due to homelessness and drug use and another few who refused to come to an appointment, not willing to take their antiretrovirals who were living with shame and stigma. Dolutegravir with descovy was the regimen that these women were started on. The results were amazing – aside from the tolerability and rapid viral suppression, these once cachectic women were so happy to “finally not look sick.” Now that they are reengaged in care, they are referred to our full time nutritionist for healthy meal choices and we offer a nutritionist lunch daily to our clients. I have seen an increase in prediabetic labs in our patient population.

          • Eileen Donaghy says:

            Thanks Gwen. Providing a healthy lunch to your clients is very impressive. Are other offices able to provide meals to patients?
            It sounds like most try to work through the weight gain by using nutritional counseling as opposed to changing the antiretroviral regimen.
            Has anyone changed the regimen and seen weight loss?

  5. William Short says:

    Eileen I wonder the same thing about switching regimens. I have counseled patients that i am not sure if switching will help. I have now started discussing eight gain before I switch or start integrase inhibitors+/- TAF based regimens. I just had a pt on a BID raltegravir based regimen for years and we discussed changing to Biktarvy but she read about weight gain and declined. She said for now she will stay on a twice daily regimen until we have more information.

  6. Eileen Donaghy says:

    It will be interesting to see if we experience increased rates of DM2, HTN, CVD due to the increased weight gain attributed to these otherwise highly respected drugs. Is anyone experienced in prescribing weight loss medications or even tried Metformin?
    Jason- have you seen any of these drugs used and are there any drug/drug interactions we need to worry about?

  7. Idalina Afopa says:

    The increased risk of developing fat deposition has also been associated with older age, female gender. In addition, the increased weight gain in HIV patients may reflect the epidemic of obesity that is occurring in the general population, rather than being just an adverse effect of integrase inhibitors such as dolutegravir or bictegravir. In our VA HIV clinic, weight gain has not been a significant problem so far. However, HIV-infected patients are routinely assessed for abnormalities in lipid and glucose metabolism.
    In Amanda’s case, I would explain that there are other factors that could contribute to her weight gain but would be open to discuss the possibility of switching to another med regimen as this could end up in an adherence to ART issue.

    • William Short says:

      I agree that there is so much confusion as to what is going on with weight gain given the other factors that you mentioned. I think you really said it best-we (HIV providers) need to continue to assess for lipid and glucose problems.

      • Jason Schafer says:

        Yes, there could be a number of factors involved and I agree that taking a shared decision making approach with the patient in terms of switching their ART (or not) is best. As you said, additional problems could arise once a patient is switched to a new regimen, so any switch needs to be very carefully considered.

  8. ACTHIV Admin says:

    We hope you have found this interactive blog a valuable learning experience as a member of the HIV care team. Please note that this activity is now concluded and is no longer available for CME/CE credit. Please check the Short Scoops section of the website for additional blog activities which may be ongoing.

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