Do Integrase Inhibitors Affect Testosterone Levels in Men?

March/April 2017

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Bear in Mind

  1. This study's design is cross-sectional in nature; data were captured largely at one point in time. Cross-sectional studies are good at finding associations between a drug and, in this case, a problem (hypogonadism). However, cross-sectional studies by their nature can never prove cause and effect (that is, that integrase inhibitors cause hypogonadism). Cross-sectional studies are a good starting point to begin to explore a research question. If something interesting turns up, it can then be better understood in a study of a more robust statistical design.
  2. There were only 14 men who used integrase inhibitors in the French study. This is insufficient for drawing robust conclusions about the impact of this class of medicines on testosterone levels (or anything else). The researchers stated that they were surprised by the association between integrase inhibitors and low testosterone, which is understandable because integrase inhibitors have been in use for about a decade in high-income countries. Also, it is odd that no other team of researchers has found this connection. Furthermore, in other studies, low testosterone has been found in HIV-positive men who were not taking ART and, in men who were taking ART before the introduction of integrase inhibitors.
  3. The French researchers stated that they found an association between low testosterone and integrase inhibitors. However, this conclusion could have been skewed by other factors that were unmeasured by their study. For instance, why were some patients given integrase inhibitor-based therapy and others were not? What was the medical history of these patients? Researchers did not apparently screen participants for the presence of all major ED risk factors. Furthermore, the researchers did not address these points in their analysis. It may be that doctors had reasons for prescribing the anti-HIV drugs that they did, and that by chance people with low testosterone just happened to receive integrase inhibitor-based therapy. Such are some of the problems that can bedevil a cross-sectional study and the conclusions drawn from such studies.
  4. What can be reasonably extracted from the present study is the following:
    • free testosterone measurements are useful
    • some HIV-positive men have lower-than-normal levels of testosterone
    • ED is common among HIV-positive men


What Needs to Be Done

The role of HIV treatment on testosterone levels (and ED) needs to be explored in a study of a more robust statistical design. Such a study would have many more participants, but size alone is insufficient to prove cause and effect. Ideally, as part of some randomized clinical trials, men would be screened for risk factors both for ED and low testosterone prior to initiation of ART and monitored while taking anti-HIV treatment. However, large, well-designed studies are expensive. In an era of austerity, it may take time to raise the funds necessary for such a large and well-designed study. The French researchers stated that they are engaged with a larger study to confirm their findings but did not state details as to that larger study's design.

It is good that some researchers, such as the present French team, are interested in studying testosterone levels and why some HIV-positive men might have lower-than-normal levels. The findings from the French study are certainly interesting and should be seen as a beginning and not an end to understanding the issue of low testosterone and ED and their possible causes in HIV-positive men. Hopefully, the French study will stimulate other researchers to conduct further explorations on testosterone, ED and its relationship, if any, with HIV treatment. However, for now, any link between their findings on testosterone and the use of integrase inhibitors must be treated with caution until they are confirmed in a study that is statistically more robust.


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  1. Lachâtre M, Pasquet A, Ajana F, et al. HIV and hypogonadism: a new challenge for young-aged and middle-aged men on effective antiretroviral therapy. AIDS. 2017 Jan 28;31(3):451-453.
  2. Wunder DM, Bersinger NA, Fux CA, et al. Hypogonadism in HIV-1-infected men is common and does not resolve during antiretroviral therapy. Antiviral Therapy. 2007;12(2):261-5.
  3. Collazos J, Esteban M. Has prolactin a role in the hypogonadal status of HIV-infected patients? Journal of the International Association of Physicians in AIDS Care. 2009 Jan-Feb;8(1):43-6.
  4. Lamers SL, Rose R, Maidji E, et al. HIV DNA Is frequently present within pathologic tissues evaluated at autopsy from combined antiretroviral therapy-treated patients with undetectable viral loads. Journal of Virology. 2016 Sep 29;90(20):8968-83.
  5. Jenabian MA, Costiniuk CT, Mehraj V, et al. Immune tolerance properties of the testicular tissue as a viral sanctuary site in ART-treated HIV-infected adults. AIDS. 2016 Nov 28;30(18):2777-2786.
  6. Slama L, Jacobson LP, Li X, et al. Longitudinal changes over 10 years in free testosterone among HIV-infected and HIV-uninfected men. Journal of Acquired Immune Deficiency Syndromes. 2016 Jan 1;71(1):57-64.
  7. De Ryck I, Van Laeken D, et al. Erectile dysfunction, testosterone deficiency, and risk of coronary heart disease in a cohort of men living with HIV in Belgium. Journal of Sexual Medicine. 2013 Jul;10(7):1816-22.
  8. Biebel MG, Burnett AL, Sadeghi-Nejad H. Male sexual function and smoking. Sexual Medicine Reviews. 2016 Oct;4(4):366-375.
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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.

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