Chronic pain is a frequent comorbidity in people living with HIV (PLWH), with a 2014 systematic review finding a 54% (95% CI, 51.14%-56.09%) point prevalence.1 Causes of pain vary from the direct effect of HIV-induced peripheral neuropathy, neuropathic pain secondary to chronic inflammation, opportunistic infection, and adverse effects from exposure to antiretroviral therapy (ART). Chronic pain is known to be associated with impaired physical functioning, including mobility, self-care, and work and leisure activities,2 which may adversely affect ART adherence and retention in care. This potential effect of chronic pain on clinical outcomes is therefore an important consideration for HIV care providers.

A recent prospective cohort study published in JAIDS provided useful insights into what is increasingly recognized as a complex interaction.3 Data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a national clinic-based cohort of PLWH, were analyzed: 2334 PLWH were enrolled from 5 CNICS sites, and it was found that 25% experienced chronic pain (≥moderate pain for ≥3 months), 27% had suboptimal retention (no-show to a scheduled visit without another visit within 31 days), 12% had virologic failure (HIV RNA >1000 copies/mL at any point without a repeat test, ≤1000 copies/mL within 31 days), and 19% were prescribed long-term opioid therapy (opioid prescriptions covering ≥90 days consecutively).

For those not receiving long-term opioid therapy for chronic pain, there was an association between both suboptimal retention (adjusted odds ratio [aOR] 1.46; 95% CI, 1.10-1.93; P =.009) and virologic failure (aOR, 1.97; 95% CI, 1.39-2.80; P <.001). Compared with individuals with chronic pain who were prescribed long-term opioid therapy, virologic failure rates were significantly better (aOR, 0.56; 95% CI, 0.33-0.96; P =.03).

Of note, there was not improvement in retention in care for those with chronic pain who were receiving long-term opioid therapy compared with those with chronic pain not receiving long-term opioid therapy (aOR, 0.94; 95% CI, 0.64-1.38; P =.73). The study authors suggested that the protective effect of long-term opioid therapy for virologic outcome not only may relate to improved adherence but also could be an independent biological effect.

Infectious Disease Advisor talked to Jessica Merlin, MD, PhD, MBA, associate professor at the Divisions of General Internal Medicine and Infectious Diseases at the Center for Research on Healthcare, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Infectious Disease Advisor: Was the study designed primarily to elaborate on the effect of pain on healthy behaviors that affect HIV outcomes?

 

Dr Merlin: The a priori aim of the study was to investigate the relationship between chronic pain and key HIV outcomes, including retention and virologic suppression. We powered the study on the basis of the frequency of nonvirologic suppression, which is a rare outcome, so we wanted to make sure we had a big enough sample to be able to detect differences between groups. Our large, national cohort was particularly well-suited to address this question, as we had sufficient numbers to find relatively rare outcomes such as viremia and poor retention in care. As far as we are aware, there are no other studies that look at the relationship between chronic pain and virologic suppression in this large-scale way.

Infectious Disease Advisor: Your study showed that PLWH with chronic pain who do not receive long-term opioid therapy have a greater risk for virologic failure. What is the likely mechanism of this association?

Dr Merlin: I think you could hypothesize a variety of mechanisms for this association. From a clinical perspective, poor ART adherence is the likely mechanism, although we did not have the data to confirm this. We saw that chronic pain is associated with worse retention in care, and this may worsen adherence to ART. More research is needed to understand this mechanism, but we already know that health behaviors such as adherence and retention in care are really critical. We have antiviral medications that work well, so it’s uncommon that a patient cannot achieve virologic suppression based solely on their viral infection and the drugs available to treat it. For this reason, health behaviors become really important. Just coming to clinic and taking HIV medication is not always so easy, and understanding what influences those health behaviors is crucial. If we confirm that chronic pain affects ART adherence that would be a key finding.

 

Infectious Disease Advisor: What are the implications for this association between chronic pain and virologic outcomes?

Dr Merlin: Our study has shown an association between chronic pain and viremia, but I think it’s an open question as to whether treating pain improves viremia. Although I would hypothesize that it might, so this is something that we are very interested in investigating. We are planning a trial for a behavioral intervention for chronic pain in PLWH, looking at virologic outcomes, that has demonstrated early success in a pilot study. In addition, I think that we should look at the effect of treating pain with standard pain management plans, which improves virologic outcomes.

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Infectious Disease Advisor: Your study suggested that chronic pain may also be a biological factor in causing virologic failure, akin to depression. Are you aware of any markers of immunosuppression linked to chronic pain?

 

Dr Merlin: We’ve done some work published in JAIDS,4 looking at the relationship between particular inflammatory markers in PLWH who have chronic pain, and found that IL1ß is associated with chronic widespread pain in these patients (although this was not linked to viremia, as all the patients had previously achieved virologic suppression). We also conducted a study using standard tests of pain sensitivity in the laboratory (ie, hand in cold water, pressure pain, heat pain). We found that people with detectable viral loads are more pain sensitive than people without a detectable viral load. We also have some preliminary evidence that there are some biological factors that may be involved. Our future studies plan to look at this more carefully.

Infectious Disease Advisor: What do you think are the main takeaway points from this research?

 

Dr Merlin: In the last decade, we have learned much about other HIV comorbidities that have rightly received a lot of attention. But now, there is some momentum in the literature suggesting that chronic pain belongs among those comorbidities. Not only is chronic pain common and (from our earlier work) shown to affect function, but now it also affects HIV outcomes. I hope that this means that HIV providers and researchers will pay more attention to this important problem.

References

  1. Parker R, Stein DJ, Jelsma J. Pain in people living with HIV/AIDS: a systematic review. J Int AIDS Soc. 2014;17(1):18719.
  2. Merlin JS, Westfall AO, Chamot E, et al. Pain is independently associated with impaired physical function in HIV-infected patients. Pain Med. 2013;14(12):1985-1993.
  3. Merlin, J. S., Long, D., Becker, W. C., et al. The association of chronic pain and long-term opioid therapy with HIV treatment outcomes. JAIDS. 2018;79(1):77-82.
  4. Merlin, J. S., Westfall, A. O., Heath, S. L., Goodin, B. R., Stewart, J. C., Sorge, R. E., & Younger, J. IL-1β levels are associated with chronic multisite pain in people living with HIV. JAIDS. 2017;75(4):e99-e103.