We found that HIV-infected and uninfected patients commonly received opioids. Consistent with previous literature, patients receiving opioids had a greater prevalence of HCV, major depression, alcohol and drug use disorders and pain-related diagnoses.4,7,12,38–41
Unique to our cohort, we demonstrated that these conditions were more common among HIV-infected patients who were prescribed opioids in comparison to their age/sex/race/ethnicity/site-matched controls. Generally, non-schedule II short-acting medications were the most common types of opioids received. After adjustment for established factors known to be associated with opioid analgesic receipt,4,5,23,40
HIV-infected patients were 40 % more likely to receive any opioids than uninfected patients. These associations were less pronounced for high-dose and absent for long-term opioid receipt. Pain-related diagnoses, HCV status and race/ethnicity were also important determinants of opioid receipt among both HIV-infected and uninfected patients. To our knowledge, this is the first study to examine patterns of opioid receipt among HIV-infected patients and matched controls in a Veteran sample.
We believe that the overwhelming majority of opioids were received for pain management, although a small number of prescriptions (e.g. codeine) may have been for cough. That a substantial proportion of both HIV-infected patients and uninfected patients lacked a documented pain-related diagnosis, may in part be explained by the limitations of administrative data,42
but the difference by HIV status was unexpected. The ICD-9 codes we included may have missed some pain syndromes which more commonly affect HIV-infected patients, such as herpes zoster or avascular necrosis. Coding practices among Infectious Disease vs. General Medicine providers may differ. These data are consistent with a prior study, which found that only 57 % of HIV-infected patients initiating opioid treatment had a documented indication for opioids.7
Our finding that HIV-infected patients were more likely to receive any and high-dose opioids, and less likely to receive long-term opioids are unlikely to be explained by differences in pain-related diagnoses alone. In fact, recent data from our group found that HIV-infected patients were less likely to report moderate or severe pain than uninfected patients (34 % vs. 49 %, p
0.05). These data suggest that variation among primary care providers and specialists in their approach to pain management may exist.
The increased prevalence of substance use disorders (and to a lesser extent major depression) among HIV-infected patients receiving opioids in our sample is of potential concern, as these characteristics are associated with opioid analgesic misuse.9,10,43–45
These findings contrast with data demonstrating that in patients with HCV, opioid analgesic misuse was not more common among patients with substance use disorders.38
Similar to prior studies, we found that being HCV-infected was associated with opioid analgesic receipt.38
Whether opioid receipt and outcomes differ among HIV-monoinfected and HIV/HCV-coinfected patients remains to be determined.
The prevalence of any opioid receipt and long-term receipt among HIV-infected patients deserves consideration. While HIV-infected patients frequently experience pain and are in need of effective treatment,13,17,46
data suggest there may be potential harm from opioids. For example, data indicate that compared to other analgesics, opioids are associated with increased cardiovascular events and fractures19,21
both of which occur more commonly among HIV-infected patients.26,47
Similarly, some evidence suggests that opioids may adversely impact the immune system.18
Our univariate analysis demonstrated a trend towards lower CD4 cell counts among patients on opioids, a finding that may be confounded by indication and did not persist in multivariable analyses. Prior studies are inconsistent in their findings about the association between receipt of opioids and HIV biomarkers.7,12,14
Whether in vitro effects of opioids on the immune system translate into clinical phenomena warrants further investigation.18
The potential for medication interactions with antiretroviral agents also requires consideration when considering some opioid analgesics, particularly methadone.22
In our sample, almost 5 % of the HIV-infected patients received methadone (data not otherwise shown).
The differences by race/ethnicity and receipt of any opioids, high-dose opioids and long-term opioid therapy are notable. The odds of receiving an opioid prescription was 20 % less in black patients compared with white patients. This difference by race/ethnicity is consistent with trends in existing literature in both general populations5,48
and HIV-infected patients in particular.12,14
Whether this reflects a difference in disease manifestations, patient experience of pain and preferences, indications for opioids for pain management, patient-provider trust,49
or a health disparity48
cannot be ascertained from these data, but deserves further investigation. HIV status, however, seems to mitigate differences observed by race/ethnicity, as the odds ratios were generally less pronounced among HIV-infected patients compared to uninfected patients.
Our study has some limitations. First, we were unable to capture pain severity and indication for opioids directly; instead, we relied upon ICD-9 codes. Second, ICD-9 codes may lead to under-reporting of conditions, which we used to identify pain-related diagnoses and comorbidities.42
Third, as our data were restricted to opioids obtained from a VHA pharmacy, we were unable to assess opioid analgesics received from outside sources. The VHA, however, offers generous pharmacy benefits28
and almost all HIV-infected patients receive their antiretroviral agents through the VHA.50
We did not assess provider types that prescribed the opioid medications. Finally, these findings may not be generalizable to female patients or to patients receiving healthcare in rural settings or outside the VHA.
In conclusion, opioid analgesics are commonly received by both HIV-infected and uninfected patients who have a high prevalence of comorbid diseases. Differences in documented pain-related diagnoses and opioid-receipt by HIV-infected and uninfected patients exist. HIV status remained an important determinant of opioid receipt even after adjusting for pain-related diagnoses, HCV status and race/ethnicity. Future work should be aimed at understanding these differences in opioid receipt by HIV status, by examining patient and provider-level factors that may contribute to this variation. In addition, work evaluating the associations between opioid analgesic receipt and important health outcomes among HIV-infected patients receiving opioids, such as the risk of developing opioid use disorders, infection, fracture and hypogonadism, is needed. Finally, given the prevalence and variations in opioid prescribing observed, future research should investigate the role of interventions to standardize documentation of pain diagnoses, dosing and duration of opioids across different clinical settings.