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Opioid Pain Medication in HIV+: affects brain, cognitive impairment; retention & viral suppression affects
 
 
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Below is link to report linking opioid use to increasing HIV replication & immune activation & inflammation in the brain & can cause cognitive impairment....Opioid medications are prescribed apparently to keep HIV+ adherent on ART to for complete & sustained viral suppression, but this paper found: "We found that in those with chronic pain, LTOT [long-term opioid therapy] was not associated with suboptimal retention but was associated with decreased odds of virologic failure..... The higher prevalence of prescription opioids in HIV-infected individuals is likely due in large part to the higher HIV-related illness burden resulting in increased chronic pain ......Chronic pain is a common comorbidity in people living with HIV (PLWH). The sources of chronic pain in PLWH are typically either neuropathic, musculoskeletal, or both, and occur in 30%-85% of individuals..... The few studies of chronic pain in PLWH suggest that chronic pain is strongly associated with functional impairment8 and may be associated with suboptimal adherence to antiretroviral therapy (ART)"....the 2nd study below found: The prevalence of prescribed opioids in HIV patients was highest for certain subgroups, including women, and those with a comorbidity and substance abuse history..... For many patients, lifelong infection and treatment is accompanied by high rates of pain and other clinical symptoms, with some studies indicating that up to two-thirds of patients on ART experience one or more clinical symptoms, most commonly gastrointestinal symptoms, body fat redistribution, myalgias, and paresthesias..... Thus, effective chronic pain management is an important consideration for HIV-infected patients, and one option for chronic pain management that is increasingly common in the general population is long-term use of opioid analgesics7. However, long-term treatment of pain with opioid analgesics in HIV-infected patients is complex given concerns of possible drug misuse since many HIV-infected individuals have a prior drug abuse history..... In this study, we determined that long-term prevalent opioid prescription use was more common among HIV-infected individuals compared with the general population. However, prevalence was increasing dramatically in the general population but was stable in the HIV-infected population. The strongest predictors of prevalent long-term opioid use in the HIV-infected population were female gender, HIV transmission by injection drug use, prior comorbidities and substance use disorders. Certain characteristics including older age and longer years known HIV-infected were only associated with prevalent long-term opioid use in 2005, while clinical characteristics, including higher HIV virus levels and a diagnosis of AIDS were only associated with prevalent opioid use in 1997. Depression diagnoses, which were common among HIV-infected individuals were also significantly associated with prevalent opioid use.
 
CROI/2018: The association of pain and long-term opioid therapy with HIV treatment outcomes - Chronic Pain Tied to Virologic Failure, While Long-Term Opioids Lower Odds of Failure
 
The association of drug abuse with prescription opioid use is consistent with earlier studies among HIV-infected individuals8, 29-31, as well as recent studies comparing prescription opioid use between those with and without substance use disorders in the general population18, 32. Those with diagnosed substance use disorders may have reduced pain tolerance23, 33, or perhaps increased prevalence of other comorbid illnesses34, resulting in more frequent use of prescription opioids at higher dosage levels. The higher prevalence of prescription opioid use in HIV patients with substance use disorders may also reflect increased risk of misuse of prescription opioids in this population. Clinical factors associated with prevalent long-term opioid use were high HIV virus levels, prior AIDS, prior depression and other comorbidity diagnoses.
 
In the absence of controlled trials evaluating the benefits and risks of long-term opioid use for chronic pain, it is difficult to know to what extent observed rates of long-term opioid use reflect excessive use of prescribed opioids in certain subgroups. Conversely, others have concluded that pain in HIV-infected patients may be undertreated29-30, 35. Although our study did not address the appropriateness of opioid prescription use directly, it is noteworthy that we found no differences by HIV infection status, after accounting for age and sex, in opioid dosing, or use of Schedule II drugs, suggesting that prescribing is similar in these populations. However, in a study of U.S. Veterans seen between 1998-2001, Hermos et al.36 reported that oxycodone/acetaminophen prescription use in HIV+ patients was more likely to be long-term rather than short- or intermediate-term, and more often associated with higher doses, suggesting a potential high risk prescribing pattern. Thus, further analysis of the appropriate management of chronic pain in HIV-infected individuals is warranted.
 
The Brain Affect of Opioids and Opioid Maintenance Therapies: Their Impact on Monocyte-Mediated HIV Neuropathogenesis: It has been shown that morphine enhances HIV infection of and replication in macrophages and other CNS resident cells (Fig. 1C)....Many factors have been proposed to contribute to this process. Morphine treatment of macrophages, derived from PBMC, increased surface expression of CXCR4 and CCR5, leading to increased susceptibility to infection by X4 and R5 viral strains [91]. In another study using human monocyte derived macrophages (hMDM), it was shown that morphine increased HIV infection of hMDM when an R5 strain was used [92]. These effects were mediated, in part, by increased surface CCR5, supporting the concept that morphine enhances HIV entry into macrophages by regulating the surface expression of its co-receptors [92].....Increased HIV infection of and replication in macrophages by opioids is important in the context of CNS viral reservoirs and neuroinflammation. Activation of HIV in macrophage reservoirs in the presence of opioids could lead to increased infection of other CNS resident cells, including microglia and astrocytes, which will also contribute to inflammation [95, 96]. Additionally, viral infection of macrophages increases the secretion of inflammatory cytokines and HIV proteins [97]. It has been shown that morphine enhances HIV mediated secretion of IL-6 and CCL8 from treated hMDM [98]. In addition, MOR activation on macrophages induces CCL2, CCL5, and CXCL10 (Fig. 1C) [77]. All of these factors contribute to CNS inflammation in the context of HIV infection [99]. Increased chemokine secretion will recruit additional monocytes into the CNS [49]. Inflammatory cytokines in conjunction with HIV proteins will mediate neuronal damage exacerbating cognitive dysfunction in the context of opioid abuse [100]. .....The effects of opioid maintenance therapies on immune cells, specifically on monocytes and macrophages, are important in the context of HIV infection and opioid abuse because they may impact chronic CNS inflammation that contributes to the development of cognitive impairment.....https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487025/
 
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Brief Report: The Association of Chronic Pain and Long-Term Opioid TherapyWith HIV Treatment Outcomes
 
We found that in those with chronic pain, LTOT was not associated with suboptimal retention but was associated with decreased odds of virologic failure.. We found several associations between chronic pain, LTOT, and key HIV care continuum measures.
 
Specifically, chronic pain in participants not on LTOT was associated with virologic failure and suboptimal retention. Although LTOT among participants with chronic pain was not associatedwith retention, we also found a previously undescribed protective association between LTOT and virologic failure. We believe chronic pain is akin to similar comorbidities that are also associated with virologic failure. For example, depression may lead to virologic failure due to both reduced ART adherence and also biological factors such as immune suppression.23 In addition, our finding is consistent with one previous study that found an association between physical symptoms and virologic failure.24 If future studies confirm that chronic pain directly contributes to virologic failure, this would reinforce the need to develop chronic pain treatments tailored to PLWH, and if effective, investigate whether they improve HIV-related outcomes. We also found that chronic pain was associated with suboptimal retention. Our analyses controlled for symptoms of depression/anxiety, current alcohol, and current illicit drug use, suggesting that chronic pain itself may have effects on daily life function that are independent of these related comorbidities. Therefore, additional work is needed to further understand these complex relationships.....Our study underscores the importance of chronic pain as a high-impact comorbidity among PLWH. Next steps include longitudinal studies with repeated measures of pain andopioid prescription that investigate directionality and causality. If studies confirm that chronic pain contributes to virologic failure, future work should include identifying effective chronic pain treatments for PLWH and investigating whether they improve HIV treatment outcomes. In addition, studies that assess potential unmeasured confounders of the association between LTOT and retention are needed.
 
Background: Chronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes.
 
Of the 577 participants with chronic pain, the most common pain locations were lower back (n = 411), numbness/tingling of hands and/or feet (n = 368), and knee (n = 278); 498 participants reported pain in more than one location. Symptoms of depression and anxiety were common.
 
.....a PLWH with chronic pain has 97% higher odds of having virologic failure without LTOT than a person without chronic pain without LTOT and has 77% (1 over 0.56) higher odds compared with someone with chronic pain on LTOT.In the sensitivity analysis excluding opium and codeine, and the analysis excluding participants who were viremic at baseline, there were no clinically or statistically significant changes in the relationships betweenPain/LTOT group and outcomes. In the sensitivity analysis excluding buprenorphine and methadone prescriptions in the adjusted model, the P-value changed from theoriginal 0.03 to 0.09. However, the point estimates were very similar (OR = 0.56 vs OR = 0.63). We believe that this difference is not sufficient to change our conclusions.

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Chronic pain is a common comorbidity in people living with HIV (PLWH). The sources of chronic pain in PLWH are typically either neuropathic, musculoskeletal, or both, and occur in 30%-85% of individuals.1-3 This wide prevalence range is likely due to variations in the populations studied and the methods of pain assessment.4 Potential reasons for disproportionately high rates of chronic pain in PLWH include: (1) HIV itself causes peripheral neuropathy,5 (2) exposure to certain older HIV drugs (eg, didanosine) can cause peripheral neuropathy,6 (3) shared risk factors for chronic pain and HIV, including mental illness and substance use,4 and (4) biological mechanisms such as chronic inflammation that may contribute to nonneuropathic chronic pain.7
 
The few studies of chronic pain in PLWH suggest that chronic pain is strongly associated with functional impairment8 and may be associated with suboptimal adherence to antiretroviral therapy (ART),9 but have not shown a relationship with virologic failure.
 
Recent evidence also suggests a complex relationship between chronic pain and another important HIV care continuum outcome, retention in HIVprimary care. We have shown that among PLWH with chronic pain, current illicit substance use is associated with missing fewer scheduled HIVprimary care visits ("no-shows"), a measure of retention in care.1 We hypothesized that this could be due to substance use driving clinic visit attendance to request or obtain prescriptions for opioids, but were unable to examine the role of opioids in that study. Notably, studies in theUnited States suggest that long-term opioid therapy (LTOT) is prescribed to as many as 17% of PLWH.10-12
 
Therefore, our objective was to investigate the impact of chronic pain on the key HIV care continuum outcomes of retention in HIV primary care and virologic failure. We also sought to understand the interplay between chronic pain and LTOT with respect to these outcomes.
 
Methods: This was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site.
 
Results: Among 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03).
 
Conclusions: Chronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration.
 
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PRESCRIPTION LONG-TERM OPIOID USE IN HIV-INFECTED PATIENTS
 
we confirmed here that a higher comorbidity burden was a strong predictor of long-term prevalent opioid use....Clinical factors associated with prevalent long-term opioid use were high HIV virus levels, prior AIDS, prior depression and other comorbidity diagnoses......In the absence of controlled trials evaluating the benefits and risks of long-term opioid use for chronic pain, it is difficult to know to what extent observed rates of long-term opioid use reflect excessive use of prescribed opioids in certain subgroups. Conversely, others have concluded that pain in HIV-infected patients may be undertreated.....In this study, we determined that long-term prevalent opioid prescription use was more common among HIV-infected individuals compared with the general population. However, prevalence was increasing dramatically in the general population but was stable in the HIV-infected population. The strongest predictors of prevalent long-term opioid use in the HIV-infected population were female gender, HIV transmission by injection drug use, prior comorbidities and substance use disorders....Depression diagnoses, which were common among HIV-infected individuals were also significantly associated with prevalent opioid use....The higher prevalence of prescription opioids in HIV-infected individuals is likely due in large part to the higher HIV-related illness burden resulting in increased chronic pain. However, it is notable that we observed a less rapid increase in opioid prescribing for HIV-infected patients compared with a doubling of the prevalence for the general population.....These results likely reflect the growing numbers of patients in these subgroups, accompanied by an increasing inclination for the treatment of pain in HIV patients with the longest exposure to HIV and/or prolonged exposure to antiretrovirals. Together, these opposing pressures on pain etiology and management may explain the stable trends in use of pain medication for HIV patients relative to the large increases observed for the population-at-large.....The association of drug abuse with prescription opioid use is consistent with earlier studies among HIV-infected individuals8, 29-31, as well as recent studies comparing prescription opioid use between those with and without substance use disorders in the general population18, 32. Those with diagnosed substance use disorders may have reduced pain tolerance23, 33, or perhaps increased prevalence of other comorbid illnesses34, resulting in more frequent use of prescription opioids at higher dosage levels. The higher prevalence of prescription opioid use in HIV patients with substance use disorders may also reflect increased risk of misuse of prescription opioids in this population.
 
Abstract
 
Objectives

 
To examine changes in use of prescription opioids for the management of chronic non-cancer pain in HIV-infected patients and to identify patient characteristics associated with long-term use.
 
Methods
 
Long-term prescription opioid use (i.e. 120+ days supply or 10+ prescriptions during a year) was assessed between 1997 and 2005 among 6,939 HIV-infected Kaiser Permanente members and HIV-uninfected persons in the general health plan memberships.
 
Results
 
In 2005, 8% of HIV+ individuals had prevalent long-term opioid use, more than double the prevalence among HIV-uninfected individuals. However, the large increases in use from 1997 to 2005 in the general population were not observed for HIV-infected individuals. The strongest associations with prevalent use among HIV-infected individuals were female gender with a prevalence ratio [PR] of 1.8 (95% CI=1.3, 2.5);Charlson comorbidity score of 2 or more (compared with a score of 0) with a PR of 1.9 (95% CI=1.4, 2.8); injection drug use history with a PR of 1.8 (95% CI=1.3, 2.6); substance use disorders with a PR of 1.8 (95% CI=1.3, 2.5). CD4, HIV RNA, and AIDS diagnoses were associated with prevalent opioid use early in the antiretroviral therapy era (1997), but not in 2005.

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Conclusions
 
Long-term opioid use for chronic pain has remained stable over time for HIV patients, while use increased in the general population. The prevalence of prescribed opioids in HIV patients was highest for certain subgroups, including women, and those with a comorbidity and substance abuse history.
 
The introduction of combination antiretroviral therapy (ART) in 1996 has resulted in substantially decreased mortality and AIDS-related morbidity for HIV-infected individuals. As a result, the HIV-infected population in developed countries is rapidly aging, with those greater than 50 years of age one of the fastest growing demographics1-2. HIV patient care, therefore, has shifted to a chronic disease model focusing on lifelong use of therapy, management of side effects, and increasing focus on age-related comorbidities. For many patients, lifelong infection and treatment is accompanied by high rates of pain and other clinical symptoms, with some studies indicating that up to two-thirds of patients on ART experience one or more clinical symptoms, most commonly gastrointestinal symptoms, body fat redistribution, myalgias, and paresthesias3-4. Pain in HIV-infected patients is generally chronic5, and results in significantly reduced quality of life6. Thus, effective chronic pain management is an important consideration for HIV-infected patients, and one option for chronic pain management that is increasingly common in the general population is long-term use of opioid analgesics7. However, long-term treatment of pain with opioid analgesics in HIV-infected patients is complex given concerns of possible drug misuse since many HIV-infected individuals have a prior drug abuse history8.
 
Furthermore, there are known drug-drug interactions for all antiretroviral drug classes with methadone and buprenorphine 9-12, and also for other opioid analgesics including meperidine10 and fentanyl13 coadministered with ritonavir-boosted antiretrovirals. The use of opioids for the treatment of chronic pain has increased markedly in the U.S.14, but there has been no evaluation of changes over time in opioid prescribing among HIV-infected individuals, nor a comparison of opioid prescribing in HIV-infected individuals compared with the general population. This paper compares trends in opioid prescribing between HIV-infected and HIV-uninfected individuals enrolled in integrated health plans between 1997-2005. We also evaluated whether demographic and HIV-associated clinical factors were associated with long-term prescription opioid use in HIV-infected individuals.
 
RESULTS
 
Descriptive characteristics for KPNC HIV-infected individuals with and without long-term prevalent use in 1997 and 2005 are presented inTable 1. In total, 6,939 HIV-infected KPNC members were eligible for one or more calendar years between 1997-2005, with a median of four eligible years contributed per person.
 
Univariate comparisons in 2005 indicated that prescription opioid users, compared with nonusers, were older, more often female, White, African-American, had more years known HIV-infected, more likely to report prior injection drug use, to have a prior depression diagnosis, have higher Charlson comorbidity scores, and less often Hispanic, other race/ethnicities, and men who have sex with men. Prevalent users, compared with nonusers, also had lower CD4+ T-cell counts, higher HIV RNA levels, and higher percentages with prior AIDS diagnoses and antiretroviral therapy experience. Similar results comparing users and nonusers were observed for 1997 (Table 1). All differences in these baseline measures between HIV-infected long-term opioid users and non-users were statistically significant at P<0.05.
 
DISCUSSION
 
In this study, we determined that long-term prevalent opioid prescription use was more common among HIV-infected individuals compared with the general population. However, prevalence was increasing dramatically in the general population but was stable in the HIV-infected population. The strongest predictors of prevalent long-term opioid use in the HIV-infected population were female gender, HIV transmission by injection drug use, prior comorbidities and substance use disorders. Certain characteristics including older age and longer years known HIV-infected were only associated with prevalent long-term opioid use in 2005, while clinical characteristics, including higher HIV virus levels and a diagnosis of AIDS were only associated with prevalent opioid use in 1997. Depression diagnoses, which were common among HIV-infected individuals were also significantly associated with prevalent opioid use. To our knowledge, this is the first analysis of trends in the use of long-term prescription opioid use for the management of chronic pain in HIV-infected patients. The trends observed among study subjects in Northern California were supported by similar trends among the study subjects in Washington State.
 
The higher prevalence of prescription opioids in HIV-infected individuals is likely due in large part to the higher HIV-related illness burden resulting in increased chronic pain23. However, it is notable that we observed a less rapid increase in opioid prescribing for HIV-infected patients compared with a doubling of the prevalence for the general population. It has been suggested that the increases in the general population may be due to either more pain-related diagnoses overall, or more likely, better patient and provider attention to pain and pain management7. The more stable prevalence over time in HIV patients may reflect opposing pressures on pain management and etiology over time. First, this analysis started near the beginning of the ART era when HIV/AIDS was transformed from a terminal illness to a chronic disease24. Therefore, earlier in the ART era, opioid management was more likely part of palliative, end-of-life care and consequently more liberal. Over time, the clinical management of HIV patients overall has improved, including substantial reductions in HIV-related complications, and improved tolerability of newer generation antiretrovirals12.
 
To offset this tendency for a decreased prevalence of prescription opioids over time, there are likely other factors resulting in a tendency for an increased prevalence. First, a consequence of the improved survival in the ART era for HIV patients is the higher burden of non-AIDS-related comorbidities25-26, resulting in the potential greater need for pain-related management. In support of this, we confirmed here that a higher comorbidity burden was a strong predictor of long-term prevalent opioid use. Second, HIV patients are also likely benefiting from improvements in pain management. Although we could not directly assess this possibility, it is noteworthy that older age and more years HIV experience were associated with higher prevalent opioid use in 2005, but not 1997. These results likely reflect the growing numbers of patients in these subgroups, accompanied by an increasing inclination for the treatment of pain in HIV patients with the longest exposure to HIV and/or prolonged exposure to antiretrovirals. Together, these opposing pressures on pain etiology and management may explain the stable trends in use of pain medication for HIV patients relative to the large increases observed for the population-at-large.
 
Long-term use of prescription opioids was strongly associated with HIV transmission by injection drug use, and substance use disorders diagnosed within the prior two years. These two factors were related in our data, but included little overlap. To illustrate, in 2005, of those with a substance use disorder in the prior two years, 16% had an HIV transmission risk factor of injection drug use, compared with only 5% among those without prior substance use disorders. Thus, most HIV-infected individuals identified here with a prior substance use disorder did not have a recorded HIV exposure transmission of injection drug use. This is relevant since such diagnoses if made in the Chemical Dependency or Psychiatry departments, may not have been known to prescribing physicians outside these departments, including HIV clinicians. Diagnoses are not disclosed to such prescribing physicians because of Federal 42CFR Part 2 privacy regulations, which prohibit any disclosure of chemical dependency visits or diagnoses (or in the Psychiatry department when Chemical Dependency is affiliated with Psychiatry), to other departments in the same health plan27-28. Thus, careful screening by the prescribing physician for the potential abuse of prescribed opioids or existence of a substance abuse problem is needed, particularly in HIV-infected individuals who are more likely to have a substance abuse history compared with the general population.
 
The association of drug abuse with prescription opioid use is consistent with earlier studies among HIV-infected individuals8, 29-31, as well as recent studies comparing prescription opioid use between those with and without substance use disorders in the general population18, 32. Those with diagnosed substance use disorders may have reduced pain tolerance23, 33, or perhaps increased prevalence of other comorbid illnesses34, resulting in more frequent use of prescription opioids at higher dosage levels. The higher prevalence of prescription opioid use in HIV patients with substance use disorders may also reflect increased risk of misuse of prescription opioids in this population. Tsao et al.31, for example, evaluated 2267 HIV-infected individuals in 1996-1997 in the HIV Cost and Services Utilization study (HCSUS) and found an increased risk of pain and aberrant opioid use among those with a drug abuse history (n=870) compared with those without a drug abuse history (n=1397). Those with a history of drug abuse also persistently reported aberrant opioid use during follow-up. Another study of 190 HIV-infected individuals seen in a single U.S. medical clinic indicated that HIV-infected individuals with a history of IDU were more likely to have been prescribed narcotics inappropriately compared with other men who have sex with men or heterosexuals8.
 
Clinical factors associated with prevalent long-term opioid use were high HIV virus levels, prior AIDS, prior depression and other comorbidity diagnoses. HIV virus levels and AIDS were associated with opioid use in 1997 but not in 2005, which again likely reflects the improving prognosis for HIV/AIDS patients over time and availability of better tolerated therapy. Prior studies have not evaluated such factors with respect to opioid prescribing, although some have reported that these same clinical factors were associated with reported clinical symptoms among HIV-infected persons4. Other demographic factors associated with prevalent opioid use in our study were female gender, older age, and more years known HIV-infected.
 
In the absence of controlled trials evaluating the benefits and risks of long-term opioid use for chronic pain, it is difficult to know to what extent observed rates of long-term opioid use reflect excessive use of prescribed opioids in certain subgroups. Conversely, others have concluded that pain in HIV-infected patients may be undertreated29-30, 35. Although our study did not address the appropriateness of opioid prescription use directly, it is noteworthy that we found no differences by HIV infection status, after accounting for age and sex, in opioid dosing, or use of Schedule II drugs, suggesting that prescribing is similar in these populations. However, in a study of U.S. Veterans seen between 1998-2001, Hermos et al.36 reported that oxycodone/acetaminophen prescription use in HIV+ patients was more likely to be long-term rather than short- or intermediate-term, and more often associated with higher doses, suggesting a potential high risk prescribing pattern. Thus, further analysis of the appropriate management of chronic pain in HIV-infected individuals is warranted.
 
There were study limitations. First, depression, substance use disorder diagnoses, and other medical comorbidity data were ascertained from automated diagnostic data, and may have been underreported, although not likely to be different between those with and without prescription opioid use. Furthermore, these variables were not available for analysis of factors associated with prescription opioid use in 1997. However, exclusion of these variables from the final multivariable model in 2005 had no effect on the magnitude of PRs for other variables (data not shown). An additional limitation was the lack of information regarding indications for opioid prescribing, including types of pain experienced. Such information would be valuable for a refined understanding of the etiology and treatment of chronic pain in HIV patients. An additional limitation is the lack of generalizability to those without health insurance, or to other healthcare systems that are not guided by an integrated health care delivery model. However, the comparable trends observed within two separate health plan systems suggest highly generalizable results for other similar healthcare systems with comprehensive medical coverage. In summary, we determined that HIV-infected individuals have a higher prevalence of long-term prescription opioid use compared with the general population, although prevalence in the HIV-infected population was stable whereas general population rates were increasing rapidly. HIV disease severity and HIV treatment experience were not predictive of opioid use in the most recent study year, suggesting improvements over time in the tolerability of antiretrovirals. We also determined that certain subgroups had increased long-term opioid use, particularly those with a history substance use disorders. These results are relevant to strategies for management of chronic pain in HIV-infected individuals. Specifically, careful screening for substance use problems is warranted when considering long-term medically prescribed opioids in this population.

 
 
 
 
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