July 2020: HIV and STIs

Improving the delivery of chronic opioid therapy among PLWHIV: a cluster randomized controlled trial.  I’m generally anxious when writing about long-term opioid prescribing, something I was never sure that I was doing “right” and am glad to have left for others.  My primary care training took place mostly in the VA system at a time when the VA was taking a hard turn against chronic use of opioids – if you didn’t have cancer and wanted something stronger than tramadol (an opioid that somehow we’d all decided wasn’t?) on ongoing basis, you got a prescription for acetaminophen and a referral to a “pain service” that 1) also didn’t prescribe opioids and 2) was mostly useful for getting your patient’s ire directed at someone else.  This authors of this study suggest I’m not alone in that discomfort, pointing to literature that indicates low confidence in and satisfaction with pain management among HIV clinicians, as well as both underprescribing and overprescribing behaviors. 

The authors organized the TEACH collaborative care intervention trial, which recruited HIV physicians and APPs from two safety-net clinics in Boston and Atlanta and their patients receiving chronic opioid therapy (defined here as 3+ opioid prescriptions 3+ weeks apart within a six-month period).  Providers were randomized to receive an intervention consisting of a didactic on opioid prescribing, longitudinal feedback on their opioid prescribing, enhanced access to addiction specialists, and a dedicated nurse manager for assessing and monitoring patients receiving opioids, or no intervention.  The primary outcomes of the study were rate of 2+ urine drug tests completion (for clinicians) and rate of any early refills at 12 months (for patients).  Secondary outcomes for clinicians included rates of use of opioid treatment agreement, use of the PDMP, and rates of >3 primary care visits at 12 months; secondary outcomes for patients included pain severity and interference with ADLs, and scores from two validated tools assessing opioid and non-opioid substance misuse.

A total 41 HIV clinicians (32 physicians and 9 APPs) participated in the trial. The clinicians cared for a total 187 patients receiving COT, of whom 114 agreed to enroll in the observational cohort and completed a baseline assessment; the mean patient age was 53, a third were women, 23% were white, and 8% were Hispanic.  The primary outcome for clinicians (% of patients with 2+ urine drug tests from baseline to follow-up) was dramatically higher in the intervention arm (71% vs 20% with an aOR of 13.4; 95% CI 5.9-30.6), as was the rate of having an opioid use agreement (aOR 61.5 with 95% CI 15.3-247.2).  No difference between the intervention and control groups was found for either use of the PDMP or having 3+ primary care visits with a patient per year.  The primary outcome for patients (% with any early opioid refill) was no different between the intervention and control groups (22% vs 30%; aOR 0.6 with 95% CI 0.3-1.2), nor were any of the secondary outcomes, including assessments of opioid misuse- though of note, patients of clinicians in the intervention arm had nonsignificantly higher pain severity and ADL impairment scores, as well as nonsignificantly higher rates of opioid discontinuation (30% vs 26%) and hazardous alcohol use (18% vs 10%).  On the bright side, patients in the intervention arm had nonsignificantly higher rates of virologic suppression (<200 copies/ml; 87% vs 82% in the control arm, aOR 1.2 with 95% CI 0.5-3.1).

The authors conclude that their intervention led to statistically significant improvements in “two recommended features of appropriate care for patients on COT: completion of >2 UDTs and opioid treatment agreements”.  Unfortunately, the authors do not use the discussion section to grapple with the question of why obtaining more UDTs or treatment agreements is a good thing, nor do they comment on the (numerically but nonsignificantly) greater pain severity, pain-associated debility, and alcohol misuse in the intervention arm.  Why is how well clinicians police their patients a more appropriate clinical outcome than those patients’ degree of pain and quality of life?  “Guidelines adherence” should not be uncritically accepted as a good, especially when IDSA’s 2017 guidelines on chronic pain in PLWH states that “the efficacy of [opiate treatment agreements] in reducing prescription opioid-related harm is not well established” and notes both the absence of quality data associating UDT testing with improved clinical outcomes and that “[u]rine testing can create an environment of mistrust and further stigmatize the use of opioids for pain in a population of patients who, by virtue of their HIV and chronic pain diagnoses, are already stigmatized”.  I would like to see a version of this study designed and powered to identify an improvement in virologic suppression, patients’ reported pain or functional status, or a reduction in complications of opioid use – in my view, far more important outcomes. 32697847

HIV is associated with dementia in older veterans. HIV both infects the CNS and induces a chronic inflammatory state that is clearly associated with coronary vascular disease and also contributes to cerebrovascular disease and related dementia. While antiretroviral therapy (ART) reverses a number of complications of HIV, neuroimaging studies indicate chronic HIV is associated with CNS atrophy, and studies of antiretroviral CNS penetration aimed at defining the optimal “CNS ART” regimen have not translated into improved clinical outcomes.  This study aimed to quantify the excess risk of dementia conferred by infection with HIV.

This authors examined a cohort of 1114 veterans diagnosed with HIV who were at least 55 years of age seen in the VA system from 2004-2015, comparing them to 1114 propensity-matched controls. Matching was done based on age, sex, race, and substance use.  Cases and controls with evidence of dementia at baseline were excluded. Incident dementia during the study period (2004-2015) was identified based on ICD9 coding and was the primary outcome.

The study participants had a mean age of 63; 98% were men, 52% were non-Hispanic white, 38% non-Hispanic black, and 10% other races.  Common comorbidities included hypertension (34%), tobacco use (22%), alcohol or other drug use (18%), and diabetes (17%).  Compared to controls, cases lived in zip codes with higher educational attainment but lower median income.  Over a mean 5 years of followup, the rate of incident dementia was 5% in veterans with HIV versus 3% of the controls (p<0.01). Excluding the diagnosis of HIV-associated dementia, the distribution of dementia types was similar between groups. After accounting for age, sex, race, substance use, education, and income, having HIV was associated with a 50% increase in risk of dementia (95% CI 0.96-2.35).  Veterans with HIV were also more likely to die during followup (RR 1.7 with 95% CI 1.4-2). Veterans with HIV who received ART were more likely to be diagnosed with dementia than those who did not, but this association disappeared after adjustment for CD4 counts.  In subgroup analysis of veterans with HIV on various ART regimens, incident dementia did not vary with NNRTI-based vs non-NNRTI-based regimens (aHR 0.7 with 95% CI 0.4-1.4), though interestingly it trended toward greater rates in veterans on a regimen with vs without a NRTI backbone (aHR 1.8 with 95% CI 1-3.2).

So, these data indicate that HIV confers significantly increased risk of dementia in (mostly male) older adults, despite the use of ART – and in fact that dementia risk associated with ART was explained by more advanced HIV disease in veterans prescribed ART. 32701576

Can PLWH who have achieved virologic suppression on a dolutegravir and tenofovir-emtricitabine-based regimen safely switch to Biktarvy (BIC/TAF/FTC)?  I’m a little surprised anyone thought this needed an RTC, because bictegravir is as or more robust than dolutegravir in terms of resistance barrier, and the other drugs are the same.  But anyway, if you guessed yes, you’re right!  Loss of virologic suppression at a threshold of <50 copies/ml occurred in 0.4% of the switch group versus 1.1% of the continuation group, with no resistance development in either arm. 32668455

In the US, STI screening for MSM on PrEP is largely inadequate.  The CDC recommends comprehensive STI screening for MSM on PrEP every 3-6 months.  The authors used survey data from 2017-2019 about STI screening in MSM, stratified by PrEP use.  Of 3259 men who took the survey, 19% were on PrEP and 6% had used it in the past.  Of these, 87% reported consistent STI screening with blood tests and 78% with urine samples or urethral swabs, but only 57% and 64% for rectal and pharyngeal samples, respectively. Patients in the Southeast were less likely to receive consistent screening for urogenital (aPR 0.86) and rectal (aPR 0.76) STIs. 32702116