Sorting Adherence Risk Factors to Shape Better Adherence Care

September 22, 2017

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Turning Adherence Research Into Clinical Action

Most findings on factors tied to good or bad adherence bear out a priori intuition. Social support,21,28 more education,9,25 and provider satisfaction21 favor good adherence. Alcohol and other substance use,12,14,16-24 food insecurity,30,31 and concerns about ART21,24 foster poor adherence. But research on adherence correlates comes laden with nuance and sprinkled with surprise. The second paragraph of this article sampled contradictory findings related to adherence and age, employment, comedications, and CD4 count. The rest of this article spotlights some fine points clinicians can use to shape clinical adherence strategies.

Adherence Drops After Delivery

Studies of pregnant women in the United States5,8,19 and an international meta-analysis52 agree that antiretroviral adherence during pregnancy drops 10% to 25% after delivery. In the bustle of perinatal and postnatal concerns, even clinicians well aware of this adherence threat may miss the opportunity to prevent a clinically meaningful slip in pill taking. With 14 of 51 studies in the meta-analysis coming from the United States, this study found that a 75.7% pooled prevalence of better than 80% adherence before delivery dropped to 53% postpartum (P = 0.005).52 Barriers to adherence included depression; physical, economic, and emotional stress; alcohol or drug use; and antiretroviral dosing frequency.

A US Pediatric ACTG study involved 519 women, 75% of whom reported perfect adherence (no missed doses in preceding 4 day) during pregnancy.5 Six, 24, and 48 weeks after delivery, the perfect adherence rate dipped to 65%, 64%, and 66% (P < 0.01). Among 149 women in ACTG protocol A5084, 57% reported adherence during pregnancy (no missed doses in past 3 months), and that rate dropped to 45% in the first 12 postpartum weeks (P = 0.03).19 Multivariate analysis determined that women who ever used illicit drugs had almost 6-fold higher odds of nonadherence (P = 0.002), and those who missed prenatal vitamins had almost 5-fold higher odds (P = 0.001). The latter finding suggests vitamin taking during pregnancy may offer a signal of antiretroviral adherence after delivery. In a US Women and Infants Transmission Study of 309 women, the self-reported complete adherence rate fell from 61% during pregnancy to 44% postpartum.8 More health-related symptoms and alcohol use emerged as independent predictors of nonadherence before and after delivery.

Adherence may be better during pregnancy because women want to protect their infant from HIV and because frequent monitoring during pregnancy can promote adherence (Table 3). After delivery, the HIV transmission motivation declines for nonbreastfeeding women, while they confront new demands in caring for an infant and often face postpartum depression. US Department of Health and Human Services (DHHS) guidelines for pregnant women with HIV caution, however, that adherence may also falter during the first trimester because of the nausea and vomiting common during that phase of pregnancy.53 These guidelines recommend more frequent viral load monitoring during pregnancy if adherence is a concern, and they endorse a protease inhibitor over an integrase inhibitor for women at risk of stopping therapy after delivery. For the same reason, switching from twice- to once-daily dosing could make sense.

Table 3. Reasons for Better Adherence During Pregnancy Than Postpartum
  • More frequent monitoring/adherence reinforcement during pregnancy
  • Mother's desire to protect fetus/neonate from HIV
  • Refraining from drug/alcohol use during pregnancy
  • Postpartum challenges in caring for infant
  • Postpartum physiologic changes/health challenges
  • Postpartum depression

"Because the immediate postpartum period poses unique challenges to antiretroviral adherence," the DHHS experts counsel, "arrangements for new or continued supportive services should be made before hospital discharge."53

Depression Undermines Adherence

The well-appreciated link between depression and wavering adherence in people with HIV rests on data from three meta-analyses14,21,44 and countless smaller studies. Meta-analysis of 207 studies presented from 1996 through 2014 determined that depression trailed only current substance use and concerns about ART in predicting poor adherence (Figure 2), but depression had a much greater negative impact than HIV stigma, protease inhibitor therapy, dosing frequency, financial constraints, or pill burden.21

Ranked Predictors of Poor Adherence

Ranked Predictors of Poor Adherence

Figure 2. Meta-analysis of 207 studies involving 103,836 people with HIV ranked depressive symptoms as the third strongest independent predictor of poor adherence, with effect size calculated as standard mean difference (SMD).21

(PI, protease inhibitor.)

A 111-study meta-analysis involving 43,366 HIV-positive people found no difference in depression prevalence by country income group.44 Overall chances of attaining at least 80% adherence was 42% lower in people with depressive symptoms (pooled OR 0.58, 95% CI 0.55 to 0.62), and that association did not differ by country income group, study design, or adherence rate.

Depression and Adherence in Youth

Adherence poses a sterner challenge to HIV-positive youth than to older or younger age groups. And depression may play a big part youth's inconsistent pill taking. A 125-study meta-analysis of 17,061 adults, 856 adolescents, and 1099 children found that similar proportions of adults (15.5%) and children (15.1%) self-reported depression as an adherence barrier, rates well below the 25.7% of adolescents attributing poor adherence to depression.14

A US Adolescent Trials Network analysis of 956 minority HIV-positive 16- to 24-year-olds found that 39% of them reported taking fewer than 90% of antiretrovirals in the past 7 days.22 Path analysis determined that higher self-efficacy (belief in one's ability to do something) predicted good adherence, while psychological symptoms (measured on the Brief Symptom Inventory) predicted lower self-efficacy, more substance use, and lower adherence (P < 0.01). A longitudinal study of 294 US youngsters 6 to 17 years old found that 38% had at least one psychiatric condition at the baseline visit.26 Multivariable logistic regression determined that youngsters with depression had 4-fold higher odds of missing more than 5% of doses in the past 3 days at follow-up week 96 (aOR 4.14, 95% CI 1.11 to 15.42).

Treating Depression Improves Adherence

If depression promotes poor adherence, one would expect that treating depression improves adherence. That doesn't always happen, learned US researchers who randomized 304 HIV-positive people with major depressive disorder to antidepressant therapy or usual care.54 After 12 months, lack of improvement in pill count-based adherence with versus without therapy, the authors suggest, could reflect high baseline adherence rates in both study groups (about 86%).

But a clutch of other recent studies, including one meta-analysis55 and one systematic review,56 did find that treating depression improves adherence in people with HIV. The meta-analysis considered 29 studies published between 2001 and 2012 involving antidepressant therapy, cognitive behavioral therapy, and mixed approaches.55 Meta-analysis indicated that odds of antiretroviral adherence were 83% better (standardized OR 1.83, 95% CI 1.27 to 2.55) in people treated for depression or psychological distress than in untreated people. In 17 intervention studies, people randomized to the intervention arm versus the control arm had twice high odds of improvement in depressive symptoms (standardized OR 2.07, 95% CI 1.38 to 3.30). Longer treatment yielded greater adherence rates than shorter treatments (random effects r = 0.43, P = 0.02). The systematic review found that 7 of 9 studies produced evidence that antidepressant treatment improved antiretroviral adherence.56

In a study of 7034 antiretroviral-treated Medicaid recipients, 66% were black, 47% experienced depression during the study period, and 32% had optimal adherence, defined as at least 90% adherence by prescription refill.10 Multivariate logistic regression determined that black participants had 30% lower odds of optimal adherence (aOR 0.70, 95% CI 0.63 to 0.78), while antidepressant therapy nearly doubled chances of optimal adherence (aOR 1.92, 95% CI 1.12 to 3.29).

Retrospective analysis of 3359 HIV-positive people in the Kaiser Permanente healthcare system in 8 states used medical records to determine that 1398 (42%) had a depression diagnosis, yet only 508 of these 1398 (36%) had a prescription for a selective serotonin reuptake inhibitor (SSRI).57 Chances of at least 90% antiretroviral adherence (determined by pharmacy refills) were almost 20% lower in people with depression not treated by SSRIs than in people without depression (aOR 0.81, 95% CI 0.70 to 0.98, P = 0.03). But chances of at least 90% antiretroviral adherence did not differ significantly between people without depression and (1) people with depression and prescribed an SSRI (aOR 0.91, 95% CI 0.72 to 1.15) or (2) people with depression and greater than 80% adherence to an SSRI (aOR 1.13, 95% CI 0.86 to 1.49).

US depression researchers calculated that only 48% of HIV-positive people with major depressive disorder get recognized clinically, only 18% get treated, only 7% get treated adequately, and only 5% achieve remission through treatment.58 See the Summer 2016 issue of RITA for a detailed review of depression in people with HIV.

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This article was provided by The Center for AIDS Information & Advocacy. It is a part of the publication Research Initiative/Treatment Action!. Visit CFA's website to find out more about their activities and publications.

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