Assessing longitudinal patterns of depressive symptoms and the influence of symptom trajectories on HIV pre‐exposure prophylaxis adherence among adolescent girls in the HPTN 082 randomized controlled trial

Abstract

Introduction African adolescent girls and young women (AGYW) eligible for HIV pre‐exposure prophylaxis (PrEP) experience high levels of depressive symptoms. Depression can reduce PrEP adherence among adults, although analyses have considered depression as a time‐varying exposure rather than modelling distinct patterns of symptoms. The association between depressive symptoms and PrEP adherence has not been explored for AGYW. To address these gaps, we sought to understand depressive symptom trajectories among African AGYW initiating PrEP and the impact of time‐varying depressive symptoms and symptom trajectories on PrEP adherence. Methods HPTN 082 was an open‐label PrEP study among AGYW (ages 16 to 24) in Zimbabwe and South Africa from 2016 to 2018. Depressive symptoms were measured at enrolment and Weeks 13, 26 and 52, using the 10‐item Center for Epidemiologic Studies scale; a score ≥10 is indicative of elevated depressive symptoms. PrEP adherence was defined as any detectable tenofovir diphosphate (TFV‐DP) levels. Group‐based trajectory modelling was used to model longitudinal patterns of depressive symptoms. We assessed psychosocial and behavioural predictors of depressive symptom trajectory membership (e.g. PrEP stigma, intimate partner violence [IPV], sexual behaviour). We modelled associations between (1) group trajectory membership and PrEP adherence at Week 52 and (2) time‐varying depressive symptoms and PrEP adherence through follow‐up. Results At enrolment, 179 (41.9%) participants had elevated depressive symptoms. Group‐based trajectory models revealed persistent elevated depressive symptoms in 48.5%, declining symptoms in 9.4% and no consistent or mild depressive symptoms in 43.3%. AGYW who engaged in transactional sex, reported IPV, or had traumatic stress symptoms were more likely to be assigned to the persistent elevated symptom group compared with the consistent no/mild symptom group (Wald test p‐value all <0.01). Participants assigned to the persistent elevated depressive symptom trajectory had a significantly lower risk of detectable TFV‐DP at Week 52 than those in the no/mild symptom trajectory (adjusted prevalence ratio = 0.89; 95% CI: 0.80 to 0.98). Elevated depressive symptoms were significantly inversely associated with PrEP use throughout follow‐up (adjusted relative risk = 0.73; 95% CI = 0.53 to 0.99). Conclusions Persistent depressive symptoms were common among African AGYW seeking PrEP. Integration of depressive symptom screening and treatment into PrEP programmes may improve PrEP effectiveness among African women.

Having trust in the PrEP provider is crucial to more accurate self-reported adherence among South African and Zimbabwean adolescent girls and young women in the open- label HPTN 082 study

“…Finally, adherence goal setting was not captured at each visit to re ect the dynamic nature of the AGYW's sexual partnerships, which may be better aligned with patient-reported adherence. Goal setting recognizes AGYW's self-autonomy, which can facilitate open communication with providers, including identifying barriers such as depression experienced by AGYW [32].…”

“…CASI data, including HIV risk perception, sexual behavior, alcohol use, substance use, and depressive symptoms, were collected at enrollment and then quarterly for up to 12 months. A brief version (10-items) of the Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess depressive symptoms [31,32]. The question, 'How would you describe your chances of getting HIV in the next year' was dichotomized as perceived HIV risk in the next year if responses were small, moderate, great chance and prefer not to answer.…”

Exploring effects of multi-level factors on transitions of risk-taking behaviors among Bahamian middle-to-late adolescents

“…Studies for longitudinal patterns or trajectories, such as LTA, often require large datasets. Consistent with the literature, we used the entire sample to improve precision and statistical power and controlled for intervention assignment in our study (e.g., Berg et al, 2021; Velloza et al, 2021). Fourth, although assigning participants to different statuses based on highest posterior probabilities is a common approach in LTA (Clendennen et al, 2019; Mathur et al, 2014), it did not take into account classification uncertainty.…”

The importance of assessing and addressing mental health barriers to PrEP use during pregnancy and postpartum in sub‐Saharan Africa: state of the science and research priorities

“…Women who report IPV or depression have an increased risk of low PrEP adherence [ 47 , 48 , 49 , 50 , 51 ], and IPV‐related stress contributes to adherence challenges [ 47 ]. In an analysis of depression symptom trajectories among young women initiating PrEP, 48.5% had persistent elevated depression symptoms; these women were more likely to report IPV and less likely to have detectable TFV‐DP throughout follow‐up than participants with mild or no depression symptoms [ 65 ]. Although only IPV, post‐traumatic stress and depression have been linked to low PrEP adherence and persistence in the published literature, PPW with other mental health disorders and concerns—anxiety, suicidality and alcohol use disorder are common [ 66 , 67 , 68 ]—likely also face challenges to consistent PrEP use.…”