Engagement in health care in young people living with perinatal HIV

Evidence suggests that engagement in care (EIC) may be worse in young people with perinatal HIV (PHIV) than in adults or children living with HIV. However, there is no consensus on how best to measure EIC; and most studies use a simplistic definition based on number of clinic visits attended per year and examine limited predictors of EIC. In this thesis, I took an existing EIC algorithm for adults living with HIV in England, and adapted it to young people with PHIV in the Adolescent and Adults Living with Perinatal HIV cohort (AALPHI), using data from 2013-2015. A wide range of potential predictors of EIC from the AALPHI dataset were explored in logistic regression models (allowing for clustered data). Predictors of EIC identified in the quantitative analysis were then explored in focus groups with young people with PHIV to help contextualise the findings and to explore if they resonated with the experiences of young people themselves. Of 3,585 months of total follow-up in 306 young people, 3,126 (87%) person-months were classified as engaged in care. Multivariable predictors associated with poorer odds of being engaged in care were: baseline viral load >50c/mL vs. viral load ≤50c/mL; Asian/mixed ethnicity vs. black ethnicity; ever self-harmed vs. not; self-assessed adherence as bad/not so good/not on ART vs. good/excellent. Findings from the focus groups support and expand the quantitative results. Young people described actively choosing when to and when not to attend clinic depending on what they thought their viral load was or to hide non-adherence and self-harm. My adapted algorithm provides a more sensitive method to measure EIC in young people with PHIV. Identifying which young people are less likely to engage in care may allow targeted interventions to support young people to attend clinic and optimise their health outcomes. Findings from the focus groups provide a much broader understanding of the social meaning of EIC

Episodic medication adherence in adolescents and young adults with perinatally acquired HIV: a within-participants approach

Due to the success of antiretroviral (ART) medications, young people living with perinatally acquired HIV (PHIV+) are now surviving into adolescence and young adulthood. Understanding factors influencing ART non-adherence in this group is important in developing effective adherence interventions. Most studies of ART adherence in HIV-positive populations assess differences in adherence levels and adherence predictors between participants, over a period of time (global adherence). Many individuals living with HIV, however, including PHIV+ young people, take medication inconsistently. To investigate this pattern of adherence, a within-participants design, focussing on specific episodes of adherence and non-adherence, is suitable (episodic adherence). A within-participants design was used with 29 PHIV+ young people (17 female, median age 17 years, range 14–22 years), enrolled in the UK Adolescents and Adults Living with Perinatal HIV cohort study. Participants were eligible if they could identify one dose of medication taken and one dose they had missed in the previous two months. For each of the two episodes (one adherent, one non-adherent), behavioural factors (whom they were with, location, routine, day, reminders) and psychological factors at the time of the episode (information about medication, adherence motivation, perceived behavioural skills to adhere to medication – derived from the Information-Motivation-Behavioural Skills (IMB) Model – and affect) were assessed in a questionnaire. Non-adherence was significantly associated with weekend days (Friday to Sunday versus Monday to Thursday, p = .001), lack of routine (p = .004), and being out of the home (p = .003), but not with whom the young person was with or whether they were reminded to take medication. Non-adherence was associated with lower levels of behavioural skills (p < .001), and lower positive affect (p = .005). Non-adherence was not significantly associated with negative affect, information about ART, or ART motivation. The use of situationally specific strategies to enhance adherence in young people who take their medication inconsistently is proposed

Experiences of transition to adult care and readiness to self-manage care in young people with perinatal HIV in England

Background: There are few data on young people’s own experiences of transferring from paediatric to adult care, or readiness to self-manage care. Methods: A total of 132 young people living with perinatal HIV, aged 14–25 years, answered questions about transition experiences. Results: Of the participants, 45 (34%), with a median age of 16 (interquartile range [IQR] 16–17), were in paediatric care, of whom 89% reported that transition discussions had begun, at median age 15 (IQR 14–16) years. Young people in adult care were more likely than those in paediatric care to self manage appointments (90% vs 42% respectively, P < 0.001), and know their antiretroviral therapy (ART) drugs (55% vs 37%, P = 0.033). Knowledge of most recent CD4 T cell count/VL was slightly better for those in adult care (48% vs 31%, P = 0.059); naming side effects of ART was similar (71% vs 60%, P = 0.119). Conclusions: Transition discussions occurred before movement from paediatric to adult care. Further education around ART, potential side effects, and CD4 T cell count/viral load knowledge is required

Factors Associated With Nonadherence to Antiretroviral Therapy Among Young People Living With Perinatally Acquired HIV in England

Young people living with perinatally acquired HIV may be at risk of poor adherence to antiretroviral therapy; identification of predictors, using a conceptual framework approach proposed previously by others, is important to identify those at higher risk. In 261 young people with perinatally acquired HIV in England, 70 (27%) reported 3-day nonadherence, 82 (31%) last month nonadherence, and 106 (41%) nonadherence on either measure. Of those reporting nonadherence on both measures, 52% (23/44) had viral load of ,50 copies/ml, compared with 88% (127/145) of those reported being fully adherent. In multivariable analysis, young person and medication theme factors were associated with nonadherence. The main predictors of 3-day nonadherence were antiretroviral therapy containing a boosted protease inhibitor and poorer quality of life. Predictors of last month nonadherence were having told more people about one’s HIV status, worse self-perception about having HIV, and boosted protease inhibitor–based regimens. The consistency of individual young person and medication factors in predicting nonadherence gives insight into where interventions may best be targeted to improve adherence

Arterial Stiffness in a Cohort of Young People Living With Perinatal HIV and HIV Negative Young People in England

Background: Antiretroviral therapy (ART) has increased life expectancy and consequently the risk of cardiovascular disease (CVD) in adults living with HIV. We investigated the levels and predictors of arterial stiffness in young people (YP) living with perinatal HIV (PHIV) and HIV negative YP in the Adolescents and Adults Living with Perinatal HIV (AALPHI) study. Methods: AALPHI was a prospective study evaluating the impact of HIV infection and exposure to ART on YP living with PHIV (aged 13-21 years) who had known their HIV status for at least 6 months, and HIV negative YP (aged 13-23 years) who either had a sibling, friend or parent living with HIV. Participants were enrolled from HIV clinics and community services in England. Two hundred and thirteen PHIV and 65 HIV negative YP (42% siblings of PHIV) had pulse wave velocity (PWV) measurements taken (Vicorder software) from the supra-sternal notch to the middle of the thigh cuff, at their second interview in the study between 2015 and 2017. Average PWV was calculated from the three closest readings (≥3 and ≤ 12 m/s) within 0.6 m/s of each other. Linear regression examined predictors of higher (worse) PWV, including age, sex, HIV status and height as a priori, ethnicity, born outside UK/Ireland, alcohol/nicotine/drug use, weight, waist-to-hip-ratio, mean arterial pressure (MAP), caffeine 2 h before PWV and nicotine on day of PWV. A separate PHIV model included CD4, viral load, years taking ART and ART regimen. Findings: One hundred and twenty eight (60%) PHIV and 45 (69%) HIV negative YP were female (p = 0.18), with median (IQR) age 18 (16, 20) and 18 (16, 21) years (p = 0.48) respectively. Most PHIV were taking a combination of three ART drugs from two classes. There was a trend toward higher (worse) mean PWV in the PHIV group than the HIV negative group [unvariable analysis 6.15 (SD 0.83) m/s vs. 5.93 (0.70) m/s, respectively, unadjusted p = 0.058], which was statistically significant in the multivariable analysis [adjusted p (ap) = 0.020]. In multivariable analysis being male (ap = 0.002), older age (ap < 0.001), higher MAP (ap < 0.001) and nicotine use on day of measurement (ap = 0.001) were also predictors of higher PWV. The predictors were the same in the PHIV model. Interpretation: By late adolescence PHIV had worse PWV in comparison to HIV negative peers, and traditional risk factors for CVD (higher arterial pressure, being male and older age) were associated with higher PWV values. Regular detailed monitoring of cardiovascular risk factors should become standard of care for every young person with PHIV worldwide

Anxiety and depression symptoms in young people with perinatally acquired HIV and HIV affected young people in England

Adolescents with perinatal HIV (PHIV) may be at higher risk of anxiety and depression than HIV negative young people. We investigated the prevalence of symptoms of anxiety and depression in PHIV and HIV-affected (siblings of PHIV and/or had an HIV positive mother) young people in England. Symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) scores. A cross-sectional analysis was conducted of data from 283 young people with PHIV aged 13-21 years and 96 HIV-affected young people aged 13-23 years in the Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort. Linear regression investigated factors associated with higher (worse) anxiety and depression scores.115 (41%) and 29 (30%) PHIV and HIV-affected young people were male, median age was 16 [interquartile range 15,18] and 16 [14,18] years and 241 (85%) and 71 (74%) young people were black African, respectively. There were no differences in raw or z-scores of anxiety and depression, or self-esteem, between PHIV and HIV-affected participants (all p values >0.1). Across both PHIV and HIV-affected groups, factors associated with higher anxiety scores were having more carers in childhood, speaking a language other than English at home, lower self-esteem, and ever thinking life was not worth living and lower social functioning. Factors associated with higher depression scores were male sex, death of one or both parents, ever excluded from school, lower self-esteem and lower social functioning. This study found anxiety and depression scores were similar among PHIV and HIV-affected young people and similar to that of population norms. Other studies have found an association between poorer mental health and worse health outcomes in young people with PHIV, highlighting the need to identify young people at increased risk and provide timely support

2-loop Functional Renormalization Group Theory of the Depinning Transition

We construct the field theory which describes the universal properties of the quasi-static isotropic depinning transition for interfaces and elastic periodic systems at zero temperature, taking properly into account the non-analytic form of the dynamical action. This cures the inability of the 1-loop flow-equations to distinguish between statics and quasi-static depinning, and thus to account for the irreversibility of the latter. We prove two-loop renormalizability, obtain the 2-loop beta-function and show the generation of "irreversible" anomalous terms, originating from the non-analytic nature of the theory, which cause the statics and driven dynamics to differ at 2-loop order. We obtain the roughness exponent zeta and dynamical exponent z to order epsilon^2. This allows to test several previous conjectures made on the basis of the 1-loop result. First it demonstrates that random-field disorder does indeed attract all disorder of shorter range. It also shows that the conjecture zeta=epsilon/3 is incorrect, and allows to compute the violations, as zeta=epsilon/3 (1 + 0.14331 epsilon), epsilon=4-d. This solves a longstanding discrepancy with simulations. For long-range elasticity it yields zeta=epsilon/3 (1 + 0.39735 epsilon), epsilon=2-d (vs. the standard prediction zeta=1/3 for d=1), in reasonable agreement with the most recent simulations. The high value of zeta approximately 0.5 found in experiments both on the contact line depinning of liquid Helium and on slow crack fronts is discussed.Comment: 32 pages, 17 figures, revtex

Functional Renormalization Group and the Field Theory of Disordered Elastic Systems

We study elastic systems such as interfaces or lattices, pinned by quenched disorder. To escape triviality as a result of ``dimensional reduction'', we use the functional renormalization group. Difficulties arise in the calculation of the renormalization group functions beyond 1-loop order. Even worse, observables such as the 2-point correlation function exhibit the same problem already at 1-loop order. These difficulties are due to the non-analyticity of the renormalized disorder correlator at zero temperature, which is inherent to the physics beyond the Larkin length, characterized by many metastable states. As a result, 2-loop diagrams, which involve derivatives of the disorder correlator at the non-analytic point, are naively "ambiguous''. We examine several routes out of this dilemma, which lead to a unique renormalizable field-theory at 2-loop order. It is also the only theory consistent with the potentiality of the problem. The beta-function differs from previous work and the one at depinning by novel "anomalous terms''. For interfaces and random bond disorder we find a roughness exponent zeta = 0.20829804 epsilon + 0.006858 epsilon^2, epsilon = 4-d. For random field disorder we find zeta = epsilon/3 and compute universal amplitudes to order epsilon^2. For periodic systems we evaluate the universal amplitude of the 2-point function. We also clarify the dependence of universal amplitudes on the boundary conditions at large scale. All predictions are in good agreement with numerical and exact results, and an improvement over one loop. Finally we calculate higher correlation functions, which turn out to be equivalent to those at depinning to leading order in epsilon.Comment: 42 pages, 41 figure

Cognitive Function in Young Persons With and Without Perinatal HIV in the AALPHI Cohort in England: Role of Non-HIV-Related Factors

BACKGROUND:  There is limited evidence about the cognitive performance of older adolescents with perinatally acquired human immunodeficiency virus (HIV) compared with HIV-negative (HIV-) adolescents. METHODS:  A total of 296 perinatally HIV-infected (PHIV+) and 97 HIV- adolescents (aged 12-21 and 13-23 years, respectively) completed 12 tests covering 6 cognitive domains. The HIV- participants had PHIV+ siblings and/or an HIV-infected mother. Domain-specific and overall (NPZ-6) z scores were calculated for PHIV+ participants, with or without Centers for Disease Control and Prevention (CDC) stage C disease, and HIV- participants. Linear regression was performed to explore predictors of NPZ-6. RESULTS:  One hundred twenty-five (42%) of the PHIV+ and 31 (32%) of the HIV- participants were male; 251 (85%) and 69 (71%), respectively, were black African; and their median ages (interquartile range) were 16 (15-18) and 16 (14-18) years, respectively. In PHIV+ participants, 247 (86%) were receiving antiretroviral therapy, and 76 (26%) had a previous CDC C diagnosis. The mean (standard deviation) NPZ-6 score was -0.81 (0.99) in PHIV+ participants with a CDC C diagnosis (PHIV+/C), -0.45 (0.80) in those without a CDC C diagnosis (PHIV+/no C), and -0.32 (0.76) in HIV- participants (P < .001). After adjustment, there was no difference in NPZ-6 scores between PHIV+/no C and HIV- participants (adjusted coefficient, -0.01; 95% confidence interval, -.22 to .20). PHIV+/C participants scored below the HIV- group (adjusted coefficient, -0.44; -.70 to -.19). Older age predicted higher NPZ-6 scores, and black African ethnicity and worse depression predicted lower NPZ-6 scores. In a sensitivity analysis including PHIV+ participants only, no HIV-related factors apart from a CDC C diagnosis were associated with NPZ-6 scores. CONCLUSIONS:  Cognitive performance was similar between PHIV+/no C and HIV- participants and indicated relatively mild impairment compared with normative data. The true impact on day-to-day functioning needs further investigation