A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The purpose of this study was to examine health care providers’ experiences regarding the processes of disclosure and assent in pediatric HIV/AIDS patients. The study population included providers who were involved with the care of pediatric HIV/AIDS. A survey was distributed through email and asked questions to explore provider demographics, the average age of assent to treatment and research, the average age of disclosure of HIV, what factors determine the age of disclosure, barriers to disclosure, provider opinions, and provider perceptions of conflict within the disclosure process. While results showed that there are wide variations among individual patients and providers, most providers agree that disclosure should occur in older school age children (between ages 6-10 years), which is also the time that they typically are able to assent to treatment and clinical trials. Providers often agreed that there is a conflict between the ages of disclosure and assent. Parental concerns (fear of stigma, inappropriate disclosure, and personal guilt) were most often the reason for delays in the disclosure process. The disclosure process was felt to be most effective when done in a step-wise manner that includes multiple practitioners and counseling with families.

This study confirmed whether children on the current treatment of choice for HIV infection, Highly Active Antiretroviral Treatment (HAART), exhibit better immune functioning than children on earlier forms of treatment, including sole exposure to Monotherapy/Combination Therapy (Mono-Combo) and "upgrading" from Mono-Combo to HAART (Conversion). It explored whether HAART protects areas of neuropsychological functioning previously found to be compromised in children perinatally infected with HIV more effectively than these earlier treatments. This study includes a unique population (i.e., predominantly minority, low SES status, and largely bilingual), and controls for a number of treatment variables that have not been previously considered. Using the Neurodevelopmental Model and the literature, it was hypothesized that more global functions (i.e., IQ indices besides processing speed) and functions developing earlier in life (i.e., language) would be less affected than more specific functions developing later in life (i.e., visual-motor integration and processing speed). Treatment groups included Mono-Combo, Converters, and HAART. Participants (N=161, 3 to 20 years) were assessed in language, visual-motor integration, processing speed, and IQ using standardized measures and procedures. Three MANCOVAS and an ANCOVA compared groups on immune and neuropsychological measures using age antiretroviral medications were started and years on antiretroviral medications as covariates. Results showed children on HAART have significantly better immune functioning than the Mono-Combo and Converter groups. Consistent with other studies that have controlled for demographic factors, language functioning was not affected by treatment type. Contrary to expectations, visual-motor integration was also not affected by treatment type. Interestingly, Converters were found to perform worse on processing speed than children only exposed to Mono-Combo or HAART. Consistent with expectations, the other IQ indices (i.e., VCI, POI, and FDI) were not affected by treatment type. Findings support the use of HAART globally to improve immune functioning. However, they also provide evidence that HAART does not more effectively protect areas of neuropsychological functioning previously found to be compromised than these former treatments, even when controlling for agents that cross the blood brain barrier, age medications were started, and years on medications. They also bring into question the possible effect of frequency and timing of regimen changes.

This study is one of the only investigations to examine the complex inter-relationships between immune status, cognitive functioning, and disease progression in school-aged, perinatally infected, HIV+ children on HAART over time and is the first to conduct long-term follow-up assessments beyond one year after initiating HAART. Previous research has shown that HIV+ children on HAART show stability in cognitive functioning for up to one year. The current study investigated cognitive functioning, as measured by the Wechsler Intelligence Scale for Children -III, as a function of immune functioning and disease progression over time in this sample. Overall, results showed that PIQ scores remained stable over the three time points. However, further analyses demonstrated that poorer immune status, as measured by CD4% <25, at the first time point significantly predicted lower Performance IQ (PIQ)scores and PIQ subtest scores at the third time point, even after controlling for covariates. Similarly, additional analyses revealed that PIQ scores significantly declined over time as a function of CD4% category at the first time point. Finally, scores on the PIQ, Verbal IQ (VIQ), Coding, Picture Arrangement, Symbol Search, and Arithmetic at the first time point were all significant predictors of more advanced disease progression, as measured by CDC C classification at follow-up. The clinical relevance of this study and recommendations for future research in this area are discussed

Adherence to antiretroviral therapy (ART) is one of the most important issues in pediatric patients living with Human Immunodeficiency Virus (HIV). Combined with the fact that young patients face a large array of adherence barriers, interventions that can increase adherence are of great interest. Financial incentives (FIs) are a novel approach in pediatric HIV settings, and have not been studied previously in this disease for this age group. Thus, we sought to evaluate the effects FIs had in helping pediatric HIV patients achieve and maintain virologic suppression (VS). Furthermore, a post-incentive survey was administered to evaluate the self-perceived effects of FIs. In our study, FIs were not associated with achieving VS among pediatric and adolescent patients. The post-incentive survey has demonstrated many aspects of patients' and guardians' perceptions of FIs that should be considered in future FI studies. First, it was likely that patients who effectively grasped the concept of financial reward were most positively influenced by FIs. Second, the study data suggested that FIs may be contra-effective to those patients who report strong emotional responses to negative outcomes. Further and more comprehensive studies are required to fully characterize these effects.

Human immunodeficiency virus (HIV) is a virus that affects the body’s immune system (Centers for Disease Control [CDC], 2016a). HIV is a worldwide epidemic and disproportionately impacts youth in the United States. Youth living with HIV (YLWH) face significant mental health problems, namely depression, anxiety, and posttraumatic stress disorder (PTSD) with rates of these disorders discrepant from those in the general population. In addition to psychological difficulties, health literacy is another factor that influences individuals with HIV and is a priority of research with adolescents (Kalichman et al., 2000; Manganello, 2008). The National HIV/AIDS Strategy: Update 2020 (White House Office of National AIDS Policy, 2015) identified youth, ages 13 to 24 years, as a key population needing broad support not only for HIV prevention but also engagement in care including improving mental health and health literacy. The current study explored the extent to which YLWH were health literate in addition to the extent to which they exhibited psychological symptoms of depression, anxiety, and posttraumatic stress disorder. Furthermore, the study examined the extent to which health literacy and psychological symptoms were associated with health outcomes. A total of 145 YLWH between the ages of 13 and 25 years participated in the study. Participants completed the Center for Epidemiologic Studies Depression Scale (CES-D; Radloff, 1977), Generalized Anxiety Disorder-7 Item Scale (GAD-7; Spitzer, Kroenke, Williams, & Lowe, 2006), Primary Care-PTSD Screen (PC-PTSD; Prins et al., 2003), and Brief Estimate of Health Knowledge and Action-HIV Version (Osborn, Davis, Bailey, & Wolf, 2010). Of the 145 participants, 103 completed the CES-D, 144 completed the GAD-7, 131 completed the PC-PTSD, and 102 completed the BEHKA-HIV. In addition, participants’ biological markers of immune functioning (i.e., CD4 count and viral load) were obtained from medical abstraction. Results indicated the sample reported high levels of symptoms of depression, anxiety, and PTSD. Thirty-five percent of participants screened positive for depressive symptoms, 26% screened positive for anxiety symptoms, and 21% screened positive for PTSD symptoms. Participants had a moderate amount of HIV knowledge and the majority reported taking their medications under most conditions. Age was a significant predictor of CD4 count and viral load such that increasing age was associated with worse immune system functioning. Educational attainment was a significant predictor of CD4 count and to a lesser extent viral load indicating that greater education was associated with better immune system functioning. There was an interaction between mode of transmission and psychological symptoms. For perinatally infected youth, greater psychological symptoms were associated with a decline in CD4 count. The same decline was not seen for behaviorally infected youth. Health literacy (knowledge and action) added significantly to the explanation of the variance in viral load. Decreasing action scores were statistically associated with an increased likelihood of having a detectable viral load. These findings point to the need for prevention and intervention mental health services for YLWH. Future research should determine prevention and intervention strategies for mental health issues with YLWH in particular. Additionally, health literacy is an important factor that should be addressed by practitioners working with YLWH. More research needs to be conducted to determine the best way to measure health literacy in YLWH and how to intervene with improving health literacy.

Yes / Despite being a preventable disease, pediatric HIV infection continues to be a public health concern due to the morbidity and mortality associated with the disease. Vertical transmission of HIV occurs when a mother living with HIV passes the virus to her baby during pregnancy, childbirth, or breastfeeding. Globally, the vertical transmission rate of HIV is 9% with sub-Saharan Africa accounting for 90% of these infections. In Kenya, the national vertical transmission rates of HIV stood at 11.5% by the end of 2018, with a target to reduce vertical transmission rates to below 5% and 2% in breastfeeding and non-breastfeeding infants respectively, by the end of 2021. To determine the prognostic factors influencing HIV-free survival among infants enrolled for HIV early infant diagnosis (EID) services in selected hospitals in Nairobi County, Kenya. A prospective cohort study design was adopted. HIV exposed infants were recruited at six weeks to determine HIV-free survival over 12 months follow up. Simple random sampling was used to select 166 infants and data were collected from the mothers using semi-structured interviewer-administered questionnaires. Log-rank tests were used to test for associations at the bi-variable level while Cox-proportional regression was used to analyze data at the multi-variable level, with the aid of STATA 14 software. Ethical approval was obtained from Kenya Medical Research Institute, Scientific Ethics Review Unit. The overall infant HIV incidence rate over one-year follow-up was 9 cases per 100 person-years (95% CI: 5.465-16.290). The failure event was defined as an infant with a positive PCR test during the study period with total failures being 13 (9.41%) over 12 months. Prognostic factors associated with poor infant HIV-free survival were young maternal age (18-24 years) and mothers with a recent HIV diagnosis of ≤ 2 years since a positive HIV diagnosis (HR 5.97 CI: 1.20, 29.58) and (HR 6.97 CI: 1.96, 24.76), respectively. Maternal prognostic factors associated with poor infant HIV-free survival were young maternal age (18-24 years) and recent maternal HIV diagnosis of ≤ 2 years since positive HIV diagnosis. The study recommended the development of an intervention package with more rigorous adherence counseling and close monitoring for young mothers, and mothers with recent HIV diagnoses.

Chaque année 330 000 (dont 300 000 en Afrique) nouvelles infections à VIH surviennent chez les moins de quinze ans – majoritairement par un mécanisme de transmission verticale d’une mère infectée à son enfant. Pourtant, des interventions efficaces pour réduire la transmission mère-enfant (TME) existent mais ne sont pas toujours disponibles en pratique de routine pour les femmes qui en ont besoin. L’agenda international en cours vise une élimination de l’infection pédiatrique de VIH – et le maintien des mères en vie – à l’horizon 2015. A la lumière de la crise économique mondiale, il apparait opportun de pouvoir juger du montant de ressources nécessaires à la réalisation de cet objectif. Ce travail de thèse dresse le panorama du mode de délivrance des interventions pour la prévention de la TME (PTME) et de la prise en charge des enfants infectés par le VIH dans cinq pays à ressources limitées que sont la Chine, la Côte d’Ivoire, la Namibie, le Rwanda et l’Ukraine. Il apporte une estimation de leur coût et renseigne sur leur efficacité et leur caractère abordable. En outre, une estimation du coût de l’implémentation de potentiels scénarios de passage à échelle des interventions est apportée ; la mesure du nombre de cas (et de décès) non évités sur la période de projection permet de se rendre compte du coût de l’inaction. Enfin, sont discutés deux obstacles majeurs à la diffusion des services de PTME que sont le contexte politique ambiant et l’organisation de l’offre de soins (contrainte en ressources humaines qualifiées notamment). / A decade into the implementation of prevention of mother-to-child HIV transmission (PMTCT) programs, countries are making impressive progress towards fulfilling global commitments and achieving global goals. However, achieving a generation free from HIV will entail sustained effort and commitment in the coming years and estimating the cost of this work is fundamental. In light of the global economic downturn, reliable and up-to-date information on the costs of the dedicated services is needed to estimate the amount of additional resources required to scale up those services within the context of the Millennium Development Goals, and to assist resource-limited countries, external funders and multilateral agencies in planning, identify cost drivers and areas of potential savings. This work pursued the aims (1) to produce a reliable estimation of the costs associated with PMTCT services in five low- and middle-income countries, and (2) to ascertain the range and median unit costs needed for scaling up these services across a prevention, treatment and care continuum. Countries were selected given three key criteria related to their economic level and health spending, the national HIV epidemic status and typology, and the coverage of their maternal, neonatal and child health (MNCH) and PMTCT programs. Data were collected in Cote d’Ivoire, China, Namibia, Rwanda, and Ukraine using a health-care provider perspective from October 2009 to April 2010. In-country samples were designed to reflect publicly funded MNCH facilities that were delivering a define range of PMTCT and pediatric HIV services. The package includes HIV testing and counseling, male partner testing, CD4 testing, antiretroviral prophylaxis provision, community-based activities, HIV-exposed infant prophylaxis, and 2-year post-partum family planning. Additional information on prices and volume of services was collected from national government bodies, international donor partners, and non-governmental organizations. Cost data were then analyzed using a bottom-up approach of "micro-costing" where costs are calculated by identifying the actual resources used for each patient. Primary outcomes are costs per specific end-users and nation-wide total program costs, subdivided by major cost categories. After that, we simulated the expected costs over time according to a scale-up analysis estimating the costs needed to increase service coverage under various scenarios of coverage and antiretroviral protocols. These scenarios are incremental in their content: each subsequent scenario adds components and costs to the previous one. Future costs are discounted at a 3% rate. The affordability of each scenario (compared to the previous one) was concomitantly examined through the generation of incremental cost effectiveness ratios. The cost of inaction, measured in both terms of cases non-averted and deaths non-avoided throughout the scaling-up period, was ultimately assessed.