Dorothy E. Dow

Evaluating mental health difficulties and associated outcomes among HIV-positive adolescents in Tanzania.

ABSTRACT AIDS-related mortality among HIV-positive adolescents has risen by 50% despite the scale up of antiretroviral therapy (ART). ART maladherence likely plays a role in the increase of AIDS-related deaths among adolescents and has shown to be associated with psychosocial and mental health difficulties. Addressing the specific mental health needs of HIV-positive adolescents is critical to ending the HIV epidemic. This cross-sectional study prospectively enrolled HIV-positive adolescents (12–24 years) in Moshi, Tanzania. A structured questionnaire was administered that included questions about home, school, adherence, and measures of stigma (Berger Stigma Scale) and mental health. Mental health measures included depression (Patient Health Questionnaire-9), emotional/behavioral difficulties (Strengths and Difficulties Questionnaire), and traumatic experiences/post-traumatic stress symptoms (The University of California Los Angeles-post-traumatic stress disorder-Reaction Index). Mental health difficulties were prevalent among HIV-positive adolescents and were associated with incomplete adherence and stigma. Resources are needed to reduce HIV stigma and address mental health among HIV-positive adolescents in low-resource settings. This will improve not only mental health, but may also improve ART adherence and virologic suppression, improving overall health of the individual and reducing the risk of HIV transmission to others.

Risk factors influencing antibody responses to kaposi's sarcoma-associated herpesvirus latent and lytic antigens in patients under antiretroviral therapy

Background:Kaposis sarcoma-associated herpesvirus (KSHV) seropositivity and lytic antibody titer are predictors for Kaposis sarcoma. Methods:We examined demographic, viral, and immunologic factors that influence KSHV latent and lytic antibodies in HIV-infected patients. Results:Detection rate of KSHV latent but not lytic antibodies was lower in patients with CD4 cells/mm3 less than 200 than greater than 200 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.11-0.61) and CD8 cells/mm3 less than 400 than greater than 400 (OR, 0.26; 95% CI, 0.07-0.67). Overall seropositivity rate was higher in patients with CD4 cells/mm3 less than 200 than greater than 200 (OR, 2.34; 95% CI, 1.37-4.02) and HIV copies/mL greater than 400 than less than 400 (OR, 1.70; 95% CI, 1.09-2.65). Lytic antibody level was inversely correlated with CD4 count (P < 0.001). Lytic seropositivity (OR, 2.47; 95% CI, 1.35-4.50) and antibody level (adjusted difference mean optical density, 0.324; 95% CI, 0.16-0.46) were higher in patients with HIV infection greater than 15 than less than 15 years. Hispanics had higher lytic seropositivity rate (OR, 1.71; 95% CI, 1.07-2.73) and antibody level (adjusted difference mean optical density, 0.111; 95% CI, 0.03-0.18) than non-Hispanics. Conclusions:Lower CD4 and CD8 counts impair antibody response to KSHV latent antigens. Immune deterioration, long-term HIV infection, and Hispanic status are risk factors for Kaposis sarcoma predictors.

Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up

BackgroundIn Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up.MethodsThis was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained.Results161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01).ConclusionsAfter viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

Low rates of child testing for HIV persist in a high-risk area of East Africa.

Children in low- and middle-income countries (LMIC) are the least touched by recent successes in the diagnosis and treatment of HIV/AIDS globally. Early treatment is essential for a childs longer and higher quality of life; however, by 2011, only a small proportion of HIV-seropositive children in LMIC countries were receiving treatment, in part because of persisting low rates of diagnosis. This study of the prevalence and characteristics of children tested for HIV was embedded in the Coping with HIV/AIDS in Tanzania (CHAT) study in which HIV-seropositive and HIV-seronegative adults, and adults with unknown HIV status were asked about HIV testing for their children. Data were gathered from November 2009 to August 2010 during the scale-up of Prevention of Mother To Child Transmission and Early Infant Diagnosis programs in the region. Reports on 1776 children indicate that 31.7% of all children were reported to have been tested, including only 42.9% of children with an HIV-seropositive caregiver. In general, children more likely to be HIV tested were biological children of study participants, younger, of widowed adults, living in urban areas, and of HIV-seropositive parents/caregivers. Children belonging to the two indigenous tribes, Chagga and Pare, were more likely to be tested than those from other tribes. Rates of testing among children less than two years old were low, even for the HIV-seropositive caregiver group. The persistence of low testing rates is discussed in terms of the accessibility and acceptability of child testing in resource poor settings.

A Review of Human Herpesvirus 8, the Kaposi's Sarcoma-Associated Herpesvirus, in the Pediatric Population

Human herpesvirus 8 (HHV-8), also known as Kaposis sarcoma (KS)-associated herpesvirus, is the etiologic agent responsible for all types of KS. Although the majority of pediatric KS cases occur in sub-Saharan Africa, a rise in pediatric transplant KS has been reported in developed countries. In addition, HHV-8 is increasingly described as an infectious cause of hemophagocytic lymphohistiocytosis in children. Transmission of HHV-8 among children is poorly understood; however, the literature strongly suggests that horizontal transmission plays a critical role. Acute infection with HHV-8 and progression to KS in children may be different than in adults, and diagnosis may be overlooked. Currently, neither adult nor pediatric treatment guidelines exist. This review provides an overview of HHV-8 disease in children as it relates to epidemic KS, transplant KS, and other disease manifestations. The current state of the literature is reviewed and knowledge gaps are identified for future exploration.

Progress in the Prevention of Mother to Child Transmission of HIV in Three Regions of Tanzania: A Retrospective Analysis

Background Mother to child transmission (MTCT) of HIV-1 remains an important problem in sub-Saharan Africa where most new pediatric HIV-1 infections occur. Early infant diagnosis of HIV-1 using dried blood spot (DBS) PCR among exposed infants provides an opportunity to assess current MTCT rates. Methods We conducted a retrospective data analysis on mother-infant pairs from all PMTCT programs in three regions of northern Tanzania to determine MTCT rates from 2008–2010. Records of 3,016 mother-infant pairs were assessed to determine early transmission among HIV-exposed infants in the first 75 days of life. Results Of 2,266 evaluable infants in our cohort, 143 had a positive DBS PCR result at ≤75 days of life, for an overall transmission rate of 6.3%. Transmission decreased substantially over the period of study as more effective regimens became available. Transmission rates were tightly correlated to maternal regimen: 14.9% (9.5, 20.3) of infants became infected when women received no therapy; 8.8% (6.9, 10.7) and 3.6% (2.4, 4.8) became infected when women received single-dose nevirapine (sdNVP) or combination prophylaxis, respectively; the lowest MTCT rates occurred when women were on HAART, with 2.1% transmission (0.3, 3.9). Treatment regimens changed dramatically over the study period, with an increase in combination prophylaxis and a decrease in the use of sdNVP. Uptake of DBS PCR more than tripled over the period of study for the three regions surveyed. Conclusions Our study demonstrates significant reductions in MTCT of HIV-1 in three regions of Tanzania coincident with increased use of more effective PMTCT interventions. The changes we demonstrate for the period of 2008–2010 occurred prior to major changes in WHO PMTCT guidelines.

A Qualitative Exploration of the Mental Health and Psychosocial Contexts of HIV-Positive Adolescents in Tanzania.

Although 85% of HIV-positive adolescents reside in sub-Saharan Africa, little is known about the psychosocial and mental health factors affecting their daily well-being. Identifying these contextual variables is key to development of culturally appropriate and effective interventions for this understudied and high-risk population. The purpose of this study was to identify salient psychosocial and mental health challenges confronted by HIV-positive youth in a resource-poor Tanzanian setting. A total of 24 qualitative interviews were conducted with a convenience sample of adolescents aged 12–24 receiving outpatient HIV care at a medical center in Moshi, Tanzania. All interviews were audio-recorded, transcribed, and coded using thematic analysis. Psychosocial challenges identified included loss of one or more parents, chronic domestic abuse, financial stressors restricting access to medical care and education, and high levels of internalized and community stigma among peers and other social contacts. Over half of youth (56%) reported difficulties coming to terms with their HIV diagnosis and espoused related feelings of self-blame. These findings highlight the urgent need to develop culturally proficient programs aimed at helping adolescents cope with these manifold challenges. Results from this study guided the development of Sauti ya Vijana (The Voice of Youth), a 10-session group mental health intervention designed to address the psychosocial and mental health needs of HIV-positive Tanzanian youth.

Adherence to antiretroviral therapy among HIV-infected children receiving care at Kilimanjaro Christian Medical Centre (KCMC), Northern Tanzania: A cross- sectional analytical study

Introduction Paediatric adherence to Highly Active Antiretroviral Therapy (HAART) is a dynamic process involving many factors. Adherence for the majority on therapy matters to prevent failure of 1st and 2st line therapy. The purpose of this study was to determine the rate of adherence to antiretroviral therapy in HIV infected children. Methods We conducted a cross-sectional hospital based analytical study, from October 2011 to April 2012. HIV-infected children aged 2 to 17 years who had been on treatment for at least six months were enrolled. Data were collected by a standard questionnaire. Two-day self-report, one month self-recall report, and pill count were used to assess adherence. Results One hundred and eighty three respondents participated in this research. There were 92 (51%) males and 91 (49%) females. Only 45 (24.6%) had good adherence to their drug regimen when subjected to all three methods of assessment. Males were more adherent to ART than females (OR= 2.26, CI 1.05-4.87, p = 0.04). Adherence was worse among children who developed ART side effects (OR= 0.19, CI 0.07- 0.56;p = 0.01), could not attend clinic on regular basis (OR= 3.4, CI 1.60- 7.36, p = 0.01) and missed drug doses in the six months period prior to interview (OR= 0.40, CI 0.18-0.82, p= 0.01). Conclusion Only 24.6% of paediatric patients had good adherence to ART when subjected to all three measures. Drug side-effects, missing drug doses in the six months period prior to study start, monthly income and affording transportation to the clinicwere strong predictors of adherence.

Caregiver role in HIV medication adherence among HIV-infected orphans in Tanzania

ABSTRACT Youth living with HIV in sub-Saharan Africa face numerous challenges in adhering to HIV treatment. The AIDS epidemic has left many of these youth orphaned due to AIDS-related death of one or both parents. It is imperative to understand the family context of youth living with HIV in order to develop responsive interventions to improve adherence to antiretroviral therapy. We conducted qualitative in-depth interviews with 17 HIV-infected AIDS orphans, ages 13–24 years, screened positive for mental health difficulties according to the Patient Health Questionaire-9 (PHQ-9) or UCLA PTSD Reaction Index (PTSD-RI), and receiving outpatient HIV care at an adolescent medical clinic in Moshi, Tanzania. Treatment-related support varied by orphan status. Paternal orphans cared for by their biological mothers and maternal orphans cared for by grandmothers described adherence support such as assistance taking medication and attending clinic. Double orphans did not report adherence support. Several maternal and double orphans faced direct interference from caregivers and household members when they attempted to take their medications. Caregivers play a significant role in treatment adherence and must be considered in interventions to increase medication adherence in HIV-infected orphans. Findings from this study informed caregiver participation in Sauti ya Vijana (The Voice of Youth), a mental health intervention for youth living with HIV in Tanzania.

Providing Safe and Effective Preventative Antiretroviral Prophylaxis to HIV-exposed Newborns via a Novel Drug Delivery System in Tanzania.

Background: In developing countries, antiretroviral therapy provides life-saving treatment to HIV-positive women and their children before, during and after birth. However, supply chain challenges such as long distances, medication shortages and nonfacility deliveries often compromise consistent access to prophylactic treatment for at-risk infants. A proposed intervention to address these challenges, often referred to as the “Pratt Pouch,” allows for liquid-formulation medications, such as nevirapine (NVP), to be repackaged into single-dose pouches. These pouches are distributed antenatally. Methods: HIV-positive women at Kilimanjaro Christian Medical Centre in Moshi, Tanzania received 14 pouches each containing a single dose of NVP for prevention of mother-to-child transmission. Women were trained on how to open the pouch and dispense the medication to their infants after delivery. All participating women were asked to return to Kilimanjaro Christian Medical Centre 7–14 days after delivery, where infant blood spots were collected to assess NVP levels. Results: All enrolled women (21/21) administered NVP to their infants within 24 hours of birth. All enrolled infants (22/22) had NVP blood concentrations over 100 ng/mL and exhibited no health concerns attributable to over or under dosing. Conclusions: The Pratt Pouch intervention provides a clinically appropriate solution for addressing liquid-formulation antiretroviral access challenges in developing countries.