Elizabeth Lowenthal

Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges

Worldwide, more than three million children are infected with HIV, 90% of whom live in sub-Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children with HIV are reaching adolescence in large numbers. The growing population of adolescents with perinatally acquired HIV infection living within this region presents not only unprecedented challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review, we discuss the changing epidemiology of paediatric HIV and the particular features of HIV infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the immune system is not developed results in distinctive chronic clinical complications that cause severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual relationships, while undergoing rapid physical and psychological development. Context-specific strategies for early identification of HIV infection in children and prompt linkage to care need to be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health and psychological, educational, and social services. Health-care workers will need to be trained to recognise and manage the needs of these young people so that the increasing numbers of children surviving to adolescence can access quality care beyond specialist services at low-level health-care facilities.

Adolescent HIV disclosure in Zambia: barriers, facilitators and outcomes.

As adolescents living with HIV gain autonomy over their self‐care and begin to engage in sexual relationships, their experiences of being informed about their HIV status and of telling others about their HIV status may affect their ability to cope with having the disease.

Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children

IMPORTANCE Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. OBJECTIVE To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. MAIN OUTCOMES AND MEASURES The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. RESULTS With a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses. CONCLUSIONS AND RELEVANCE Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.

Rapid psychosocial function screening test identified treatment failure in HIV+ African youth

Abstract Psychosocial dysfunction in older children and adolescents is common and may lead to nonadherence to HIV treatments. Poor adherence leads to HIV treatment failure and the development of resistant virus. In resource-limited settings where treatment options are typically limited to only one or two available lines of therapy, identification of individuals at highest risk of failure before failure occurs is of critical importance. Rapid screening tools for psychosocial dysfunction may allow for identification of those children and adolescents who are most likely to benefit from limited psychosocial support services targeted at preventing HIV treatment failure. The Pediatric Symptom Checklist (PSC) is used in high resource settings for rapid identification of at-risk youth. In 692 HIV-infected treated children (ages of 8–< 17 years) in Botswana, having a high score on the PSC was associated with having virologic failure (OR 1.7, 95% CI: 1.1–2.6). The PSC may be a useful screening tool in pediatric HIV.

Postnatal infant HIV prophylaxis: a survey of U.S. practice.

For neonates identified as at increased risk of acquiring HIV perinatally, the optimal postnatal prophylaxis regimen is not known. Current United States Public Health Service guidelines recognize that combination postnatal prophylaxis may be considered in some situations but that there are little data regarding the effectiveness and safety of any postnatal regimen besides zidovudine. The actual use of combination postnatal regimens in the United States has not previously been described. We conducted a national, Web-based survey between December 2009 and January 2010 to describe the percent of providers who prescribe combination postnatal prophylaxis, the antiretroviral combinations they used, and the risk factors that might elicit combination postnatal prophylaxis. 472 known or possible perinatal HIV providers were queried; 42% (n = 197) responded and 68% of respondents (134) were eligible to complete the survey. Sixty-two percent (n = 83) of participating providers reported use or recommendation of combination postnatal prophylaxis in the last year. Three drugs, zidovudine, lamivudine and nevirapine, comprised 77% of first-choice combination regimens. Lopinivir-ritonivir (LPV/RTV) was included in 16% of all reported regimens. Combination postnatal prophylaxis was strongly preferred in patient-based scenarios with additional risk factors for perinatal HIV transmission.

Impact of the human immunodeficiency virus on early multidrug-resistant tuberculosis treatment outcomes in Botswana.

SETTING The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear. OBJECTIVE To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana. DESIGN Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs). RESULTS A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4). CONCLUSION We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.

Parental Absence From Clinic Predicts Human Immunodeficiency Virus Treatment Failure in Adolescents

It is estimated that more than 2.1 million adolescents (10–19 years of age) live with human immunodeficiency virus (HIV) in low-income and middle-income countries.1 When compared with both adults and younger children, HIV-infected adolescents have higher rates of nonadherence, virologic failure, and death.2,3 As they age, adolescents generally increase their health care–related autonomy. Adolescents may attend a clinic with or without an adult caregiver (parent). The relationship between parental attendance at clinic visits and adolescent chronic disease outcomes is unknown. We hypothesized that routine clinic attendance without a parent would be associated with the risk of HIV treatment failure, particularly in younger adolescents.

Risk Factors for Suboptimal Antiretroviral Therapy Adherence in HIV-Infected Adolescents in Gaborone, Botswana: A Pilot Cross-Sectional Study

Objective Little is known about factors associated with suboptimal antiretroviral treatment (ART) adherence among adolescents in Sub-Saharan Africa. Our objective was to determine the level of ART adherence and predictors of non-adherence among human immunodeficiency virus (HIV)-infected adolescents at the Botswana-Baylor Children’s Clinical Centre of Excellence in Gaborone, Botswana. Methods In a cross-sectional study, 82 HIV-infected adolescents receiving ART and their caregivers were administered a structured questionnaire. The patient’s clinical information was retrieved from medical records. Outcome measures included excellent pill count ART adherence (>95%) and virologic suppression (HIV viral load <400 copies/mL). Multivariate logistic regression analysis was performed to identify independent predictors of ART non-adherence. Results The overall median (interquartile range) ART adherence was 99% (96.5–100) (N = 82). Seventy-six percent of adolescents had excellent pill count ART adherence levels and 94% achieved virologic suppression. Male adolescents made up 65% of the non-adherent group (P = 0.02). Those who displayed suboptimal ART adherence were more likely to report having ever missed ART doses due to failure to pick up medication at the pharmacy (30.0% versus 9.7%, P = 0.03). In the multivariate logistic regression model, male sex (odds ratio [OR] 3.29, 95% confidence interval [CI] 1.13–9.54; P = 0.03) was the only factor which was independently associated with suboptimal ART adherence. Conclusions A high proportion of HIV-infected adolescents studied had excellent ART adherence and virologic suppression, with male adolescents at higher risk of suboptimal adherence than females. Further research to investigate how sex relates to suboptimal adherence may aid in the design of targeted intervention strategies.

Factors associated with self-reported adherence among adolescents on antiretroviral therapy in Zimbabwe

Nonadherence to medication is the key obstacle to human immunodeficiency virus (HIV) treatment success. The group at highest risk of nonadherence is adolescents, but relatively little is known about risk factors for and protective factors against poor adherence in this age group. We undertook a cross-sectional study of 262 HIV-infected adolescents aged 10–19 years on antiretroviral therapy at two clinics in Harare, Zimbabwe, to investigate personal and system-level factors associated with optimal self-reported adherence. Suboptimal adherence was common with only 101 (39%) reporting “excellent” adherence. Having the guardian present at each clinical encounter, comfort with asking questions to the health provider and participating in group sessions led by a professional facilitator were all significantly associated with excellent adherence (p < 0.05). Strengthening the parent–child dyad and professional-led groups as strategies to improve adherence should be evaluated.

Validation of the Pediatric Symptom Checklist in HIV-infected Batswana

Objective: To determine the validity of the Pediatric Symptom Checklist (PSC), a brief measure of psychosocial health, for screening HIV+ Batswana children. Method: Setswana versions of the parent and child PSC were administered to 509 HIV+ Batswana children (age 8–16) and their parents/guardians. Test properties were evaluated and cut-off scores were derived using receiver operating characteristic curve analysis. Scores on the parent-completed PSC and the child-completed PSC-Y were compared to parental and clinic staff reports of concern about the childs psychosocial health and to scores on the Childrens Depression Inventory and the Revised Childrens Manifest Anxiety Scale. Results: The Setswana PSC has high internal consistency (Cronbachs alpha 0.87 for the parent-completed version). Comparing PSC scores to parental reports of concern and child-reported depression symptoms, a cut-off score of 20 on the PSC and PSC-Y maximised the sensitivity and specificity. Conclusions: The PSC performed well in Setswana-speaking children and is a promising screening tool for paediatric psychosocial problems in busy clinical settings. Screening with the PSC may allow for early detection and treatment of psychosocial problems. This is likely to be of particular value for HIV+ children for whom HIV treatment non-adherence may result from untreated psychosocial dysfunction.