Missing HIV prevention opportunities in South African children – A 7-year review

CITATION: Feucht, U. D., Meyer, A., & Kruger, M. 2014. Missing HIV prevention opportunities in South African children – A 7-year review. BMC Public Health, 14:1265, doi:10.1186/1471-2458-14-1265.The original publication is available at http://bmcpublichealth.biomedcentral.comBackground: The prevention of mother-to-child transmission (PMTCT) program in South Africa is now successful in ensuring HIV-free survival for most HIV-exposed children, but gaps in PMTCT coverage remain. The study objective was to identify missed opportunities for prevention of mother-to-child transmission of HIV using the four PMTCT stages outlined in National Guidelines. Methods: This descriptive study enrolled HIV-exposed children who were below the age of 7 years and therefore born during the South African PMTCT era. The study site was in Gauteng, South Africa and enrolment was from June 2009 to May 2010. The clinical history was obtained through a structured caregiver interview and review of medical records and included socio-demographic data, medical history, HIV interventions, infant feeding information and HIV results. The study group was divided into the “single dose nevirapine” (“sdNVP”) and “dual-therapy” (nevirapine & zidovudine) groups due to PMTCT program change in February 2008, with subsequent comparison between the groups regarding PMTCT steps during the preconception stage, antenatal care, labor and delivery and postpartum care. Results: Two-hundred-and-one HIV-exposed children were enrolled: 137 (68%) children were HIV infected and 64 (32%) were HIV uninfected. All children were born between 2002 and 2009, with 78 (39%) in the “sdNVP” and 123 (61%) in the “dual-therapy” groups. The results demonstrate significant improvements in antenatal HIV testing and PMTCT enrolment, known maternal HIV diagnosis at delivery, mother-infant antiretroviral interventions, infant HIV-diagnosis and cotrimoxazole prophylaxis. Missed opportunities without improvement include pre-conceptual HIV-services and family planning, tuberculosis screening, HIV disclosure, psychosocial support and postnatal care. Not receiving consistent infant feeding messaging was the only PMTCT component that worsened over time. Conclusions: Multiple missed opportunities for optimal PMTCT were identified, which collectively increase children’s risk of HIV acquisition. Although HIV-testing and antiretroviral interventions improved, all PMTCT components need to be optimized to reach the goal of total pediatric HIV elimination.http://bmcpublichealth.biomedcentral.com/articles/10.1186/1471-2458-14-1265Publisher's versio

Recommendations for the medical evaluation of children prior to adoption in South Africa

The current legislative framework in South Africa (SA) supports adoption as the preferred form of care for children with inadequate or no parental or family support. There are an estimated 3.8 million orphans in SA, with approximately 1.5 - 2 million children considered adoptable. As a means of improving services, newly drafted adoption guidelines from the National Department of Social Development will in future require both non-profit and private sector adoption agencies to obtain a medical report on a child prior to placement. However, no local guidelines specify what an appropriate medical examination entails or how it should be reported. For the purposes of proposing and developing such guidelines, an open forum was convened at the Institute of Pathology, University of Pretoria, in March 2013. These ‘Recommendations for the medical evaluation of children prior to adoption in South Africa’ emanate from this meeting

Persistent Chlamydia trachomatis, Neisseria gonorrhoeae or Trichomonas vaginalis positivity after treatment among human immunodeficiency virus-infected pregnant women, South Africa

The objective of this study is to assess the predictors and frequency of persistent sexually transmitted infection (STI) positivity in human immunodeficiency virus (HIV)-infected pregnant women treated for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) or Trichomonas vaginalis (TV) infection. We enrolled HIV-infected pregnant women attending their first antenatal care visit and tested them for urogenital CT, NG and TV infection using Xpert® CT/NG and TV assays (Cepheid, Sunnyvale, CA). Those testing positive were treated. Participants either notified partners to seek treatment or were given extra medication to deliver to partners for treatment. Repeat testing was conducted approximately 21 days post-treatment or treatment initiation. Among 427 participants, 172 (40.3%) tested positive for any STI. Of the 136 (79.1%) that returned for repeat testing, 36 (26.5%) tested positive for the same organism: CT = 27 (26.5%), NG = 1 (6.3%), TV = 11 (16.7%). Persistent CT positivity was independently associated with having more than one sex partner in the preceding 12 months (adjusted-prevalence ratio [aPR] = 3.03, 95% CI: 1.44–6.37) and being newly diagnosed with HIV infection during the first antenatal care visit compared to those currently on antiretroviral therapy (aPR = 3.97, 95% CI: 1.09–14.43). Persistent TV positivity was associated with not knowing if a partner sought treatment following STI disclosure (aPR = 12.6, 95% CI: 2.16–73.5) and prior diagnosis of HIV but not currently on antiretroviral therapy. (aPR = 4.14; 95% CI: 1.25–13.79). We identified a high proportion of HIV-infected pregnant women with persistent CT or TV positivity after treatment. To decrease the risk of re-infection, enhanced strategies for partner treatment programmes are needed to improve the effectiveness of STI screening and treatment in pregnancy. The relationship between not being on antiretroviral therapy and persistent STI positivity needs further study.The Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health (NIH), award R21HD084274 and the President’s Emergency Plan for AIDS Relief through the United States Agency of the Cooperative Agreement AID 674-A-12-00017 funded this study. Noah Kojima was supported by the U.S. NIH Fogarty International Center (award number D43TW009343) and the University of California Global Health Institute. Christina A Muzny was supported by K23AI106957-01A1 from the National Institute of Allergy and Infectious Diseases.https://journals.sagepub.com/home/stdhj2021Medical MicrobiologyPaediatrics and Child Healt

Immune and Metabolic Alterations in Children with Perinatal HIV Exposure

With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children who are HIV-exposed-but-uninfected (CHEU) are now well recognized as having persistent health disparities compared to children who are HIV-unexposed–and-uninfected (CHUU). Differences reported between these two groups include immune dysfunction and higher levels of inflammation, cognitive and metabolic abnormalities, as well as increased morbidity and mortality in CHEU. The reasons for these disparities remain largely unknown. The present review focuses on a proposed link between immunometabolic aberrations and clinical pathologies observed in the rapidly expanding CHEU population. By drawing attention, firstly, to the significance of the immune and metabolic alterations observed in these children, and secondly, the impact of their healthcare requirements, particularly in low- and middle-income countries, this review aims to sensitize healthcare workers and policymakers about the long-term risks of in utero exposure to HIV and ART

Immune and Metabolic Alterations in Children with Perinatal HIV Exposure

With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children who are HIV-exposed-but-uninfected (CHEU) are now well recognized as having persistent health disparities compared to children who are HIV-unexposed–and-uninfected (CHUU). Differences reported between these two groups include immune dysfunction and higher levels of inflammation, cognitive and metabolic abnormalities, as well as increased morbidity and mortality in CHEU. The reasons for these disparities remain largely unknown. The present review focuses on a proposed link between immunometabolic aberrations and clinical pathologies observed in the rapidly expanding CHEU population. By drawing attention, firstly, to the significance of the immune and metabolic alterations observed in these children, and secondly, the impact of their healthcare requirements, particularly in low- and middle-income countries, this review aims to sensitize healthcare workers and policymakers about the long-term risks of in utero exposure to HIV and ART

INTEGRATED GROWTH ASSESSMENT IN THE FIRST 1000 DAYS OF LIFE: AN INTERDISCIPLINARY CONCEPTUAL FRAMEWORK

ABSTRACT Objectives: Prenatal growth affects short- and long-term morbidity, mortality and growth, yet communication between prenatal and postnatal healthcare teams is often minimal. This paper aims to develop an integrated, interdisciplinary framework for foetal/ infant growth assessment, contributing to continuity of care across the first 1000 days of life. Design: A multidisciplinary think-tank met regularly over many months to share and debate their practice and research experience related to foetal/ infant growth assessment. Participants’ personal practice and knowledge was verified against and supplemented by published research. Setting: Online and in-person brainstorming sessions of growth assessment practices that are feasible and valuable in resource-limited, low- and middle-income country (LMIC) settings. Participants: A group of obstetricians, paediatricians, dietitians/ nutritionists, and a statistician. Results: Numerous measurements, indices and indicators were identified for growth assessment in the first 1000 days. Relationships between foetal, neonatal and infant measurements were elucidated and integrated in an interdisciplinary framework. Practices relevant to LMICs were then highlighted: antenatal Doppler screening, comprehensive and accurate birth anthropometry (including proportionality of weight, length and head circumference), placenta weighing, and incorporation of length-for-age, weight-for-length and mid-upper arm circumference in routine growth monitoring. The need for appropriate, standardised clinical records and corresponding policies to guide clinical practice and facilitate interdisciplinary communication over time became apparent. Conclusions: Clearer communication between prenatal, perinatal and postnatal health care providers, within the framework of a common understanding of growth assessment and a supportive policy environment, is a prerequisite to continuity of care and optimal health and development outcomes

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa.

Limited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors.Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis.The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033).Major protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed

Early diagnosis is critical to ensure good outcomes in HIV-infected children: outlining barriers to care

HIV-infected children require early initiation of antiretroviral therapy (ART) to ensure good outcomes. The aim was to investigate missed opportunities in childhood HIV diagnosis leading to delayed ART initiation. Baseline data was reviewed of all children aged <15 years referred over a one-year period for ART initiation to the Kalafong Hospital HIV services in Gauteng, South Africa. Of the 250 children, one quarter (24.5%) were of school-going age, 34.5% in the preschool group, 18% between 6-12 months old and 23% below six months of age (median age=1.5 years [IQR 0.5- 4.8]). Most children (82%) presented with advanced/severe HIV disease, particularly those aged 6-12 months (95%). Malnutrition was prominent and referrals were mostly from hospital inpatient services (61%). A structured caregiver interview was conducted in a subgroup, with detailed review of medical records and HIV results. The majority (≥89%) of the 65 interviewed caregivers reported good access to routine healthcare, except for postnatal care (26%). Maternal HIV-testing was mostly done during the 2nd & 3rd pregnancy trimesters (69%). Maternal non-disclosure of HIV status was common (63%) and 83% of mothers reported a lack of psychosocial support. Routine infant HIV-testing was not done in 66%, and inadequate reporting on patient-held records (Road-to- Health Cards/Booklets) occurred frequently (74%). Children with symptomatic HIV disease were not investigated at primary healthcare in 53%, and in 68% of families the siblings were not tested. One-third of children (35%) had a previous HIV diagnosis, with 77% of caregivers aware of these prior results, while 50% acknowledged failing to attend ART-services despite referral. In conclusion, a clear strategy on paediatric HIV case finding, especially at primary healthcare, is vital. Multiple barriers need to be overcome in the HIV care pathway to reach high uptake of services, of which especially maternal reasons for not attending paediatric ART services need further exploration.http://www.tandfonline.com/loi/caic202016-08-30hb201

Comparison of projected susceptibility to antiretroviral medication in children with and without major protease inhibitor (PI) drug resistance mutations.

<p>Data collected from 65¹ and 64² patients respectively</p><p>Predicted drug susceptibility categories were determined through the Stanford HIVdb Algorithm</p><p><b>Abbreviations:</b> PI = protease inhibitors; LPV/r = ritonavir-boosted lopinavir; DRV/r = ritonavir-boosted darunavir; TPV/r = ritonavir-boosted tipranavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; EFV = efavirenz; ETR = etravirine; NRTI = nucleoside reverse transcriptase inhibitor; ABC = abacavir; AZT = zidovudine; d4T = stavudine; TDF = tenofovir; 3TC = lamivudine</p><p>Comparison of projected susceptibility to antiretroviral medication in children with and without major protease inhibitor (PI) drug resistance mutations.</p

Univariate analysis comparing patients with and without major protease inhibitor (PI) drug resistance mutations.

<p>Data collected from 65¹, 61², 60³, 59⁴, 28⁵, 43⁶, 40⁷, 42⁸ and 64⁹ patients respectively</p><p><b>Abbreviations:</b> ART = antiretroviral therapy; PI = protease inhibitors; IQR = interquartile range; BMI = body mass index; CD4 = CD4+ T-cell count in cells/mm³; CD4% = CD4 percentage; VL = HIV viral load; LDL = lower than detectable level; Nr = number; TB = tuberculosis; Ref = reference value; RTV-sPI = ritonavir as full-dose single protease inhibitor; ddLPV/r = double-dose boosted lopinavir; LPV/R⁺ = super-boosted lopinavir; NRTI = nucleoside reverse transcriptase inhibitor; TAMs = thymidine analogue mutations; NNRTI = non-nucleoside reverse transcriptase inhibitor</p><p>*From first failure time point (using LDL cut-off & >6 months on ART) to date of genotype</p><p>**Age- and sex-adjusted anthropometry according to WHO growth standards [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133452#pone.0133452.ref022" target="_blank">22</a>]</p><p>#Corresponding p-value for VL<1000 = 0.036</p><p>Univariate analysis comparing patients with and without major protease inhibitor (PI) drug resistance mutations.</p