Predicting mortality within 1 year of ART initiation in children and adolescents living with HIV in sub-Saharan Africa: a retrospective observational cohort study.

BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV. METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria. FINDINGS: The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001). INTERPRETATION: This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings. FUNDING: National Institute of Health Fogarty International Center.

Estimating the risk of SARS-CoV-2 deaths using a Markov switching-volatility model combined with heavy-tailed distributions for South Africa.

BACKGROUND: SARS-CoV-2 (Covid-19 virus) infection exposed the unpreparedness of African countries to health-related issues, South Africa included. Africa recorded more than 211 853 deaths as a consequence of Covid-19. When rare and deadly diseases require urgent hospitalisation strikes, governments and healthcare providers are usually caught unprepared, resulting in huge loss of lives. Usually, at the beginning of such pandemics, there is no rich data for health practitioners and academics to be able to forecast the number of patients or deaths related to the pandemic. This study aims to predict the number of deaths associated with Covid-19 infection. With the availability of the number of deaths on a daily basis, the results stemming from this study are important to inform and plan health policy. METHODS: This study uses the daily number of deaths due to Covid-19 infection. Exploratory data analysis reveals that the data exhibits non-normality, three structural breaks and volatility clustering characteristics. The Markov switching (MS)-generalized autoregressive conditional heteroscedasticity (GARCH)-type model combined with heavy-tailed distributions is fitted to the returns of the data. Using available daily reported Covid-19-related deaths up until 26 August 2021, we report 10-day ahead forecasts of deaths. All forecasts are compared to the actual observed values in the forecasting period. RESULTS: The Anderson-Darling Goodness of fit test confirms that the fitted models are adequate for the data. The Kupiec likelihood ratio test and the root mean square error (RMSE) were used to select the robust model at different risk levels. At 95% the MS(3)-GARCH(1,1) combined with Pearson's type IV distribution (PIVD) is the best model. This indicates that the proposed best-fitting model is reasonable and can be used for predicting the daily number of deaths due to Covid-19. CONCLUSION: The MS(3)-GARCH(1,1)-PIVD model provides a reliable and accurate method for predicting the minimum number of death due to Covid-19. The accuracy of the proposed model will assist policymakers, academics and health practitioners in forecasting the volatility of future health-related deaths in which the predictability of volatility plays an integral role in health risk management.

A randomized controlled trial evaluating the effects of a family-centered HIV care model on viral suppression and retention in care of HIV-positive children in Eswatini.

INTRODUCTION: A family-centered care model (FCCM) providing family-based HIV services, rather than separate adult/pediatric services, has been proposed to increase pediatric retention and treatment adherence. MATERIALS AND METHODS: Eight health-care facilities in the Hhohho region of Eswatini were randomized to implement FCCM (n = 4) or continue standard-of-care (SOC) separate adult/pediatric clinics (n = 4). HIV-positive children and caregivers were enrolled; caregiver interview and child/caregiver chart abstraction were done at enrollment and every three months; pediatric viral load was evaluated at enrollment and every six months through 12 months. Because of study group differences in 12-month viral load data availability (89.4% FCCM and 72.0% SOC children had 12-month viral load), we used three separate analyses to evaluate the effects of FCCM on children's viral suppression (<1,000 copies/mL) and undetectable virus (<400 copies/mL) at 12 months. In the first analysis, all children with missing viral outcome data were excluded from the analysis (modified intent to treat, mITT). The second analysis used inverse probability of missingness weighted logistic regression to estimate the effect of FCCM on 12-month viral outcomes compared to SOC (weighted mITT). For the third approach, missing virologic outcome data were imputed as virologic failure (imputed ITT). We also examined factors associated with viral suppression at 12 months using multivariable logistic regression. RESULTS: We enrolled 379 HIV-positive children and 363 caregivers. Among all children at enrollment, viral suppression and undetectability was 78.4% and 73.9%, respectively, improving to 90.2% and 87.3% at 12 months. In mITT and weighted mITT analyses, there was no significant difference in children's 12-month viral suppression between FCCM and SOC groups (89.2% and 91.6%, respectively). Using imputed ITT, there was a modest increase in 12-month viral suppression in FCCM versus SOC children (79.7% and 69.8%, respectively, p = 0.051) and 12-month undetectability (78.7% and 65.7%, respectively, p = 0.015). Among the 255 children suppressed at enrollment, more FCCM versus SOC children (98.0% versus 95.3%) were suppressed at 12-months, but this was not statistically significant in mITT or weighted mITT analyses, with a marginally significant difference using imputed mITT analysis (p = 0.042). A higher proportion of children suppressed at enrollment had undetectable viral load at 12 months in FCCM versus SOC children (98.0% versus 92.5%), a statistically significant difference across analytical methods. Among the 61 children unsuppressed at enrollment, achieving suppression was higher among SOC versus FCCM children, but this difference was not statistically significant and included only 38 children; and there were no significant differences in detectable viral load at 12 months. There were no significant differences between study groups in retention or ART adherence at 12 months for children or caregivers. Factors associated with lack of viral suppression/detectability at 12 months included lack of viral suppression at enrollment and having a younger caregiver (age <25 years). CONCLUSIONS: FCCM in Eswatini was associated with a modest increase in viral suppression/undetectability at 12-months; 12-month retention and adherence did not differ by study group for children or caregivers. High levels of suppression and retention in both groups may have limited our ability to detect a difference. TRIAL REGISTRATION: NCT03397420; ClinicalTrials.gov.

Transition to Dolutegravir Is Associated With an Increase in the Rate of Body Mass Index Change in a Cohort of Virally Suppressed Adolescents.

BACKGROUND: Antiretroviral therapy (ART) regimens that contain dolutegravir (DTG) have been associated with increases in body mass index (BMI) in adults. However, this relationship has not been well described in adolescents. METHODS: In a retrospective observational cohort of 460 virally suppressed (<200 copies/mL) adolescents living with human immunodeficiency virus at a clinical site in Eswatini, body mass index (BMI) measurements were analyzed between 1 year prior to the transition to DTG and up to 1 year after DTG transition. Random-effects linear spline models were used to describe the rate of change in BMI before and after the transition to DTG. RESULTS: In adolescents, BMI increased at a rate of 0.3 kg/m2 per year before DTG transition and increased to a rate of 1.2 kg/m2 per year after DTG transition. Sex of the adolescent modified the relationship between DTG and rate of BMI change: BMI rate of change after DTG transition was increased by 1.1 kg/m2 in females and 0.6 kg/m2 per year in males. CONCLUSIONS: Transition to DTG in virally suppressed adolescents (aged 10-19 years) is associated with an increase in the rate of BMI change. Female adolescents may experience a larger change than males. Further investigation is required to elucidate the mechanism that underlies these observations and to assess how DTG impacts BMI in adolescents following longer durations of treatment.

'There are no more secrets': acceptability of a family-centered model of care for HIV positive children in Eswatini.

BACKGROUND: HIV-positive children have lagged adults on retention in HIV care and viral suppression. To address this gap, Eswatini's Ministry of Health started a pilot family-centered HIV care model (FCCM) targeting HIV-positive children under 20 years old and their families. METHODS: We conducted semi-structured in-depth interviews with 25 caregivers and 17 healthcare workers (HCWs) to assess acceptability of FCCM in four pilot FCCM health facilities in Hhohho region of Eswatini. Thematic analysis with inductive and deductive codes was used to identify salient themes. RESULTS: Caregivers and HCWs reported FCCM benefits including strengthening the family bond, encouragement for family members to disclose their HIV status and supporting each other in taking antiretroviral drugs. Caregivers reported that they spent fewer days in clinic, experienced shorter waiting times, and received better counseling services in FCCM compared to the standard-of-care services. FCCM implementation challenges included difficulty for families to attend clinic visits together (e.g., due to scheduling conflicts with weekend Teen Support Club meetings and weekday FCCM appointments). Both HCWs and caregivers mentioned difficulty in sharing sensitive health information in the presence of other family members. HCWs also had challenges with supporting caregivers to disclose HIV status to children and managing the larger group during clinic visits. CONCLUSIONS: FCCM for HIV-positive children was acceptable to both caregivers and HCWs, and they supported scaling-up FCCM implementation nationally. However, special considerations should be made to address the challenges experienced by participants in attending clinic visits together as a family in order to achieve the full benefits of FCCM for HIV positive children.

Predicting Sexually Transmitted Infections Among HIV+ Adolescents and Young Adults: A Novel Risk Score to Augment Syndromic Management in Eswatini.

BACKGROUND: Despite poor predictive power, syndromic screening is standard of care for diagnosing sexually transmitted infections (STIs) in low-resource, high HIV-burden settings. Predictive models may augment syndromic screening when diagnostic testing is not universally available for screening high-risk patient populations such as adolescents and young adults living with HIV. SETTING: Four hundred fifteen adolescents and young adults living with HIV, age 15-24 years, participated from 3 clinical sites in Eswatini, provided urine, sexual and medical history, and completed physical examination. METHODS: STI cases were defined by a positive Xpert result for Chlamydia trachomatis, Neisseria gonorrhea, or Trichomonas vaginalis. Features predictive of an STI were selected through Least Absolute Shrinkage and Selection Operator (LASSO) with 5-fold cross validation. Various model strategies were compared with parametric area under the Receiver Operator Curve (AUC) estimation and inferences were made with bootstrapped standard errors. RESULTS: Syndromic screening poorly predicted STIs [AUC 0.640 95% Confidence Interval (95% CI): 0.577 to 0.703]. A model considering 5 predictors (age group, sex, any sexual activity, not always using condoms (either self or partner), a partner who was 25 years or older, and horizontal or unknown mode of HIV acquisition) predicted STIs better than syndromic screening [AUC: 0.829 (95% CI: 0.774 to 0.885)] and was improved when the risk score was supplemented with leukocyte esterase (LE) testing [AUC: 0.883 (95% CI: 0.806 to 0.961)]. CONCLUSIONS: This simple predictive model, with or without leukocyte esterase testing, could improve STI diagnosis in HIV-positive adolescents and young adults in high burden settings through complementary use with syndromic screening and to guide patient selection for molecular STI diagnostic tests.

"The right time is just after birth": acceptability of point-of-care birth testing in Eswatini: qualitative results from infant caregivers, health care workers, and policymakers.

BACKGROUND: Testing for HIV at birth has the potential to identify infants infected in utero, and allows for the possibility of beginning treatment immediately after birth; point of care (POC) testing allows rapid return of results and faster initiation on treatment for positive infants. Eswatini piloted birth testing in three public maternities for over 2 years. METHODS: In order to assess the acceptability of POC birth testing in the pilot sites in Eswatini, interviews were held with caregivers of HIV-exposed infants who were offered birth testing (N = 28), health care workers (N = 14), and policymakers (N = 10). Participants were purposively sampled. Interviews were held in English or SiSwati, and transcribed in English. Transcripts were coded by line, and content analysis and constant comparison were used to identify key themes for each respondent type. RESULTS: Responses were categorized into: knowledge, experience, opinions, barriers and challenges, facilitators, and suggestions to improve POC birth testing. Preliminary findings reveal that point of care birth testing has been very well received but challenges were raised. Most caregivers appreciated testing the newborns at birth and getting results quickly, since it reduced anxiety of waiting for several weeks. However, having a favorable experience with testing was linked to having supportive and informed family members and receiving a negative result. Caregivers did not fully understand the need for blood draws as opposed to tests with saliva, and expressed the fears of seeing their newborns in pain. They were specifically grateful for supportive nursing staff who respected their confidentiality. Health care workers expressed strong support for the program but commented on the high demand for testing, increased workload, difficulty with errors in the testing machine itself, and struggles to implement the program without sufficient staffing, especially on evenings and weekends when phlebotomists were not available. Policymakers noted that there have been challenges within the program of losing mothers to follow up after they leave hospital, and recommended stronger linkages to community groups. CONCLUSIONS: There is strong support for scale-up of POC birth testing, but countries should consider ways to optimize staffing and manage demand.

The Cascade of Care From Routine Point-of-Care HIV Testing at Birth: Results From an 18-Months Pilot Program in Eswatini.

BACKGROUND: HIV testing at birth may improve early treatment, but concerns remain about feasibility and retention of infants in care. In 2017, point-of-care (POC) HIV birth testing was introduced into routine care at 3 high-volume maternity health facilities in Eswatini. METHODS: POC birth testing was offered to HIV-exposed infants (HEI) born at, or presenting to, 3 maternities within 3 days of birth. Data were collected from a project-specific EID test request form and routine registers on all tests conducted from August 1, 2017 to November 30, 2018, including retesting at 6-8 weeks for infants testing negative at birth and six-month retention in HIV care and viral load suppression among infants testing HIV-positive at birth. RESULTS: Of 4322 eligible HEI, 3311 (76.6%) were tested. Twenty-six HIV-infected infants were identified (positivity rate 0.8%) and 25 initiated on antiretroviral therapy (ART) (96.1%). The median time from sample collection to ART initiation was 20.50 days (IQR 14-45). Twenty-one (84%) ART-initiated infants were on ART at 6 months after initiation. Nineteen infants (90.5%) had viral load test information at 6 months and 16 (84.2%) were virally suppressed. Of 3126 HEI testing negative at birth, 3004 (96.1%) were linked to laboratory databases and 2744 (91.3%) were retested at 6-8 weeks, with 9 (0.3%) additional infants testing HIV-positive. CONCLUSIONS: Uptake of POC birth testing was high in Eswatini with low HIV positivity. Almost all infants identified HIV-positive at birth were initiated on ART, with high retention in care and viral suppression. Birth testing did not seem to significantly reduce subsequent 6-8-week testing.

Point-of-Care Testing to Guide Treatment and Estimate Risk Factors for Sexually Transmitted Infections in Adolescents and Young People With Human Immunodeficiency Virus in Eswatini.

BACKGROUND: The World Health Organization (WHO) estimates 127 million new cases of Chlamydia trachomatis (CT), 87 million new cases of Neisseria gonorrhea (NG), and 156 million new cases of Trichomonas vaginalis (TV) each year, which corresponds to 355 (219-606), 303 (216-468), and 243 (97.6-425) thousand disability-adjusted life-years. In low-resource settings, however, sexually transmitted infections (STIs) are treated syndromically and many individuals with asymptomatic infection may be missed, especially adolescents and young adults with human immunodeficiency virus (HIV). METHODS: We enrolled patients aged 15-24 with HIV (N = 300) attending a family-centered HIV clinic in Mbabane, Eswatini. Participants completed a sexual history questionnaire and provided urine as well as oropharyngeal and/or vaginal swabs, if sexually active, for testing with Xpert CT/NG and TV tests. Analysis included bivariate and multivariate odds ratios and test sensitivity and specificity. RESULTS: Sexually transmitted infection rates were highest (25.0%; 95% confidence interval [CI], 15.2-37.3) in females ages 20-24 who were ever sexually active. In patients with confirmed STIs, NG (15 of 32, 47%) was more common than CT (9 of 32, 28%) and TV (8 of 32, 25%). Syndromic screening alone had a sensitivity of 32.0% (95% CI, 14.9-53.3) and specificity of 86.0% (95% CI, 79.0-91.4) but varied by gender. The presence of an STI was associated with reporting new sexual partner(s) (OR = 2.6; 95% CI, 1.1-6.4), sometimes to never using condoms (OR = 4.2; 95% CI, 1.7-10.2), most recent sexual partner >25 years old (OR = 3.2; 95% CI, 1.3-7.9), and HIV diagnosis at age ≥15 years (OR = 3.4; 95% CI, 1.4-8.2). CONCLUSIONS: Syndromic screening alone performed poorly. Routine diagnostic testing significantly increases STI detection and should be considered in high-risk populations, such as adolescents and young adults with HIV.

Association of Antiretroviral Drug Regimen With Viral Suppression in HIV-positive Children on Antiretroviral Therapy in Eswatini.

BACKGROUND: Global pediatric treatment goals are for 90% of known children living with HIV to be on antiretroviral therapy (ART), with 90% having viral suppression. We used enrollment data from a study evaluating a family-centered HIV care program in Eswatini to describe the ART histories and virologic outcomes of enrolled children living with HIV and identify factors associated with viral suppression (<1000 RNA copies/mL) and undetectability (<400 RNA copies/mL). METHODS: Factors associated with viral suppression and undetectability were identified using Pearson χ for categorical variables and Wilcoxon rank sum tests for continuous variables. RESULTS: Three hundred seventy-seven children were enrolled, median age 8.5 years. Median age at HIV diagnosis was 2.1 years; at ART initiation, 2.6 years; and ART duration at enrollment, 4.1 years. Ninety-nine percent were receiving ART; 95.2% were on first-line ART and 4.8% on second-line ART. Most children (43.1%) were receiving nevirapine-based ART (median age 9.2 years), with 31.3% on lopinavir-ritonavir-based (median age 5.4 years) and 25.5%, efavirenz-based ART (median age 10.3 years). Viral suppression (<1000 copies/mL) was observed in 77.9% and undetectability (<400 copies/mL) in 73.5% of children. The only factor significantly associated with viral suppression was ART regimen, with 72.1% of children on nevirapine-based ART versus 86.7% on efavirenz-based ART virally suppressed. CONCLUSIONS: Although 99% of children enrolled in the study were receiving ART, viral suppression was observed in only 77.9%, with lowest rates among children receiving nevirapine-based ART. These findings highlight the critical importance of monitoring treatment regimen for optimizing treatment outcomes for pediatric HIV.

Barriers to antiretroviral therapy initiation for HIV-positive children aged 2-18 months in Swaziland.

Although early antiretroviral therapy (ART) reduces HIV-related mortality in children by up to 75%, almost half of HIV-positive children younger than 1 year old in Swaziland do not initiate ART. This study was conducted to identify barriers to early ART initiation among HIV-positive infants. This was a case-control study among HIV-positive infants, aged 2 to 18 months, who either did not initiate ART (cases), or initiated ART (controls), during 18 months after testing. Multivariable logistic regression showed that infants who visited the clinic every month, or every 2 months, were 5.78 and 6.20 times more likely to initiate ART than those who visited less often (OR 5.78, 95% CI 1.82-18.33 and OR 6.20, 95% CI 1.30-29.60 respectively). Children who lived ≤30 and 31-60 minutes from the nearest clinic were 84% and 79% less likely respectively to initiate ART (OR 0.16, 95% CI 0.03-0.78 and OR 0.21, 95% CI 0.04-0.98) compared with those who lived more than 60 minutes away. Children who received immunisation after 6 months were 22.59 times more likely to initiate ART (OR 22.59, 95% CI 7.00-21.72) than those who did not. Infants of caregivers who had excellent or good relationships with their healthcare provider were 4.32 times more likely to initiate ART (OR 4.32, 95% CI 1.01-18.59) than those of caregivers who had average or poor relationships with healthcare providers. The significant predictors of ART initiation identified in this study should be regarded as priority areas for intervention among HIV-positive women in Swaziland.

Characteristics of Treatment-experienced HIV-infected African Children and Adolescents Initiating Darunavir and/or Etravirine-based Antiretroviral Treatment.

BACKGROUND: Data are limited on the selection and sequencing of second-line and third-line pediatric antiretroviral treatment (ART) in resource-limited settings. This study aimed to evaluate characteristics of African pediatric patients initiated on darunavir (DRV) and/or etravirine (ETR) through a specific drug donation program. METHODS: This was a cross-sectional study of baseline immunologic, virologic and demographic characteristics of children and adolescents initiating DRV-based and/or ETR-based ART. Descriptive statistics were used. RESULTS: Study enrolled 48 patients (45.8% women; median age = 15 years [interquartile range 17.7-10.3]) at 9 clinical sites in Zambia, Swaziland, Kenya and Lesotho. The majority (87.5%; n = 42) had received ≥2 prior ART regimens; most (81.2%) had received lopinavir/ritonavir-based ART before switch. All patients had detectable HIV RNA (median = 56,653 copies/mL). Forty seven patients (98.9%) had HIV genotype results: 41 (87.2%) had ≥1 nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistance mutation (RM), predominantly M184V (76.6%; n = 36); 31 (65.9%) had ≥1 non-NRTI-RM, including 27 (57.4%) with ≥1 ETR-RM; 30 (63.8%) had ≥3 protease inhibitor RM, including 20 (42.6%) with ≥1 DRV-RM. For new ART regimens, DRV and raltegravir were most frequently prescribed (83.3%; n = 40 on DRV and raltegravir, each). Eighteen patients (37.5%) were initiated on the NRTI-sparing ART. CONCLUSIONS: In our study, a significant proportion of treatment-experienced African children and adolescents had one or more DRV-RM and ETR-RM. For the new regimen, more than a third of pediatric patients failing second-line ART were prescribed NRTI-sparing regimens. Better understanding of the current approaches to pediatric ART sequencing in resource-limited settings is needed.

Predictors of survival among HIV-positive children on ART in Swaziland.

The objective of the study was to determine predictors of survival among HIV-positive children (<15 years) in Swaziland. A retrospective cohort analysis of medical records for 4 167 children living with HIV who were initiated on antiretroviral therapy (ART) between 2004 and 2008, and followed up until 2014 was conducted in clinical settings at 36 health facilities. The Kaplan Meier Estimator, signed-ranks test, and the Cox proportional hazards regression model were applied to determine survival probabilities, significant difference among stratified survival functions and adjusted hazard ratios respectively. The results reveal that the median survival time for children was 78 months (95% CI: 77-79). Children who were initiated early on ART had higher survival probability over time (HR: 0.35 [95% CI: 0.21-0.57], p < 0.001) compared to those whose ART initiation was delayed. Children within the age group of <1 years had higher hazard (HR = 1.55 [95% CI: 1.16-2.08], p < 0.001) of death than children within the age group of 1-14 years. Children who were nourished had 88% lower hazard of death (HR: 0.12 [95% CI: 0.07-0.19], p < 0.001) than severely malnourished children. The study demonstrates that ART paediatric services are effective in increasing survival among HIV infected children and early initiated children have high survival probability. Active tuberculosis (TB), malnutrition, and delayed ART initiation remain predictors of poor survival among children living with HIV.

A qualitative analysis of the barriers to antiretroviral therapy initiation among children 2 to 18 months of age in Swaziland.

HIV/AIDS remains one of the leading causes of death among children under 5 years old in Swaziland. Although studies have shown that early initiation of infants and children diagnosed with HIV on antiretroviral therapy (ART) significantly reduces mortality, many children do not initiate ART until the later stages of disease. This study was designed to collect qualitative data from mothers and caregivers of HIV-positive children to identify the barriers to ART initiation. Focus group discussion (FGD) sessions were conducted in siSwati between July and September 2014 among caregivers of aged children 2-18 months in Swaziland who did or did not initiate ART between January 2011 and December 2012 after HIV DNA PCR-positive diagnosis of the infants. Denial, guilt, lack of knowledge, tuberculosis (TB)/HIV co-infection, HIV-related stigma, lack of money, and distance to clinics were reported by the participants as barriers to ART initiation. The findings further revealed that non-initiation on ART was not linked to a negative perception of the treatment. Findings suggest a need to improve sensitivity among healthcare workers as well as education and counselling services that will facilitate the ART initiation process.

Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis.

BACKGROUND: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited. METHODS: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance. Deidentified demographic and clinical data were used to explore risk factors associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. RESULTS: Among the 1450 genotypes analyzed, 1048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1 or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI resistance was particularly high in children exposed to ARV drugs through PMTCT; adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only. CONCLUSIONS: Protease inhibitor-based regimens in children aged <3 years are currently recommended by WHO, but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.

Predictors of survival among HIV-positive children on ART in Swaziland

The objective of the study was to determine predictors of survival among HIV-positive children (<15 years) in Swaziland. A retrospective cohort analysis of medical records for 4 167 children living with HIV who were initiated on antiretroviral therapy (ART) between 2004 and 2008, and followed up until 2014 was conducted in clinical settings at 36 health facilities. The Kaplan Meier Estimator, signed-ranks test, and the Cox proportional hazards regression model were applied to determine survival probabilities, significant difference among stratified survival functions and adjusted hazard ratios respectively. The results reveal that the median survival time for children was 78 months (95% CI: 77­79). Children who were initiated early on ART had higher survival probability over time (HR: 0.35 [95% CI: 0.21­0.57], p < 0.001) compared to those whose ART initiation was delayed. Children within the age group of <1 years had higher hazard (HR = 1.55 [95% CI: 1.16­2.08], p < 0.001) of death than children within the age group of 1­14 years. Children who were nourished had 88% lower hazard of death (HR: 0.12 [95% CI: 0.07­0.19], p < 0.001) than severely malnourished children. The study demonstrates that ART paediatric services are effective in increasing survival among HIV infected children and early initiated children have high survival probability. Active tuberculosis (TB), malnutrition, and delayed ART initiation remain predictors of poor survival among children living with HIV

A qualitative analysis of the barriers to antiretroviral therapy initiation among children 2 to 18 months of age in Swaziland

HIV/AIDS remains one of the leading causes of death among children under 5 years old in Swaziland. Although studies have shown that early initiation of infants and children diagnosed with HIV on antiretroviral therapy (ART) significantly reduces mortality, many children do not initiate ART until the later stages of disease. This study was designed to collect qualitative data from mothers and caregivers of HIV-positive children to identify the barriers to ART initiation. Focus group discussion (FGD) sessions were conducted in siSwati between July and September 2014 among caregivers of aged children 2­18 months in Swaziland who did or did not initiate ART between January 2011 and December 2012 after HIV DNA PCR-positive diagnosis of the infants. Denial, guilt, lack of knowledge, tuberculosis (TB)/HIV co-infection, HIV-related stigma, lack of money, and distance to clinics were reported by the participants as barriers to ART initiation. The findings further revealed that non-initiation on ART was not linked to a negative perception of the treatment. Findings suggest a need to improve sensitivity among healthcare workers as well as education and counselling services that will facilitate the ART initiation process