Factors Associated With Severe Illness in Patients Aged <21 Years Hospitalized for COVID-19.

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness. METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 United States children's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation. RESULTS: Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5 to 11 (PR 3.72), and 12 to 17 years (PR 3.19). CONCLUSIONS: Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5 to 17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19.

Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021.

During June 2021, the highly transmissible† B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021.§ As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years,¶ and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021.†† Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19.§§ Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection¶¶ (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions.

Lost to follow-up: failure to engage children in care in the first three months of diagnosis.

Loss to follow-up (LTFU) is a critical factor in determining clinical outcomes in HIV treatment programs. Identifying modifiable factors of LTFU is fundamental for designing effective patient-retention interventions. We analyzed factors contributing to children LTFU from a treatment program to identify those that can be modified. A case-control study involving 313 children was used to compare the sociodemographic and clinical characteristics of children LTFU (cases) with those remaining in care (controls) at a large pediatric HIV care setting in Botswana. We traced children through caregiver contacts and those we found, we conducted structured interviews with patients' caregivers. Children <5 years were nearly twice as likely as older children to be LTFU (57·8% versus 30·9%, p <0 .01). Approximately half (47·6%, n = 51) of LTFU patients failed to further engage in care after just one clinic visit, as compared to less than 1% (n = 2) in the control group (p < 0.01). Children LTFU were more likely than controls to have advanced disease, greater immunosuppression, and not to be receiving antiretroviral therapy. Among interviewed patient caregivers, psychosocial factors (e.g., stigma, religious beliefs, child rebellion, disclosure of HIV status) were characteristics of patients LTFU, but not of controls. Socioeconomic factors (e.g., lack of transportation, school-related activities, forgetting appointments) were cited predominantly by the controls. Pediatric patients and their caregivers need to be targeted and engaged at their initial clinic visit, with special attention to children <5 years. Possible interventions include providing psychosocial support for issues that deter patients from engaging with The Clinic. Collaboration with community-based organizations focused on reducing stigma may be useful in addressing these complex issues.

The Pediatric AIDS Corps: a 5-year evaluation.

BACKGROUND: The Baylor College of Medicine International Pediatric AIDS Initiative at Texas Children's Hospital created a global health corps named the Pediatric AIDS Corps (PAC) in June 2005. This report provides descriptive details and outputs for PAC over its first 5 years. METHODS: Demographic data were gathered about PAC physicians employed from July 2006 to June 2011. A 21-question survey was used to query PAC physicians about their experiences in the program. Data concerning clinical experiences and educational programs also were reviewed. RESULTS: A total of 128 physicians were employed with PAC. The median duration served was 22.7 months. Eighty-seven percent indicated that experience affected their future career choice, with half continuing to work with children and families living in resource-limited areas after they left PAC. Patient care was identified as the most rewarding part of their work (73%), whereas deaths (27%) were the most difficult. Baylor College of Medicine International Pediatric AIDS Initiative enrollment of HIV-infected children and adolescents into care and treatment increased from 6107 to 103 731 with the addition of PAC physicians. Approximately 500 local health care professionals per quarter benefited from HIV clinical attachments that were not available before PAC arrival. PAC physicians visited outreach sites providing in-depth HIV mentoring of local health care professionals, leading to 37% of the sites becoming self-sufficient. CONCLUSIONS: The positive evaluation by the PAC and the scale-up of clinical and educational programs support the recent calls for the development of a national global health corps program.

Routine inpatient provider-initiated HIV testing in Malawi, compared with client-initiated community-based testing, identifies younger children at higher risk of early mortality.

OBJECTIVE: To determine how routine inpatient provider-initiated HIV testing differs from traditional community-based client-initiated testing with respect to clinical characteristics of children identified and outcomes of outpatient HIV care. DESIGN: Prospective observational cohort. METHODS: Routine clinical data were collected from children identified as HIV-infected by either testing modality in Lilongwe, Malawi, in 2008. After 1 year of outpatient HIV care at the Baylor College of Medicine Clinical Center of Excellence, outcomes were assessed. RESULTS: Of 742 newly identified HIV-infected children enrolling into outpatient HIV care, 20.9% were identified by routine inpatient HIV testing. Compared with community-identified children, hospital-identified patients were younger (median 25.0 vs 53.5 months), with more severe disease (22.2% vs 7.8% WHO stage IV). Of 466 children with known outcomes, 15.0% died within the first year of HIV care; median time to death was 15.0 weeks for community-identified children vs 6.0 weeks for hospital-identified children. The strongest predictors of early mortality were severe malnutrition (hazard ratio, 4.3; 95% confidence interval, 2.2-8.3), moderate malnutrition (hazard ratio, 3.2; confidence interval, 1.6-6.6), age < 12 months (hazard ratio, 3.2; 95% confidence interval, 1.4-7.2), age 12 to 24 months (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7), and WHO stage IV (hazard ratio, 2.2; 95% confidence interval, 1.1-4.6). After controlling for other variables, hospital identification did not independently predict mortality. CONCLUSIONS: Routine inpatient HIV testing identifies a subset of younger HIV-infected children with more severe, rapidly progressing disease that traditional community-based testing modalities are currently missing.

Nine-year follow-up of HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir-containing highly active antiretroviral therapy.

INTRODUCTION: Many Romanian children were infected nosocomially with human immunodeficiency virus (HIV) in the late 1980s. The Romanian-American Children's Center of Excellence in Constanta continues to follow approximately 450 of these patients. In 2001, 414 of these patients were initiated on triple therapy including lopinavir/ritonavir. Data from this cohort treated through August 2006 were published in April 2007 demonstrating that the treatment was well tolerated, with 337 children (81%) remaining on therapy after a median duration of >4 years. The current article describes the results of continued analysis of this cohort through end 2010. The objective of the study was to determine the long-term clinical outcomes of children and adolescents commenced on antiretroviral therapy (ART) including lopinavir/ritonavir. METHODS: Data were extracted retrospectively from the charts of the 336 patients remaining on lopinavir/ritonavir in August 2006. The following outcomes were analyzed: mortality, current patient status, viral load (VL), CD4 counts and reasons for discontinuation of lopinavir/ritonavir. RESULTS: The median age at initiation of lopinavir/ritonavir was 14.0 years (range 5.4 to 20.0 years). The median time on lopinavir/ritonavir treatment was 7.5 years (interquartile range 5.7 to 8.6 years). Overall mortality was 13.5%. Of the original 414 patients started on lopinavir/ritonavir in 2001, 199 (48.1%) remained on this therapy at the end of 2010 and of these 63.8% had undetectable viral load. CONCLUSION: Despite initial suboptimal ART, a significant proportion of patients subsequently treated with a lopinavir/ritonavir based regimen remained on this therapy for up to nine years.

Mortality and clinical outcomes in HIV-infected children on antiretroviral therapy in Malawi, Lesotho, and Swaziland.

OBJECTIVE: To determine mortality and immune status improvement in HIV-infected pediatric patients on antiretroviral treatment (ART) in Malawi, Lesotho, and Swaziland. METHODS: We conducted a retrospective cohort study of patients aged <12 years at ART initiation at 3 sites in sub-Saharan Africa between 2004 and 2009. Twelve-month and overall mortality were estimated, and factors associated with mortality and immune status improvement were evaluated. RESULTS: Included in the study were 2306 patients with an average follow-up time on ART of 2.3 years (interquartile range 1.5-3.1 years). One hundred four patients (4.5%) died, 9.0% were lost to follow-up, and 1.3% discontinued ART. Of the 104 deaths, 77.9% occurred in the first year of treatment with a 12-month mortality rate of 3.5%. The overall mortality rate was 2.25 deaths/100 person-years (95% confidence interval [CI] 1.84-2.71). Increased 12-month mortality was associated with younger age; <6 months (hazard ratio [HR] = 8.11, CI 4.51-14.58), 6 to <12 months (HR = 3.43, CI 1.96-6.02), and 12 to <36 months (HR = 1.92, CI 1.16-3.19), and World Health Organization stage IV (HR = 4.35, CI 2.19-8.67). Immune status improvement at 12 months was less likely in patients with advanced disease and age <12 months. CONCLUSIONS: Despite challenges associated with pediatric ART in developing countries, low mortality and good treatment outcomes can be achieved. However, outcomes are worse in younger patients and those with advanced disease at the time of ART initiation, highlighting the importance of early diagnosis and treatment.

The Tingathe programme: a pilot intervention using community health workers to create a continuum of care in the prevention of mother to child transmission of HIV (PMTCT) cascade of services in Malawi.

INTRODUCTION: Loss to follow-up is a major challenge in the prevention of mother to child transmission of HIV (PMTCT) programme in Malawi with reported loss to follow-up of greater than 70%. Tingathe-PMTCT is a pilot intervention that utilizes dedicated community health workers (CHWs) to create a complete continuum of care within the PMTCT cascade, improving service utilization and retention of mothers and infants. We describe the impact of the intervention on longitudinal care starting with diagnosis of the mother at antenatal care (ANC) through final diagnosis of the infant. METHODS: PMTCT service utilization, programme retention and outcomes were evaluated for pregnant women living with HIV and their exposed infants enrolled in the Tingathe-PMTCT programme between March 2009 and March 2011. Multivariate logistic regression was done to evaluate maternal factors associated with failure to complete the cascade. RESULTS: Over 24 months, 1688 pregnant women living with HIV were enrolled. Median maternal age was 27 years (IQR, 23.8 to 30.8); 333 (19.7%) were already on ART. Among the remaining women, 1328/1355 (98%) received a CD4 test, with 1243/1328 (93.6%) receiving results. Of the 499 eligible for ART, 363 (72.8%) were successfully initiated. Prior to, delivery there were 93 (5.7%) maternal/foetal deaths, 137 (8.1%) women transferred/moved, 51 (3.0%) were lost and 58 (3.4%) refused ongoing PMTCT services. Of the 1318 live births to date, 1264 (95.9%) of the mothers and 1285 (97.5%) of the infants received ARV prophylaxis; 1064 (80.7%) infants were tested for HIV by PCR and started on cotrimoxazole. Median age at PCR was 1.7 months (IQR, 1.5 to 2.5). Overall transmission at first PCR was 43/1047 (4.1%). Of the 43 infants with positive PCR results, 36 (83.7%) were enrolled in ART clinic and 33 (76.7%) were initiated on ART. CONCLUSIONS: Case management and support by dedicated CHWs can create a continuum of longitudinal care in the PMTCT cascade and result in improved outcomes.

Prompt initiation of ART With therapeutic food is associated with improved outcomes in HIV-infected Malawian children with malnutrition.

This retrospective observational study of 140 HIV-infected children with uncomplicated malnutrition in urban Malawi tested the hypothesis that initiation of antiretroviral therapy (ART) within 21 days of outpatient therapeutic feeding (prompt ART) improved clinical outcomes. Children receiving prompt ART were more likely to recover nutritionally (86% vs. 60%, P < 0.01) and had higher rates of weight gain (3.6 vs. 1.6 g/k/day; P = 0.02). Logistic regression modeling found prompt ART was associated with increased likelihood of nutritional recovery (odds ratio: 5.4, 95% confidence interval: 2.0 to 14.5). This suggests that prompt ART is associated with improved outcomes in HIV-infected Malawian children with uncomplicated malnutrition.

Pneumonia and malnutrition are highly predictive of mortality among African children hospitalized with human immunodeficiency virus infection or exposure in the era of antiretroviral therapy.

OBJECTIVE: To identify clinical characteristics predicting death among inpatients who are infected with or exposed to human immunodeficiency virus (HIV) during a period of pediatric antiretroviral therapy scale-up in sub-Saharan Africa. STUDY DESIGN: Retrospective review of medical records from every child with HIV infection (n = 834) or exposure (n = 351) identified by routine inpatient testing in Kamuzu Central Hospital, Lilongwe, Malawi, September 2007 through December 2008. RESULTS: The inpatient mortality rate was high among children with HIV infection (16.6%) and exposure (13.4%). Clinically diagnosed Pneumocystis pneumonia or very severe pneumonia independently predicted death in inpatients with HIV infection (OR 14; 95% CI 8.2 to 23) or exposure (OR 21; CI 8.4 to 50). Severe acute malnutrition independently predicted death in children who are HIV infected (OR 2.2; CI 1.7 to 3.9) or exposed (OR 5.1; CI 2.3 to 11). Other independent predictors of death were septicemia, Kaposi sarcoma, meningitis, and esophageal candidiasis for children infected with HIV, and meningitis and severe anemia for inpatients exposed to HIV. CONCLUSIONS: Severe respiratory tract infections and malnutrition are both highly prevalent and strongly associated with death among hospitalized children who are HIV infected or exposed. Novel programmatic and therapeutic strategies are urgently needed to reduce the high mortality rate among inpatients with HIV infection and HIV exposure in African pediatric hospitals.

Routine inpatient human immunodeficiency virus testing system increases access to pediatric human immunodeficiency virus care in sub-Saharan Africa.

BACKGROUND: Routine Human Immunodeficiency Virus (HIV) testing, called provider-initiated opt-out HIV testing and counseling (PITC), is recommended in African countries with high HIV prevalence. However, it is unknown whether PITC increases access to pediatric HIV care. In 2008, the Baylor International Pediatric AIDS Initiative implemented PITC (BIPAI-PITC) at a Malawian hospital. We sought to evaluate the influence of BIPAI-PITC, compared with nonroutine HIV testing (NRT), on pediatric HIV care access. METHODS: Retrospective data from 7077 pediatric inpatients were collected during sequential 4-month periods of NRT and BIPAI-PITC. In-hospital and 1-year outcomes for 337 HIV-infected and HIV-exposed uninfected inpatients not previously enrolled in HIV care were analyzed to assess the clinical influence of each testing strategy. RESULTS: During BIPAI-PITC, a greater proportion of all hospitalized children received HIV testing (81.0% vs. 33.3%, P < 0.001), accessed inpatient HIV-trained care (7.5% vs. 2.4%, P < 0.001), enrolled into an outpatient HIV clinic after discharge (3.2% vs. 1.3%, P < 0.001), and initiated antiretroviral therapy (ART) after hospitalization (1.1% vs. 0.6%, P = 0.010) compared with NRT. Additionally, BIPAI-PITC increased the proportion of hospitalized HIV-infected and HIV-exposed uninfected children receiving DNA polymerase chain reaction testing (73.5% vs. 35.2%, P < 0.001), but did not improve outpatient enrollment or ART initiation of identified HIV-infected patients. CONCLUSIONS: BIPAI-PITC increases access to inpatient and outpatient pediatric HIV care for hospitalized children, including DNA polymerase chain reaction testing and ART. Broader implementation of BIPAI-PITC or similar approaches, along with more pediatric HIV-trained clinicians and improved defaulter-tracking methods, would improve pediatric HIV service utilization globally.

Inadequate coordination of maternal and infant HIV services detrimentally affects early infant diagnosis outcomes in Lilongwe, Malawi.

OBJECTIVE: To assess the continuity of care and outcome of pediatric HIV prevention, testing, and treatment services, focusing on early infant diagnosis with DNA polymerase chain reaction (PCR). DESIGN: A retrospective observational cohort. METHODS: Maternal HIV antibody, infant HIV DNA PCR test results, and outcome data from HIV-infected infants from the prevention of mother-to-child transmission, early infant diagnosis, and pediatric HIV treatment programs operating in Lilongwe, Malawi, between 2004 and 2008 were collected, merged, and analyzed. RESULTS: Of the 14,669 pregnant women who tested HIV antibody positive, 7875 infants (53.7%) received HIV DNA PCR testing. One thousand eighty-four infants (13.8%) were HIV infected. Three hundred twenty (29.5%) children enrolled into pediatric HIV care, with 202 (63.1%) at the Baylor Center of Excellence. Among these, antiretroviral therapy was initiated on 110 infants (54.5%) whose median age was 9.1 months (interquartile range, 5.4-13.8) and a median of 2.5 months (interquartile range, 1.4-5.2) after HIV clinic registration. Sixty-nine HIV-infected infants (34.2%) died or were lost by December 2008. Initiation of antiretroviral therapy increased the likelihood of survival 7-fold (odds ratio, 7.1; 95% confidence interval, 3.68 to 13.70). CONCLUSIONS: Separate programs for maternal and infant HIV prevention and care services demonstrated high attrition rates of HIV-exposed and HIV-infected infants, elevated levels of mother-to-child transmission, late infant diagnosis, delayed pediatric antiretroviral therapy initiation, and high HIV-infected infant mortality. Antiretroviral therapy increased HIV-infected infant survival, emphasizing the urgent need for improved service coordination and strategies that increase access to infant HIV diagnosis, improve patient retention, and reduce antiretroviral therapy initiation delays.

Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children.

The standard first-line antiretroviral (ART) regimen in Malawi for both adults and children is a fixed-dose combination tablet containing stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). This regimen has been shown to yield satisfactory virologic and immunologic outcomes in children. Published studies have described insights into discontinuation of first-line regimen and toxicities of ART in adults, but similar studies in paediatric populations are lacking. A retrospective cohort study was undertaken to assess reasons for discontinuation of the standard first-line ART regimen (d4T/3TC/NVP) in a paediatric population. In total, 1434 patients met eligibility criteria and were included. The cohort had mean and median age at ART initiation of 4.7 years and 2.9 years, respectively (range: 0.1 months-18.7 years). The gender distribution was 47% female and 53% male. Median follow-up time on ART was 1.8 years (range: 2 weeks-3.9 years). A majority (96.2%) of patients were on the standard first-line ART regimen, while 3.8% (54) were on a different regimen. Twenty-eight patients (2.0%) were on an alternative first-line regimen due to toxicities, 22 patients (1.5%) were on a second-line regimen due to ART failure, and four patients (0.3%) were on a non-standard regimen for other clinical reasons. Of the 28 patients who experienced toxicities requiring ART regimen change, 60.7% (17) were caused by NVP, 39.3% (11) by d4T, and none by 3TC. The median time from first-line ART initiation to alternative first-line ART was two months (range: 10 days-28.1 months); 60.7% of patients on alternative first-line ART were male. Average time on ART until switch to second-line ART regimen was 16.3 months (SD: 9.3 months). The probability of failure after one year on first-line regimen was 1.6% (95% CI: 0.9-2.6). There was no compelling evidence in this cohort, representing approximately 10% of all children on ART in Malawi, to support changing the standard paediatric first-line regimen based on early toxicities or failure. However, experience from the national adult cohort, longer term follow up of the paediatric cohort in this study, emerging data on resistance after single-dose NVP containing mother to child transmission antiretroviral prophylaxis, and new 2009 World Health Organization ART recommendations may influence national policy change to a different first-line regimen.

Task shifting routine inpatient pediatric HIV testing improves program outcomes in urban Malawi: a retrospective observational study.

BACKGROUND: This study evaluated two models of routine HIV testing of hospitalized children in a high HIV-prevalence resource-constrained African setting. Both models incorporated "task shifting," or the allocation of tasks to the least-costly, capable health worker. METHODS AND FINDINGS: Two models were piloted for three months each within the pediatric department of a referral hospital in Lilongwe, Malawi between January 1 and June 30, 2008. Model 1 utilized lay counselors for HIV testing instead of nurses and clinicians. Model 2 further shifted program flow and advocacy responsibilities from counselors to volunteer parents of HIV-infected children, called "patient escorts." A retrospective review of data from 6318 hospitalized children offered HIV testing between January-December 2008 was conducted. The pilot quarters of Model 1 and Model 2 were compared, with Model 2 selected to continue after the pilot period. There was a 2-fold increase in patients offered HIV testing with Model 2 compared with Model 1 (43.1% vs 19.9%, p<0.001). Furthermore, patients in Model 2 were younger (17.3 vs 26.7 months, p<0.001) and tested sooner after admission (1.77 vs 2.44 days, p<0.001). There were no differences in test acceptance or enrollment rates into HIV care, and the program trends continued 6 months after the pilot period. Overall, 10244 HIV antibody tests (4779 maternal; 5465 child) and 453 DNA-PCR tests were completed, with 97.8% accepting testing. 19.6% of all mothers (n = 1112) and 8.5% of all children (n = 525) were HIV-infected. Furthermore, 6.5% of children were HIV-exposed (n = 405). Cumulatively, 72.9% (n = 678) of eligible children were evaluated in the hospital by a HIV-trained clinician, and 68.3% (n = 387) successfully enrolled into outpatient HIV care. CONCLUSIONS/SIGNIFICANCE: The strategy presented here, task shifting from lay counselors alone to lay counselors and patient escorts, greatly improved program outcomes while only marginally increasing operational costs. The wider implementation of this strategy could accelerate pediatric HIV care access in high-prevalence settings.

Early clinical outcomes in children enrolled in human immunodeficiency virus infection care and treatment in lesotho.

BACKGROUND: Children are largely underrepresented among those accessing treatment of HIV infection in Africa. Reported outcomes of children enrolled in national care and treatment programs are needed to inform the widespread scale-up of pediatric HIV care in resource-limited settings. METHODS: The objective of this article is to report on the early outcomes of a pediatric HIV infection care and treatment program in Lesotho during its first 14 months of operation. Clinical protocols are described, and characteristics and outcomes of the first cohort of children enrolled in care are reported, derived from a retrospective review of medical records. RESULTS: In the program's first 14 months, 1566 children and adolescents aged between 0 and 16 years were evaluated for HIV, with 567 (36%) confirmed to be infected. Of infected patients, 61% presented with advanced or severe symptoms of HIV disease and 65% presented with CD4 profiles consistent with advanced or severe immunodeficiency, based on World Health Organization 2006 guidelines. Two hundred and eighty four children received highly active antiretroviral therapy. The mortality rate was 18.6 deaths per 100 patient years of follow-up. Ninety-nine percent of deaths occurred within 90 days of enrollment. Deceased patients were significantly younger, had higher rates of stunting and wasting, and were more likely to present with low CD4 cell counts. CONCLUSION: Highly active antiretroviral therapy was well tolerated, but the early mortality rate was high despite concurrent management of HIV and comorbidities. Given that hundreds of thousands of children remain without access to HIV care, renewed efforts are needed to reach this underserved population.