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.

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.

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.

A simplified weight-based method for pediatric drug dosing for zidovudine and didanosine in resource-limited settings.

BACKGROUND: Zidovudine and didanosine are antiretroviral drugs used for human immunodeficiency virus (HIV)-infected children with dose recommendations based on body surface area calculations. Although weight and height can both be measured, it may be impractical to expect providers in resource-limited settings to estimate accurately body surface area. METHODS: We developed an antiretroviral dosing chart based on authoritative sources for brand name drugs in weight bands (ie, 5-6.9, 7-9.9, 10-11.9, 12-14.9, 15-16.9, 17-19.9, 20-24.9, 25-29.9, 30-34.9 and 35-40 kg) to assist proper dosing of antiretrovirals for HIV-infected children in resource-limited settings. For drugs dosed by body surface area, we estimated likely weights and heights for age using standardized US growth charts for girls from which doses in weight bands were calculated. For this analysis, we calculated the difference between weight-based doses and body surface area-based doses for zidovudine 10 mg/mL oral solution, zidovudine 100-mg capsules, and didanosine 25, 50 and 100-mg chewable tablets using actual heights and weights from HIV-infected children in Africa and Romania. RESULTS: We used 1752 observations from 826 HIV-infected children (48% girls) from 9 countries. A total of 454 observations were in children <20 kg and 1298 > or =20 kg. For those <20 kg, the median difference of the weight-based dose as compared with the body surface area-based dose for zidovudine solution was -6.4% (range, -22.6, +13.7), zidovudine capsules +3.1% (range, -38.8, +44.7), didanosine chewable tablets +0.7% (range, -24.4, +22.5); for those > or =20 kg for zidovudine solution was 0.0% (range, -16.4, +11.8), zidovudine capsules +7.6% (range, -16.4, +36.9) and didanosine chewable tablets +1.2% (range, -16.4, +14.1). The dose precision for children <20 versus > or =20 kg was different for zidovudine solution (P < 0.001) and zidovudine capsules (P < 0.001), but not didanosine chewable tablets. The frequency that weight-based dose was more than 20% less than the body surface area-based dose for those <20 kg was 1.3% for zidovudine solution, 27.2% for zidovudine capsules and 4.9% for didanosine chewable tablets. For those > or =20 kg, the weight-based dose was never more than 20% less than the body surface area-based dose. CONCLUSION: Dosing zidovudine and didanosine by weight band provides reasonably precise dosing as compared with body surface area-based doses. However, use of zidovudine capsules in children <20 kg results in under dosing by >20% in many instances. Didanosine chewable tablets allow for higher dosing precision compared with zidovudine capsules because of increased flexibility in the dosage form. Solid dosage forms of antiretroviral medications designed specifically for children are urgently needed.

Comparison of atovaquone and azithromycin with trimethoprim-sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin. METHODS: A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years. RESULTS: Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles. CONCLUSIONS: We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.

Longitudinal study of the prevalence and prognostic implications of oral manifestations in romanian children infected with human immunodeficiency virus type 1.

OBJECTIVE: We evaluated the prevalence and predictive value for human immunodeficiency virus (HIV) disease progression of oral manifestations in Romanian children. METHODS: A nonrandom sample of 238 HIV-infected children was followed prospectively between 1998 and 2001 at the Romanian-American Children's Center in Constanta, Romania. Study subjects underwent comprehensive annual oral examinations. Oral manifestations of interest, demographic data and other selected medical information were recorded at baseline and at each subsequent visit. Descriptive statistics and survival analysis methods were used in the study. A level of statistical significance of alpha = 0.05 was used. RESULTS: The study subjects' mean age was 9.9 +/- 1.2 (SD) years. The most common oral lesions were gingivitis (49%), parotid enlargement (13%) and oral candidiasis (11%). Oral candidiasis was associated with progression to acquired immunodeficiency syndrome or death (whichever occurred first) (log rank P = 0.03) and with death (log rank P < 0.001). Oral hairy leukoplakia also was associated with progression to death (log rank P = 0.001). The risk of dying was 3.43 (95% confidence interval, 1.86-6.34; P < 0.001) for children who had oral candidiasis at baseline and 4.62 (95% confidence interval, 1.67-12.77; P = 0.003) for those who had oral hairy leukoplakia. CONCLUSIONS: Oral manifestations occur commonly among HIV-infected Romanian children. Oral candidiasis and oral hairy leukoplakia were positive predictors of HIV disease progression.

Treatment of human immunodeficiency virus (HIV) in children using antiretroviral drugs.

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is having a devastating impact on African men, women and children. Antiretroviral treatment of children has lagged behind that of adults in Africa and globally. Fortunately, several national and international initiatives are helping to catalyze access of HIV-infected children to treatment. In general, the principles of antiretroviral treatment are the same for resource-rich and resource-poor settings. However, the more rapid progression of HIV disease often observed among children in Africa and some other resource-poor settings may argue for a more aggressive approach to initiation of treatment. In addition, numerous barriers to treatment of HIV-infected children in Africa and other resource-poor settings exist and must be overcome, including the expense of antiretroviral medications, lack of pediatric drug formulations, and poor human capacity and infrastructure for treatment administration. The 2.2 million African children currently living with HIV/AIDS, and many more living in poor countries on other continents, are dependent on all of us to work creatively to overcome barriers to the large-scale implementation of programs for health-restoring, life-prolonging antiretroviral treatment.

High prevalence of hepatitis B virus markers in Romanian adolescents with human immunodeficiency virus infection.

BACKGROUND: We evaluated the frequency of hepatitis coinfection in Romanian adolescents who were diagnosed with human immunodeficiency virus (HIV) infection prior to 1995. METHODS: One hundred sixty-one adolescents (13-18 years of age) with symptomatic HIV infection, but without signs of hepatic dysfunction, and 356 age-matched, HIV-uninfected controls underwent laboratory testing for markers of parenterally acquired hepatitis virus infection. RESULTS: Seventy-eight percent of HIV-infected adolescents had markers of past or present hepatitis B virus (HBV) infection, as compared with 32% of controls ( P = .0001). The prevalence of HBV replicative markers was more than 5-fold higher in HIV-infected adolescents as compared with controls: 43.4% vs 7.9% ( P = .0001), respectively, for hepatitis B surface antigen (HBsAg); and 11.2% vs 2.2% ( P = .0001), respectively, for hepatitis B e antigen (HBeAg). The prevalence of HBsAg chronic carriers and the presence of HBV replicative markers was significantly higher in patients with immunologically defined AIDS (CD4+ cell counts < 200 cells/mcL): 59.6% vs 34.6% ( P = .02) for HBsAg and 22.8% vs 5.7 %, ( P = .002) for HBV DNA. After 1 year of follow-up, the proportion of those who cleared the HBeAg was considerably lower in severely immunosuppressed coinfected patients: 4.7% vs 37.1% ( P = .003). Four additional HIV-infected adolescents became HBsAg-positive over the term of follow-up (incidence rate, 24.9/1000 person-years), despite a record of immunization against hepatitis B. CONCLUSIONS: A substantial percentage of HIV-infected and HIV-uninfected Romanian adolescents have evidence of past or present HBV infection. In HIV-infected adolescents, the degree of immunosuppression is correlated with persistence of HBV replicative markers, even in the absence of clinical or biochemical signs of liver disease.

Pharmacokinetics and pharmacodynamics of saquinavir in pediatric patients with human immunodeficiency virus infection.

OBJECTIVE: Our objective was to investigate the clinical pharmacologic characteristics of saquinavir given as a soft gelatin capsule, either alone or in combination with nelfinavir, to children and adolescents with human immunodeficiency virus infection. METHODS: The pharmacokinetics of 50 mg/kg saquinavir 3 times a day (tid) alone versus 33 mg/kg saquinavir tid plus 30 mg/kg nelfinavir tid was assessed after single-dose administration and after short- and long-term administration. The single-dose pharmacokinetics of fixed (1200 mg) versus unrestricted weight-adjusted dosing (50 mg/kg) was also investigated. RESULTS: Saquinavir as the sole protease inhibitor resulted in lower saquinavir exposure in children (steady-state geometric mean area under the concentration-time curve from time zero to 24 hours [AUC (0-24 h)], 5790 ng x h/ml; steady-state concentration 8 hours after drug administration [C(8h,SS)], 65 ng/ml) and adolescents [steady-state geometric mean AUC(0-24 h), 5914 ng x h/ml] than that reported in adults treated with 1200 mg tid [steady-state geometric mean AUC(0-24 h), 21,700 ng x h/ml; C(8h,SS), 223 ng/ml]. This finding appeared to be attributable to markedly higher apparent oral clearance, potentially as a result of increased systemic clearance and reduced oral bioavailability. Nelfinavir combined with saquinavir reduced apparent oral clearance, increasing saquinavir exposure in children [steady-state geometric mean AUC(0-24 h), 11,070 ng x h/ml; C(8h,SS), 380 ng/ml] to levels that approach those observed in adults. A significant correlation between average trough concentration and sustained viral load suppression was observed in children. The apparent threshold for maintaining viral load suppression was a mean trough saquinavir concentration above 200 ng/ml. CONCLUSIONS: The pharmacokinetics of saquinavir in children is different from that of adults, and administration of saquinavir alone will not give consistently efficacious plasma levels. The best way of improving saquinavir exposure in children is through combination therapy with other protease inhibitors that inhibit saquinavir metabolism.

False negative DNA polymerase chain reaction in an infant with subtype C human immunodeficiency virus 1 infection.

Diagnosis of HIV infection in early infancy generally relies on detection of HIV proviral DNA by PCR. However, many of the HIV DNA PCR assays currently in use are either not optimized or have not been validated for diagnosis of infection with non-subtype B HIV. We report the case of an HIV-infected African American immigrant infant with subtype C HIV infection who tested negative repeatedly by HIV DNA PCR. Clinicians should be aware of this particular limitation of HIV DNA PCR assays, because it is likely that an increasing proportion of the HIV-infected infants seen in US centers will be infected with non-subtype B HIV.

Lipodystrophy syndrome in human immunodeficiency virus-infected children.

BACKGROUND: Lipodystrophy syndrome in HIV-infected adults is characterized by a variety of physical and/or metabolic abnormalities, including fat redistribution, hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) and peripheral insulin resistance. Many studies suggest that antiretroviral therapy is the underlying cause of the condition. Few data exist for HIV-infected children. METHODS: This is a cross-sectional study evaluating HIV-infected children age 2 to 16 years. Fat redistribution was identified by physical examination and parental questionnaire. Fasting blood analysis included cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, glucose, insulin and C-peptide. RESULTS: Forty HIV-infected children were recruited. Seven children (18%) exhibited physical signs of fat redistribution. Twenty-seven (68%), 11 (28%) and 3 (8%) children exhibited evidence for hypercholesterolemia, hypertriglyceridemia and insulin resistance, respectively. Eleven children (28%) had no physical signs or laboratory evidence of lipodystrophy. Statistical analysis did not reveal any significant association between the presence of lipodystrophic features and patient age, HIV-1 viral load, exposure to specific antiretroviral medications or duration of protease inhibitor or nucleoside reverse transcriptase inhibitor therapy. Drug dosing was significantly associated with the development of lipodystrophy features. Children receiving pediatric dosing regimens vs. adult dosing regimens were less likely to develop lipodystrophy (P = 0.003). CONCLUSIONS: Features associated with lipodystrophy syndrome arise in some HIV-infected children. Subjects receiving pediatric dosing regimens were less likely than those receiving adult regimens to develop lipodystrophy.

Disseminated Acanthamoeba infection in a human immunodeficiency virus-infected infant.

Infection with Acanthamoeba is difficult to diagnose and treat. We present the first case of disseminated Acanthamoeba infection in an HIV-infected infant. The infant survived 2 years with treatment with several agents having anti-Acanthamoeba activity in vitro.

Efavirenz liquid formulation in human immunodeficiency virus-infected children.

BACKGROUND: This study determined the safety, pharmacokinetics, antiviral activity and immunologic effects of efavirenz liquid formulation, nelfinavir and nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-infected children, 3 to 9 years of age. METHODS: Plasma HIV-1 RNA and lymphocyte subsets were measured at various intervals after initiation of therapy. Pharmacokinetic studies were performed at Week 2, and doses of efavirenz and nelfinavir were adjusted if area under the curve values fell outside specified target ranges. RESULTS: This combination of antiretrovirals was well-tolerated. Pharmacokinetic values were similar to those observed in a previous study of older children who received efavirenz capsules in combination with nelfinavir and NRTIs. After 48 weeks of therapy 63% of subjects had plasma HIV RNA levels of <400 copies/ml, and 58% had <50 copies/ml in an intent-to-treat analysis. CD4 cell count and percentage rose significantly over this time, whereas the number of activated CD8 cells declined. CONCLUSIONS: Combination therapy with efavirenz liquid formulation, nelfinavir and NRTIs is an attractive treatment option for HIV-infected children >3 years of age who are unable to take efavirenz capsules.

Comprehensive pediatric human immunodeficiency virus care and treatment in Constanta, Romania: implementation of a program of highly active antiretroviral therapy in a resource-poor setting.

BACKGROUND: Relatively few human immunodeficiency virus (HIV)-infected children worldwide have access to care and treatment. The Romanian-American Children's Center, a collaborative project of a U.S. health care institution and the Romanian government, has established a comprehensive program of highly active antiretroviral therapy for children in Constanta, Romania. OBJECTIVES: To describe the design and outcomes of a program of pediatric HIV/acquired immunodeficiency syndrome (AIDS) care and treatment in a resource-poor setting. SETTING: Outpatient center providing comprehensive primary and HIV/AIDS specialty care and treatment to all known HIV-infected children living in Constanta County, Romania. OUTCOMES: As of August 2003, a total of 452 children were receiving highly active antiretroviral therapy. Therapy has been well-tolerated, with approximately 90% of children continuing to receive treatment after a median duration of follow-up of 67 weeks. Normal weight and height growth velocities have been observed among treated children. Marked decreases have been observed in rates of hospitalization and mortality. The mean change in CD4+ lymphocyte count for 173 children who have both a baseline count and at least 1 follow-up count is +284 cells/microL (P < 0.0001). CONCLUSIONS: Highly active antiretroviral therapy can be administered safely and effectively to children in a resource-poor setting, with outcomes comparable with those observed in U.S. pediatric antiretroviral clinical trials.

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.