Laboratory Diagnosis of Sexually Transmitted Infections in Cases of Suspected Child Sexual Abuse.

Laboratory diagnosis of microbial agents associated with sexually transmitted infections plays an important role in both the care of victims of child sexual abuse (CSA) and the investigation of suspected CSA incidents, with law enforcement implications. Rapid and sensitive test results prompt immediate actions to treat and protect the victimized children. The development and maturation of automated nucleic acid amplification tests (NAATs) has greatly improved the assay sensitivity and specificity, with only a 1- to 2-h turnaround time. Unfortunately, the performance characteristics of NAATs have been determined largely with a few limited specimen types and evaluated in adults only. This minireview attempts to cover the scope of infectious agents potentially implicated in CSA, specimen collection, laboratory test modalities, and laboratory report constraints, further complicated by infrequently collected specimen types from prepubertal children <13 years of age.

Plasma and cerebrospinal fluid herpes simplex virus levels at diagnosis and outcome of neonatal infection.

OBJECTIVE: To evaluate the utility of quantitative herpes simplex virus (HSV) polymerase chain reaction (PCR) levels for prognosis and management of neonatal HSV disease. STUDY DESIGN: Clinical and virologic data were abstracted by medical record review from neonatal HSV cases treated at Seattle Children's Hospital between 1993 and 2012. HSV PCR results from plasma (n = 47), cerebrospinal fluid (n = 56), or both (n = 40) at the time of diagnosis were available from 63 infants; 26 with skin-eye-mouth (SEM), 18 with central nervous system (CNS), and 19 with disseminated (DIS) disease. RESULTS: Plasma HSV PCR was positive in 78% of the infants with SEM, 64% with CNS and 100% with DIS disease. Mean plasma viral level was 2.8 log10 copies/mL in SEM, 2.2 log10 copies/mL in CNS, and 7.2 log10 copies/mL in DIS infants. The HSV levels were higher among infants who died compared with surviving infants, 8.1 log10 copies/mL (range 7.7-8.6) vs 3.8 log10 copies/mL (range 0.0-8.6), P = .001, however, level of HSV DNA in the cerebrospinal fluid or in plasma did not correlate with neurologic outcome. Dynamics of HSV clearance from plasma during high-dose acyclovir treatment showed single-phase exponential decay with a median viral half-life of 1.26 days (range: 0.8-1.51). CONCLUSIONS: Plasma HSV levels correlate with clinical presentation of neonatal HSV disease and mortality, but not neurologic outcome.

A Cross-Sectional Survey of Pediatric Infectious Disease Physicians' Approach to Congenital Cytomegalovirus Infection.

Congenital cytomegalovirus (cCMV) continues to be a major public health care issue due to its high prevalence throughout the world. However, there is a paucity of studies evaluating how providers manage this infection. This study surveyed North American Pediatric Infectious Disease (PID) physicians to elicit their approach towards the evaluation and treatment of this condition. Thirty-two PID physicians responded to this survey. Institutional testing and screening for cCMV were infrequently reported. The respondents in general agreed upon most laboratory and diagnostic testing except for neuroimaging. For those tests, there was a disparity in indications for head ultrasound versus brain MRI imaging. Most (68.8%) agreed with the clinical practice of starting valganciclovir in an infant less than 1 month of age with one sign or symptom of disease, and 62.5% would do so for an infant with isolated sensorineural hearing loss. However, only 28.1% would treat cCMV-infected infants older than 1 month of age. In conclusion, few healthcare institutions represented by PID physicians in this cohort had a cCMV screening or testing initiative, yet most respondents would test at a much higher level based on their clinical practice. While there is general consensus in evaluation and treatment of these children, there are disparities in practices regarding neuroimaging and indications for antiviral treatment with respect to age and severity of disease. There is a great need for an evidence based policy statement to standardize cCMV workup and treatment.

A novel formulation enabled transformation of 3-HIV drugs tenofovir-lamivudine-dolutegravir from short-acting to long-acting all-in-one injectable.

OBJECTIVE: To develop an injectable dosage form of the daily oral HIV drugs, tenofovir (T), lamivudine (L), and dolutegravir (D), creating a single, complete, all-in-one TLD 3-drug-combination that demonstrates long-acting pharmacokinetics. DESIGN: Using drug-combination-nanoparticle (DcNP) technology to stabilize multiple HIV drugs, the 3-HIV drugs TLD, with disparate physical-chemical properties, are stabilized and assembled with lipid-excipients to form TLD-in-DcNP . TLD-in-DcNP is verified to be stable and suitable for subcutaneous administration. To characterize the plasma time-courses and PBMC concentrations for all 3 drugs, single subcutaneous injections of TLD-in-DcNP were given to nonhuman primates (NHP, M. nemestrina ). RESULTS: Following single-dose TLD-in-DcNP , all drugs exhibited long-acting profiles in NHP plasma with levels that persisted for 4 weeks above predicted viral-effective concentrations for TLD in combination. Times-to-peak were within 24 hr in all NHP for all drugs. Compared to a free-soluble TLD, TLD-in-DcNP provided exposure enhancement and extended duration 7.0-, 2.1-, and 20-fold as AUC boost and 10-, 8.3-, and 5.9-fold as half-life extension. Additionally, DcNP may provide more drug exposure in cells than plasma with PBMC-to-plasma drug ratios exceeding one, suggesting cell-targeted drug-combination delivery. CONCLUSIONS: This study confirms that TLD with disparate properties can be made stable by DcNP to enable TLD concentrations of 4 weeks in NHP. Study results highlighted the potential of TLD-in-DcNP as a convenient all-in-one, complete HIV long-acting product for clinical development.

Pharmacokinetics, Tolerability, and Safety of Doravirine and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Week 24 Results From IMPAACT 2014.

BACKGROUND: We studied the pharmacokinetics (PK) and safety of 100-mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed-dose combination (100/300/300 mg DOR FDC) treatment in adolescents with HIV-1. METHODS: Adolescents ages 12 to younger than 18 years were enrolled in 2 sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100-mg single-dose doravirine in adolescents ≥35 kg. Cohort 2 participants either initiated treatment with DOR FDC (antiretroviral (ARV)-naïve) or switched to DOR FDC from a previous ARV regimen (virologically suppressed). The first 10 Cohort 2 participants had intensive PK evaluations, and safety, sparse PK, and HIV RNA were assessed through week 24. RESULTS: Fifty-five adolescents, median age 15.0 years and baseline weight 51.5 kg, were enrolled. Nine participants completed Cohort 1 PK assessments (8 of the 9 participants weighed ≥45 kg) and 45 initiated study drug in Cohort 2. The doravirine geometric mean (GM) AUC 0-∞ was 34.8 µM∙hour, and the GM C 24 was 514 nM after a single dose, with a predicted steady-state GM C 24,ss,pred of 690 nM. Cohort 2 enrolled adolescents weighing ≥45 kg. Plasma concentrations of doravirine, tenofovir, and lamivudine achieved by Cohort 2 participants were similar to those reported in adults. No drug-related serious or grade 3 or 4 adverse events occurred. Forty-two of 45 participants (93.3%; 95% CI: [81.7, 98.6]) achieved or maintained HIV-1 RNA <40 copies/mL. CONCLUSIONS: Doravirine and DOR FDC achieved target PK in adolescents with HIV-1. DOR FDC was well-tolerated and maintained excellent virologic efficacy through 24 weeks, offering a favorable option for adolescents.

Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014.

BACKGROUND: IMPAACT 2014 study is a phase I/II, multicenter, open-label, nonrandomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed-dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks. METHODS: Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at weeks 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events (AEs) and treatment discontinuations. RESULTS: A total of 45 adolescents, median age 15 (range, 12-17) years, 58% females, were enrolled and 2 (4.4%) participants were ARV naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed the study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4-99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6-98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to AEs and no drug-related AEs ≥grade 3 or deaths. CONCLUSIONS: We found once-daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.

Neonatal Herpes Simplex Virus Infection: Epidemiology and Outcomes in the Modern Era.

BACKGROUND: Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV. METHODS: Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016. RESULTS: One hundred thirty infants with a diagnosis of neonatal HSV were identified. Between 1980 and 2016, high-dose acyclovir treatment for neonatal HSV infection increased from 0% to close to 95%, with subsequent decrease in overall HSV-related mortality from 20.9% to 5.6%. However, even among infants treated with high-dose acyclovir, mortality was 40.9% for infants with disseminated (DIS) disease, and only 55% of infants with central nervous system (CNS) disease were without obvious neurologic abnormalities at 24 months. Over the study period, the time between initial symptoms and diagnosis decreased. Skin recurrences were more common with HSV-2 than HSV-1 (80% vs 55%; P = .02) and in infants with lesions at initial diagnosis (76% vs 47%; P = .02). CONCLUSION: Changes in the standard of care for management of neonatal HSV disease have led to improvements in timeliness of diagnosis and outcome but mortality in infants with DIS disease and neurologic morbidity in infants with CNS disease remain high. Future research should focus on prevention of perinatal infection and subsequent recurrences.

HIV Transmission Through Premastication.

Premastication is a potential route of transmission of HIV from caregiver to child. We report the case of a 13-month-old Alaska Native child from rural Alaska who presented with failure to thrive, recurrent pneumonias, severe dental decay, and dysphagia. The mother was HIV-uninfected. Respiratory failure prompted transfer to a children's hospital outside of Alaska where the child received a diagnosis of HIV infection. A grandparent who had been acting as primary caregiver was discovered to be HIV-infected with detectable viral load resulting from intermittent nonadherence to her medication regimen. This grandparent reported feeding the child premasticated food. Sequencing of the hypervariable C2V5 region of the HIV envelope gene in both patients demonstrated less than 0.05% variation, consistent with transmission from grandparent to child. Health care providers should be aware that transmission of HIV can occur via premastication, educate parents and caregivers regarding this risk, and rigorously pursue HIV testing when indicated even in children with HIV-uninfected mothers.

Via media: Role and responsibilities of the independent safety officer.

Every research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk. ISOs are clinicians or researchers with relevant expertise who are independent of the investigator and the research study. Their relationship to the study is defined by a formal charter which is aligned with the protocol and Data and Safety Monitoring Plan to address the oversight process, responsibilities of the ISO, and clearly describe the variables to be monitored. The ISO responsibilities include reviewing safety data, adverse events, recruitment, demographics, study progress, data quality, protocol changes, and any new scientific information that pertains to the trial. Finally, the ISO reports in their review on any significant findings may propose modifications to the study or a need to stop the trial.

Cord blood lipids in infants born to HIV-1-infected women treated with combination antiretroviral therapy.

BACKGROUND: To investigate the effect of exposure to protease inhibitor (PI) therapy in utero on cord blood lipids in infants born to mothers enrolled in AIDS Clinical Trials Group protocol 5084, a prospective, multicentre, observational study of antiretroviral therapy (ART) during pregnancy. METHODS: Clinical outcome was determined in 80 infants born to women treated with PIs and 73 infants born to women treated with other antiretrovirals during pregnancy. Cord blood serum from 117 of these infants was assayed for total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein A1 (apoA1), apolipoprotein B100 (apoB) and lipoprotein (a). Covariates considered in the analysis included race/ethnicity, gestational age, infant gender, infant birth weight, mode of delivery, maternal tobacco and alcohol use, post-partum body mass index, and ART duration. RESULTS: Cord blood total and HDL cholesterol, triglyceride, apoA1, apoB, lipoprotein (a) and apoB/apoA1 ratio were not different between the two groups. Cord blood lipid levels in these HIV-exposed infants were similar to those reported in other neonatal cohorts. Controlling for race/ethnicity, infants born to women treated with PIs had higher LDL cholesterol than those born to women not treated with PIs (29 mg/dl versus 27 mg/dl, P = 0.006). CONCLUSION: Only LDL cholesterol was significantly higher in the cord blood of PI-exposed infants versus those not exposed to PIs in utero. As the difference between the two groups was small, the clinical relevance of the effect of maternal PI treatment on infant LDL cholesterol levels at birth is not clear.

Effectiveness of antenatal group HIV voluntary counseling and testing services in rural India.

This study assessed HIV attitudes among pregnant women attending antenatal clinics in the Namakkal district of Tamilnadu, India, as well as HIV knowledge before and after group counseling sessions. Two hundred thirteen women (97%) attending five antenatal clinics in July 2004 accepted HIV counseling and testing and completed precounseling and postcounseling questionnaires. Although the majority of women had heard of HIV, precounseling knowledge was low (mean precounseling score; 6.9/18, SD: 4.53), with scores correlating with the women's educational level and the number of sources from which they had received information about HIV. Posttest scores increased by 21%, however, understanding of modalities to prevent HIV infection remained poor. Group counseling sessions achieve small gains in HIV knowledge, but there is a continued need for ongoing and multifaceted HIV education in rural India.

Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-Infected Children on Long-term Suppressive Antiretroviral Therapy.

BACKGROUND: Data on long-term toxicity of antiretroviral therapy (ART) in HIV-infected children are sparse. PENPACT-1 was an open-label trial in which HIV-infected children were assigned randomly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. METHODS: We examined changes in clinical, immunologic, and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART. Liver enzyme, creatinine, and cholesterol levels and hematologic parameters were assessed during the trial. Cystatin C, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) were assayed from cryopreserved specimens. RESULTS: Ninety-nine children (52 on PI-based and 47 on NNRTI-based ART) met inclusion criteria. The median age at initiation of ART was 6.5 years (interquartile range [IQR], 3.7-13.4 years), and 22% were aged <3 years at ART initiation; 56% of the PI-treated children received lopinavir/ritonavir, and 70% of NNRTI-treated children received efavirenz initially. We found no evidence of significant clinical toxicity in either group; growth, liver, kidney, and hematologic parameters either remained unchanged or improved between baseline and year 4. Total cholesterol levels increased modestly, but no difference between the groups was found. IL-6 and hs-CRP levels decreased more after 4 years in the NNRTI-based ART group. The median change in IL-6 level was -0.35 pg/ml in the PI-based ART group and -1.0 in the NNRTI-based ART group (P = .05), and the median change in hs-CRP level was 0.25 µg/ml in the PI-based ART group and -0.95 µg/ml in the NNRTI-based ART group (P = .005). CONCLUSION: These results support the safety of prolonged ART use in HIV-infected children and suggest that suppressive NNRTI-based regimens can be associated with lower levels of systemic inflammation.

Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial.

INTRODUCTION: Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a "bridging strategy" to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. MATERIALS & METHODS: Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. RESULTS: Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14-20), 472 cells/mm3 (IQR 384-651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2-4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. CONCLUSIONS: Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed. TRIAL REGISTRATION: Clinical Trials.gov NCT01338025.

Safety and Efficacy of Atorvastatin in Human Immunodeficiency Virus-infected Children, Adolescents and Young Adults With Hyperlipidemia.

BACKGROUND: Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population. METHODS: HIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy. RESULTS: Twenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin. CONCLUSIONS: Atorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children.

Rapid HIV type 1 testing of women presenting in late pregnancy with unknown HIV status in Lima, Peru.

We studied the feasibility and acceptability of HIV-1 testing using rapid serological assays in pregnant women presenting in late pregnancy without prior HIV-1 testing. Pregnant women presenting to the emergency room at the Instituto Materno-Perinatal in Lima, Peru, were offered on-site rapid HIV-1 testing. Consenting women were provided HIV counseling and had samples taken for rapid detection of antibodies in the blood and oral secretions. Women testing HIV-1 seropositive by one or both assays were offered standard HIV obstetrical care including antiretrovirals. Between October 2000 and August 2001, 3543 women were tested for HIV-1 antibodies through the rapid testing protocol. Twenty-seven women tested positive by one or both assays. Standard EIA results were negative for two of the 27 women and EIA results were not available for an additional three women. Seventeen of the 19 women (89%) for whom delivery information is available received antiretroviral therapy prior to delivery. Eighty percent of the women treated with nevirapine received the drug at least 1 hr prior to delivery. Study personnel reported problems with performing the rapid assays for less than 1% of the samples and the majority of the women did not express a preference for either the oral fluid or blood sample collection. While HIV-1 testing early in pregnancy is preferable, rapid HIV-1 testing in late pregnancy or at delivery is feasible, acceptable to most women, and allows for timely intervention to reduce maternal-child transmission.

Efficacy and toxicity of antiretroviral therapy using 4 or more agents: application of a strategy for antiretroviral management in human immunodeficiency virus-infected children.

OBJECTIVE: To characterize the long-term tolerance and virologic efficacy of combination antiretroviral therapy consisting of 4 or more agents in a clinical setting. METHODS: An observational review of 36 children infected with human immunodeficiency virus 1 (HIV-1) treated with 4 or 5 antiretroviral agents in 2 university hospital clinics between April 1, 1996, and October 31, 2000. Highly active antiretroviral therapy regimens were chosen with regard to the child's past antiretroviral exposure or results of genotypic resistance data. Plasma HIV-1 RNA levels were monitored weekly to monthly after initiation of highly active antiretroviral therapy, and adherence efforts were actively supported and monitored. MAIN OUTCOME MEASURE: Number of children with undetectable plasma HIV-1 RNA levels at longest follow-up. RESULTS: Four- or 5-drug highly active antiretroviral therapy reduced plasma HIV-1 RNA levels to less than 50 copies/mL in 32 (89%) of 36 children. After a median of 28.7 months of observation, 28 children (78%) remained at this level of suppression. Adverse reactions were limited to mild neutropenia and mild transient or persistent elevations in alanine aminotransferase levels in 11% of children. CONCLUSIONS: Treatment with 4 or 5 antiretroviral agents was well tolerated in HIV-1-infected children and resulted in a high degree of viral suppression, even in children with previous antiretroviral drug experience.

Using CD4 percentage and age to optimize pediatric antiretroviral therapy initiation.

BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization "mild" immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with "severe" immunosuppression, more children with "mild" immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or "advanced" immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with "mild" immunosuppression at any age or "advanced" immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks.

HIV/HBV coinfection in children and antiviral therapy.

Small cohort studies from countries where both HIV and HBV are endemic demonstrate prevalence rates of chronic hepatitis B in HIV-infected children of between 1 and 49%. While data on coinfected children are limited, results from studies in adults with HIV/HBV coinfection raise the concern that coinfected children may be at a higher risk of liver disease, hepatic fibrosis and cirrhosis. With the scale-up of combination antiretroviral therapy worldwide, of which lamivudine is included in most first-line regimens, coinfected children treated with lamivudine risk development of HBV resistance mutations. This article summarizes the current literature relevant to HIV/HBV coinfection in children, the options for treatment and highlights priorities for future research.