Jacobo Abadi

Cryptococcosis in Children with AIDS

We compiled the clinical and immunologic features of Cryptococcus neoformans infections in human immunodeficiency virus (HIV)-infected children from 1985 to 1996 in a retrospective case series. Thirty cases of cryptococcosis were identified. These children had a median age of 9.8 years, a median CD4+ cell count of 54/microL at the time of diagnosis, and either a culture positive for C. neoformans or cryptococcal antigen in serum or cerebrospinal fluid. Sixty-three percent of the cases occurred in children vertically infected with HIV and in children between 6 and 12 years of age. The clinical and laboratory characteristics of this pediatric cohort were similar to those of adults with AIDS and cryptococcosis. On the basis of a subset of the cases, a 10-year point prevalence of cryptococcosis among children with AIDS of approximately 1% was estimated.

Human Antibodies Elicited by a Pneumococcal Vaccine Express Idiotypic Determinants Indicative of Vh3 Gene Segment Usage

Human immunodeficiency virus (HIV)-infected persons manifest decreased antibody responses to pneumococcal polysaccharide vaccines. Since human antibody responses to polysaccharides are often restricted, the molecular structure of antibodies elicited by a 23-valent pneumococcal vaccine was analyzed. Anti-idiotypic reagents were used to detect V(H)1, V(H)3, and V(H)4 gene usage by antibodies to pneumococcal capsular polysaccharides in HIV-uninfected and HIV-infected subjects by ELISA. HIV-uninfected persons generated beta-mercaptoethanol-sensitive and -resistant antibodies to pneumococcal capsular polysaccharides expressing V(H)3 determinants recognized by the D12, 16.84, and B6 monoclonal antibodies; antibodies expressing V(H)1 determinants were not detected, and V(H)4 determinants were expressed by beta-mercaptoethanol-sensitive antibodies only; and HIV-infected subjects had significantly lower capsular polysaccharide-specific and V(H)3-positive antibody responses. These findings confirm decreased antibody responses to pneumococcal vaccination in HIV-infected persons and suggest that their poor responses may result from HIV-associated depletion of restricted B cell subsets.

Prevalence of Hepatitis B and C Virus Infections in Children Infected with HIV

We evaluated the prevalence and transmission mode of hepatitis B and C in an inner-city, pediatric cohort of human immunodeficiency virus (HIV)-infected persons, as well as the demographic characteristics of the cohort. Hepatitis B or C was found in 13 (5.8%) of 228 children. This analysis suggests that chronic hepatitis is prevalent and should be routinely screened for in the pediatric HIV-infected population.

Pregnancy in women with perinatally acquired HIV-infection: outcomes and challenges.

This is a retrospective comparison of pregnant women with perinatally acquired HIV-infection (PAH) with a cohort of pregnant women with behaviorally acquired HIV-infection (BAH). PAH cases (11 women) included all pregnant adolescents followed at our HIV clinic from January 2000 to January 2009. BAH cases (27 women) were randomly selected from all deliveries within the study period at the same institution. Demographics, mode of delivery, CD4+ counts, and viral loads (VLs) before, during, and six months postpartum, as well as neonatal outcomes, were reviewed. CD4 counts were significantly lower in the PAH group. VLs were statistically higher in the PAH group. VLs were undetectable at delivery in 60% of the PAH group compared with 88% of the BAH group. No cases of vertical transmission occurred. PAH women may be at a higher risk for HIV-related disease progression. This may increase vertical transmission risks. Further studies and interventions with this growing population are warranted.

Partial treatment interruption of protease inhibitor-based highly active antiretroviral therapy regimens in HIV-infected children.

Summary: Treatment guidelines for HIV-infected children recommend using combinations of reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). Successful suppression of HIV replication and adherence to these regimens are often suboptimal because of multiple factors. For patients with detectable viremia and limited treatment options, therapy simplification consisting of RTIs, referred to as partial treatment interruption (PTI), may represent a temporizing option. We describe a cohort of 26 HIV-infected children who underwent treatment simplification by discontinuing the PI and continuing therapy with 2 or more RTIs. The subjects, who were identified retrospectively, were followed for a period of 24 to 96 weeks. Data collected included clinical information, viral load, and CD4+T lymphocyte percentage (CD4%) at baseline and 24, 48, and 96 weeks after PTI. Twenty-six, 21, and 11 patients were evaluated at 24, 48, and 96 weeks, respectively. No child had Centers for Disease Control and Prevention-defined disease progression, and there were no significant changes in viral loads (P > 0.5) across all study intervals after interruption of the PIs. Although most children maintained a CD4% > 15%, comparisons of CD4% at 24 and 48 weeks demonstrated a statistically significant decrease compared with baseline. Therapy simplification by PTI may provide a practical option in patients intolerant of or failing PI-based highly active antiretroviral therapy.

Elevated levels of vitamin B12 and folate in vertically infected children with Hiv-1

Objective:Neurologic and hematologic abnormalities are common in HIV-infected children and may be related to concomitant deficiencies in serum B12 and folate, which are highly prevalent in HIV-infected adults. We sought to determine the prevalence of B12 and folate deficiencies in HIV-infected children in the United States. Methods:Cross-sectional information on demographics, folate and B12 levels, hematological parameters, concurrent CD4%, HIV-viral load and antiretroviral regimens were abstracted from the medical records of 103 vertically infected children followed in an outpatient pediatric HIV clinic in the Bronx, during 2001–2002. Results:Mean age was 10 years (±4.4 years), 46% were male, 53% African–American and 46% Hispanic. Nineteen percent had significant immunologic suppression and 18 children had AIDS. All were receiving combination antiretroviral therapy and 66% were on a protease inhibitor-based regimen. Sixteen were taking cotrimoxazole prophylaxis. None were taking multivitamins or manifested clinical evidence of gastrointestinal malabsorption. All patients had serum folate or B12 levels within or above the normal range. Children with elevated B12 were significantly more likely to be younger (P = 0.0002) and have higher mean folate levels (P = 0.0004) compared with children with normal serum B12. In a multivariate logistic regression analysis, factors independently associated with elevated levels of vitamin B12 included: elevated serum folate [odds ratio (OR): 3.2; P = 0.01], nonnucleoside reverse transcriptase inhibitor use (OR: 0.38; P = 0.05) and female sex (OR: 0.67; P = 0.42) Conclusion:Folate and B12 deficiencies are uncommon in HIV-infected children in the United States, suggesting that routine supplementation with B12 and folate is not indicated without confirmation of micronutrient deficiency.

FcγRIIa polymorphism in human immunodeficiency virus-infected children with invasive pneumococcal disease

Invasive pneumococcal disease (IPD) occurs frequently in HIV-infected children and adults. Defects in complement function, opsonic capsular antibodies, and Fc receptor antibody-mediated phagocytosis could contribute to impaired host defense against Streptococcus pneumoniae. The objective of this study was to define the distribution of the three FcγRIIa genotypes in HIV+ children, including those with IPD. Forty-eight HIV+ Hispanic children, including eight with IPD, followed at Bronx-Lebanon Hospital Center, Bronx, New York, nine HIV+ adults with IPD, and 56 HIV- Hispanic control subjects were studied. The children and adults were identified retrospectively except for one child who developed IPD during the study. FcγRIIa genotypes were determined by PCR amplification of the FcγRIIa locus from genomic DNA samples and hybridization of the PCR products with allele-specific oligonucleotides. Naturally occurring serum antibodies reactive with four pneumococcal polysaccharide serotypes were determined by ELISA in seven of eight children with IPD. There were no statistical differences in FcγRIIa genotypes between HIV+ children with and without IPD, HIV+ adults with IPD, or HIV- Hispanics. The predominant IgG subclass of pneumococcal polysaccharide binding antibodies in the seven HIV+ children with IPD studied was IgG1. The distribution of FcγRIIa genotypes in HIV+ children with and without IPD is similar to that of the normal Hispanic population. The prospect of passive immunotherapy with specific anticapsular antibodies might be a promising alternative for the treatment and/or prevention of IPD in HIV+ children and other immunodeficient groups.

Impact of HIV-1 infection and pregnancy on maternal health: comparison between perinatally and behaviorally infected young women.

Background The introduction of combination antiretroviral therapy has resulted in improved survival and quality of life for individuals infected with the human immunodeficiency virus (HIV). There is, as expected, a growing population of perinatally HIV-infected women who are, have been, or will become pregnant. We describe a large cohort of perinatally infected women, compare it with a similar age-matched behaviorally HIV-infected group, and examine factors affecting maternal and infant health. Methods We reviewed the records of 30 perinatally infected women who gave birth at two hospitals between January 2000 and December 2011. The comparison group comprised behaviorally infected women who delivered at these hospitals during the same period. The outcome measures were differences in CD4 counts and viral load between the cohorts, and comparisons of maternal morbidity, mortality, and mother-to-child HIV transmission. Results Median CD4 counts were significantly lower in the perinatal group before, during, and after pregnancy. The median viral load was significantly higher in the perinatal group. Interval prepregnancy to post partum viral load decline was also greater in the behavioral group. Viral load decreases in the perinatal population were not sustained in the post partum period, at which time viral load trended back to prepregnancy levels. There was one mother-to-child HIV transmission in a perinatally infected woman. Over an extended 4 years of follow-up, there were four deaths in the perinatal group and none in the behavioral group. Conclusion After delivery, the differences between perinatally and behaviorally infected mothers accentuate, with immunologic deterioration in the former group. The perinatal population may require novel management strategies to ensure outcomes comparable with those observed in the behavioral group.

Profile of darunavir in the treatment of HIV-infected pediatric and adolescent patients.

The introduction of protease inhibitors (PI) containing antiretroviral regimens in the treatment of HIV infection in infants, children, and adolescents has dramatically decreased morbidity and mortality. Darunavir, the latest PI to be FDA approved for pediatric patients older than 6 years and currently the preferred PI for use in adult patients, was added as an alternative PI for use in children based on a combination of data from both adult and pediatric trials. This review of darunavir in the treatment of HIV-infected children and adolescents looks at the major published clinical trials findings, pharmacokinetic and resistance studies, and preliminary data on use in younger children.

Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults with Human Immunodeficiency Virus Infection Being Treated with Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial

Background Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033). Conclusions For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status. Clinical Trials Registration NCT01751646.