Explore the vast range of titles available.

HLA class I molecules are ligands for killer cell immunoglobin like receptors (KIR) that control the antiviral response of natural killer (NK) cells. However, the effects of KIR and HLA (KIR/HLA) alleles on HIV disease of children have not been studied. 993 antiretroviral naïve children with symptomatic HIV infection from PACTG protocols P152 and P300 were genotyped for KIR and HLA alleles using the Luminex platform. Linear regression was used to test the association between genotypes and baseline pre-ART HIV RNA, CD4+ lymphocyte count, and cognitive score, adjusting for age, race/ethnicity and study. The interaction between genetic markers and age was investigated. To account for multiple testing the false discovery rate (FDR) was controlled at 0.05. Children with the KIR2DS4*ALL FULL LENGTH (KIR2DS4*AFL) allele had higher CD4+ lymphocyte counts. Among children ≤2 years of age, the KIR2DS4*AFL was associated with lower plasma HIV RNA and higher cognitive index scores. KIR Cent2DS3/5_1 had lower CD4+ lymphocyte counts in children ≤2 years of age, while the presence of Tel1, Tel2DS4_2, Tel2DS4_4, Tel8, Tel2DS4_6 had higher CD4+ lymphocyte counts in all children. Presence of Cent2, Cent4 and Cent8 was associated with increased HIV RNA load in children ≤2 years. Presence of KIR3DL1+Bw4 was associated with higher CD4+ lymphocyte counts in all children. Among children >2 years old, KIR3DS1+Bw4-80I was associated with higher plasma HIV RNA, and Bw6/Bw6 was associated with lower plasma HIV RNA compared to children with KIR3DS1+Bw4-80I. Presented data show for the first time that specific KIR alleles independently or combined with HLA ligands are associated with HIV RNA and CD4+ lymphocyte counts in infected, antiretroviral naive children; and many of these effect estimates appear to be age dependent. These data support a role for specific KIR alleles in HIV pathogenesis in children.

We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children. Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1. At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets. HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load. ClinicalTrials.gov NCT00992836.

Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNγ-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells (Bexhaust). IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but decreased Teff responses to the vaccine. The proportions of immature and transitional B cells did not affect the responses to vaccine. Increased Bact were associated with high Bmem responses to the vaccine.

In this randomized, controlled trial in Africa and India, combination antiretroviral therapy was more effective than standard therapy in preventing mother-to-child transmission of HIV but was associated with increased toxic effects. Antiretroviral regimens used for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV) have evolved from the first successful trial that used zidovudine single-drug prophylaxis in 1994 to current triple-drug regimens. 1 , 2 Although there are clear benefits of combination antiretroviral therapy (ART) for the mother and infant, these do not come without risks; some studies have shown higher rates of adverse pregnancy outcomes with maternal ART than with regimens containing fewer antiretroviral agents. 3 – 5 The Promoting Maternal and Infant Survival Everywhere (PROMISE) trial compared the relative efficacy and safety of various proven antiretroviral strategies for the prevention of . . .

Human immunodeficiency virus (HIV) type 1 DNA in peripheral blood mononuclear cells (PBMC) was quantified in 31 children who received efavirenz, nelfinavir, and 1 or 2 nucleoside reverse-transcriptase inhibitors for ⩾2 years and in whom undetectable plasma HIV-1 RNA levels (<50 copies/mL) were sustained, to determine the usefulness of HIV-1 DNA as a marker of virus suppression. The median baseline HIV-1 DNA level was 750 copies/106 PBMC. After initiation of highly active antiretroviral therapy (HAART), HIV-1 DNA levels decreased gradually, reaching a plateau from week 80 through week 104 (median HIV-1 DNA level, 263 copies/ 106 PBMC). Children who had plasma HIV-1 RNA levels <50 copies/mL after receiving HAART for 8 weeks (n = 16) had persistently lower quantities of intracellular HIV-1 DNA than children whose HIV-1 RNA levels reached <50 copies/mL after 8 weeks of HAART (n = 15). The median half-life for intracellular HIV-1 DNA was 60 weeks. Thus, despite prolonged maintenance of undetectable levels of plasma HIV-1 RNA, HIV-1 DNA remains detectable in PBMC of children and may be a useful marker of further virus suppression.

Background. Pregnant women infected with human immunodeficiency virus (HIV) may have particular vulnerability to 2009 pandemic H1N1 influenza (pH1N1) infection. The safety and immunogenicity of pH1N1 vaccination in HIV-infected pregnant women are unknown. Methods. HIV-infected women 18–39 years of age and 14–34 weeks' gestation on antiretroviral therapy received two 30-μg doses of unadjuvanted, inactivated pH1N1 vaccine 21 days apart. Hemagglutination inhibition titers were measured at entry, 21 days after dose 1, and 10 and 21 days after dose 2, and, in mothers and infants, at delivery and 3 and 6 months postdelivery. Results. No severe vaccine-related adverse events were observed among 127 subjects. At entry, 21% had seroprotective (≥1:40) titers. Seroprotection and seroresponse (≥4-fold rise) occurred in 73% and 66% after dose 1 and 80% and 72% after dose 2, respectively. Of women lacking seroprotection at entry, 66% attained seroprotection after dose 1 and 75% after dose 2. Seroprotective titers were present in 67% of mothers and 65% of infants at delivery (median 66 days after dose 2), 60% of mothers and 26% of infants at 3 months postdelivery, and 59% of mothers and 12% of infants at 6 months postdelivery. Conclusions. Two 30-μg doses were moderately immunogenic in HIV-infected pregnant women. No concerning vaccine-related safety signals were observed. Seroprotection persisted in most women postpartum. Efficient transplacental antibody transfer occurred, but seroprotection in infants waned rapidly. Vaccination to protect HIV-infected pregnant women and their newborns from new influenza strains is feasible, but more immunogenic platforms should be evaluated. Clinical Trials Registration. NCT00992017.

Background. Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)—infected children in the absence of highly active antiretroviral therapy (HAART). Methods. HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30 000 copies/cL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4—5 years later, and PRN antibody was measured before and 7 and 28 days later. Results. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4—5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Conclusions. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. Clinical Trials Registration: NCT000013871 (www.clinicaltrials.gov).

Background. The safety and immunogenicity of high-dose pandemic H1N1 (pH1N1) vaccination in perinatally human immunodeficiency virus type 1 (HIV-1)—infected children, adolescents, and young adults are unknown. Methods. Two 30-μg doses of 2009 Novartis pH1N1 monovalent vaccine (Fluvirin) were administered 21—28 days apart to perinatally HIV-1—infected children, adolescents, and young adults. Antibodies were measured by hemagglutination inhibition (HAI) assay at baseline, 21—28 days after first vaccination, 7—13 days after the second vaccination, and 7 months after the first vaccination. Results. Among the 155 participants, 54 were aged 4—8 years, 51 were aged 9—17 years, and 50 were aged 18—24 years. After 2 doses of Fluvirin, seroresponse (≥4-fold rise in HAI titers) was demonstrated in 79.6%, 84.8%, and 83% of participants in the aforementioned age groups, respectively, and seroprotection (HAI titers ≥40) was shown in 79.6%, 82.6%, and 85.1%, respectively. Of those lacking seroresponse (n = 43) or seroprotection (n = 37) after the first vaccination, 46.5% and 40.5% achieved seroresponse or seroprotection, respectively, after the second vaccination. Among participants who lacked seroprotection at entry, a \"complete response\" (both seroresponse and seroprotection) after first vaccination was associated with higher baseline log 10 HAI titer and non-Hispanic ethnicity. No serious vaccine-related events occurred. Conclusion. Two doses of double-strength pH1N1 vaccine are safe and immunogenic and may provide improved protection against influenza in perinatally HIV-1—infected children and youth. Clinical Trials Registration. NCT00992836.

BackgroundHepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)–infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated MethodsHIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received ⩾3 doses of HBV vaccine were given an HBV vaccine booster. Concentrations of antibody to hepatitis B surface antigen (anti-HBs) were determined before vaccination and at weeks 8, 48, and 96. A subset of subjects was administered a subsequent dose, and anti-HBs was measured before and 1 and 4 weeks later ResultsAt entry, 24% of 204 subjects were seropositive. Vaccine response occurred in 46% on the basis of seropositivity 8 weeks after vaccination and in 37% on the basis of a ⩾4-fold rise in antibody concentration. Of 69 subjects given another vaccination 4–5 years later, immunologic memory was exhibited by 45% on the basis of seropositivity 1 week after vaccination and by 29% on the basis of a ⩾4-fold rise in antibody concentration at 1 week. Predictors of response and memory included higher nadir and current CD4 cell percentage, higher CD19 cell percentage, and undetectable HIV load ConclusionsHIV-infected children frequently lack protective levels of anti-HBs after previous HBV vaccination, and a significant proportion of them do not respond to booster vaccination or demonstrate memory despite receiving HAART, leaving this population insufficiently protected from infection with HBV Trial registrationClinicalTrials.gov identifier: NCT00013871