Effect of HIV Infection Status and Anti‐Retroviral Treatment on Quantitative and Qualitative Antibody Responses to Pneumococcal Conjugate Vaccine in Infants

Madhi, Shabir А.; Adrian, Peter V.; Cotton, Mark F.; McIntyre, James; Jean‐Philippe, Patrick; Meadows, Shawn; Nachman, Sharon; Käyhty, Helena; Klugman, Keith P.; Violari, Avye

doi:10.1086/653704

Cited by 91 publications

(101 citation statements)

References 13 publications

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“…This is important, as, for example, a study comparing responses to the 7-valent pneumococcal vaccine in HEU and HUU infants showed similar responses in HEU and HUU infants for 6 of 7 serotypes and an even better response than HUU infants to one serotype (6B). However, upon evaluation of qualitative function by the opsonophagocytic killing assay, HEU infants in fact required higher concentrations of antibody for 50% killing activity against one of the serotypes (19F) (34). Thus, we cannot exclude qualitative differences between HEU and HUU infants to the EPI vaccines we tested.…”

Section: Discussionmentioning

confidence: 97%

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Reikie

Naidoo

Ruck

et al. 2013

Clin Vaccine Immunol

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e HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from infection. The possibility exists that altered response to vaccination contributes to the higher rate of infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following the WHO extended program on immunization (EPI).Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total IgG and antibodies specific for Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine antibodies (maternal antibodies passively acquired) specific for tetanus were lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and HepB vaccination. HEU demonstrated stronger pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life.

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Section: Discussionmentioning

confidence: 97%

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Reikie

Naidoo

Ruck

et al. 2013

Clin Vaccine Immunol

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“…12 The majority of infants (349/92%) co-enrolled on a study evaluating the effect of ART strategy on response to conjugated 7-valent pneumococcal and Haemophilus influenzae B vaccines. 13 …”

Section: Methodsmentioning

confidence: 99%

Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial

et al. 2013

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Background Interim results from the CHER trial showed that early antiretroviral therapy (ART) was life-saving for HIV-infected infants. Given limited options and potential for toxicity with life-long ART, CHER compared early limited ART with deferred ART. Methods CHER was an open 3-arm trial in HIV-infected asymptomatic infants aged <12 weeks with CD4% ≥25%. Infants were randomized to deferred (ART-Def) or immediate ART for 40weeks (ART-40W) or 96weeks (ART-96W), followed by interruption. Criteria for ART initiation in ART-Def and re-initiation after interruption were CD4% <25% in infancy; otherwise <20% or CDC severe stage B or stage C disease. Lopinavir-ritonavir, zidovudine, lamivudine was the first-line regimen at ART initiation and re-initiation. The primary endpoint was time-to-failure of first-line ART (immunological/clinical/virological) or death. Comparisons were by intent-to-treat, using time-to-event methods. Findings 377 infants were enrolled: median age 7.4weeks; CD4% 35% and HIV RNA log 5.7copies/ml. Median follow-up was 4.8 years; 34 (9%) were lost-to-follow-up. Median time to ART initiation in ART-Def was 20 (IQR 16–25) weeks. Time to restarting ART after interruption was 33 (26–45) weeks in ART-40W and 70 (35–109) weeks in ART-96W; at trial end 19% and 32% respectively, remained off ART. Proportions of follow-up time spent on ART were 81%, 70% and 69% in ART-Def, ART-40W and ART-96W arms. 48/125(38%), 32/126(25%) and 26/126(21%) children reached the primary endpoint; hazard ratio (95%CI), relative to ART-Def, was 0.59(0.38-0.93, p=0.02) for ART-40W and 0.47(0.27-0.76, p=0.002) for ART-96W. Seven children (3 ART-Def, 3 ART-40W, 1 ART-96W) switched to second-line ART. Interpretation Early limited ART had superior clinical/immunological outcome with no evidence of excess disease progression during subsequent interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption with marginally better outcomes.

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“…This cross-sectional sub-study compared neurodevelopmental outcomes among participants in CHER randomised to early versus deferred ART, and among HIV-uninfected infants (HIV-exposed and HIV-unexposed) participating in a linked vaccine study[11]. Children were eligible for inclusion if they had no dysmorphic syndromes or underlying non-HIV-related central nervous system (CNS) abnormalities.…”

Section: Methodsmentioning

confidence: 99%

Early antiretroviral therapy improves neurodevelopmental outcomes in infants

Laughton

Cornell

Grové

et al. 2012

Aids

164

141

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Objectives To evaluate the effect of early versus deferred antiretroviral therapy (ART) on neurodevelopment of infants from Cape Town participating in the CHER (Children with HIV Early Antiretroviral Therapy) trial. Design HIV-infected infants were randomised to early (<3 months) or deferred ART. HIV-uninfected infants (HIV-exposed and HIV-unexposed) provide background data. Methods Neurological examination and Griffiths Mental Development Scales (GMDS) were administered between 10–16 months of age, by testers blind to HIV status and randomised allocation. Mean quotients were compared using paired t-tests. Results 64 infants on early ART and 26 on deferred ART (of potential 77 and 38 respectively on CHER trial) were assessed at median age 11 months (range 10-16). On the GMDS, all scores were lower in the deferred arm and the General Griffiths and Locomotor Scores were significantly lower: mean (standard deviation): 100.1 (13.8) vs 106.3 (10.6) p=0.02; and 88.9 (16.3) vs 97.7 (12.5), p<0.01, respectively. Children with HIV who received early ART performed as well as children without HIV except on the locomotor subscale. Both infected and uninfected mean GMDS scores were within the average range. Conclusions Infants initiated on early ART have significantly better Locomotor and General Scores on the GMDS at median age 11 months compared to infants on deferred ART, despite careful monitoring and ready access to ART in the latter.

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Effect of HIV Infection Status and Anti‐Retroviral Treatment on Quantitative and Qualitative Antibody Responses to Pneumococcal Conjugate Vaccine in Infants

Cited by 91 publications

References 13 publications

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial

Early antiretroviral therapy improves neurodevelopmental outcomes in infants

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