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WHAT'S NEW THIS THURSDAY: ABSTRACTS ON VACCINATION FROM THE WASHINGTON AIDS CONFERENCE

Wednesday, 25th of July 2012

 

• ABSTRACTS ON VACCINATION FROM THE WASHINGTON AIDS CONFERENCE

 

For a searchable database of abstracts from the Washington AIDS conference of this week, go to http://pag.aids2012.org/PAGHome.aspx?tab=2

 

• THE EFFECTS OF MEASLES ON DISEASE MARKERS IN HIV+ CHILDREN AND ADOLESCENTS LIVING IN BOTSWANA 

Presented by Elizabeth R Wolf (Botswana).

E.R. Wolf^1,2, K.E. Wirth³, A. Ho-Foster⁴, D. Goldfarb⁵, M. Tolle⁶, I. Makone⁷, C. Jacovides⁸, M. Chise¹, A.P. Steenhoff<sup>4,9

1</sup>University of Botswana School of Medicine, Gaborone, Botswana, ²University of Washington, Seattle, United States, ³Harvard School of Public Health, Cambridge, United States, ⁴Botswana-UPenn Partnership, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States, ⁵McMaster University, Hamilton, Canada, ⁶Baylor College of Medicine International Pediatric AIDS Initiative, Houston, United States, ⁷Princess Marina Hospital, Gaborone, Botswana, ⁸University of Pennsylvania Perelman School of Medicine, Philadelphia, United States, ⁹Children's Hospital of Philadelphia, Philadelphia, United States

Also accessible at http://pag.aids2012.org/abstracts.aspx?aid=14589

 

Background: It has been proposed that the mechanism of HIV viral load (VL) reduction during acute measles is through suppression of CD4 cell proliferation. Our study examined the effect of measles on CD4% and VL of HIV+ children and adolescents in Botswana during the 2009-2010 measles epidemic.
Methods: We retrospectively examined the records of 2,011 pediatric (0-18 years) HIV+ patients attending the Botswana-Baylor Children's Clinical Center of Excellence for measles infection. Measles cases were classified by a positive measles IgM or by meeting clinical criteria for measles as defined by the World Health Organization. We used linear regression with generalized estimating equations to assess the effect of measles on CD4% and log VL. We adjusted for age, sex, nutritional status, WHO stage, and exposure to and duration of antiretroviral therapy (ART).
Results: We identified 195 measles cases (45.6% male) with median age of 13.2 years (interquartile range (IQR): 10.3-15.3). Baseline median CD4% was 29% (IQR: 23%-35%). Of cases, 85% were on ART, of whom 97% had an undetectable (< 400 copies/mL) VL at baseline. Two deaths (case fatality rate (CFR) = 1%) were felt to be measles related.


[Measles cases (n=195) in the study population]


Amongst cases, CD4% declined by 5.5 percentage points (95% CI: 0.1-11.0) in the first month following measles. By 6 months post-measles, we found no significant difference in CD4% compared to baseline (P = 0.44). In patients without measles, CD4% remained stable over the entire study period. We found no significant difference in log VL between pre- and post-measles visits (P = 0.11).
Conclusions: Measles was associated with a significant but temporary CD4% immunosuppression among a cohort of HIV+ children and adolescents living in Botswana, most of who were on ART. This may help explain the significant morbidity of measles in HIV+ patients, even amongst those who are virologically suppressed. CFR in the cohort, however, was low.

• SUSCEPTIBILITY TO MEASLES AMONG PERINATALLY HIV-POSITIVE ADOLESCENTS AND YOUNG ADULTS 

L. Morris¹, R. Posada¹, C. Hickman², D. Latner², T. Singh³, A. Rautenberg³, J. Jao⁴, W. Bellini², R. Sperling<sup>3

1</sup>Mount Sinai School of Medicine, Division of Pediatric Infectious Disease, New York, United States, ²Centers for Disease Control & Prevention, Division of Viral Diseases, Atlanta, United States, ³Mount Sinai School of Medicine, Department of OB/Gyn, New York, United States, ⁴Mount Sinai School of Medicine, Division of Infectious Disease, New York, United States

Also accessible at http://pag.aids2012.org/abstracts.aspx?aid=14088

 

Background: Many youth with perinatally acquired HIV (PAH) exhibit poor immune responses to vaccinations, including measles, mumps and rubella (MMR). This has worldwide public health implications, particularly in areas with high prevalence of HIV and measles. The objective of this pilot study was to determine the prevalence of measles immunity among individuals with PAH and prior MMR vaccination.
Methods: Individuals with PAH >13 years old, receiving care at Mount Sinai Hospital (MSH), New York with prior MMR vaccination were enrolled. Measles IgG titers were determined at MSH via commercially available ELISA and at the Centers for Disease Control and Prevention, Atlanta by plaque reduction neutralization (PRN) assay. Measles immunity was defined as IgG titers >120mIU by PRN assay. Medical records were reviewed for demographics and pertinent clinical data. P-values were calculated using Wilcoxon test, Chi-square or Fisher's exact test as appropriate.
Results: Based on PRN assay, only 6/34 (17.6%) subjects were measles immune. Measles immune subjects were younger [median age 14.5 vs. 19 years (p=0.01)]. Differences in gender and race/ethnicity were not statistically significant between immune and non-immune groups [65% vs. 50% female (p=0.648) and 79% vs. 67% Black or Hispanic (p=0.802) respectively].

	Measles Non-Immune (n = 28)	Measles Immune (n = 6)	p-value
Age, years (Median) (IQR)	19 (17-20)	14.5 (13-18)	0.01
Female, No. (%)	19 (65%)	3 (50%)	0.648
Race/Ethnicity, No. (%)			0.802
White	1 (4%)	0 (0%)
African American	7 (24%)	1 (17%)
Hispanic	16 (55%)	3 (50%)
Other	5 (17%)	2 (33%)

• [Table 1: Baseline Demographics]
  
  
  One (17%) measles immune subject had a history of opportunistic infections compared to 18 (62%) non-immune subjects (p=0.07). Median CD4 count at enrollment and nadir CD4 count were 682 cells/mm³ and 299 cells/mm³ in measles immune subjects vs. 263 cells/mm³ (p=0.054) and 143 cells/mm³ (p=0.175) in non-immune subjects, respectively. Additionally, 83% immune subjects received antiretroviral therapy at vaccination compared to 30% non-immune subjects (p=0.025).

Measles Non-Immune (n = 28)	Measles Immune (n = 6)	p-value
18 (62%)	1 (17%)	0.07
143 (23-231)	299 (34-442)	0.175
14 (3-25)	25 (7-41)	0.227
3.74 (3.18-4.3)	2.79 (1.22-4.36)	0.159
2 (1-4)	2 (2-3)	0.618
12 (11-18)	13.5 (11-15)	0.873

 

·       PREVALENCE AND CORRELATES OF PROTECTIVE MEASLES ANTIBODY IN HIV-POSITIVE KENYAN CHILDREN ON HAART 

L. Newman¹, L. Ben-Youssef¹, A. Gatuguta², A. Njoroge³, M. Merkel¹, Q. Ton¹, D. Wamalwa³, B. Payne¹, C. Farquhar<sup>1

1</sup>University of Washington, Seattle, United States, ²Kenyatta University, Nairobi, Kenya, ³University of Nairobi, Nairobi, Kenya

Also accessible at http://pag.aids2012.org/abstracts.aspx?aid=18697

Background: The HIV epidemic has the potential to exacerbate measles morbidity and mortality, as HIV reduces both initial and sustained responses to measles vaccination. Studies have suggested that highly active antiretroviral treatment (HAART) is unable to restore measles immune responses in HIV-infected children who had been previously vaccinated. To establish guidelines for re-vaccination, it is essential to determine whether there is sustained protection against measles in HIV-infected children on HAART.
Methods: A prospective cohort study based at Kenyatta National Hospital in Nairobi enrolled HIV-infected children on HAART with a CD4%>15. Caregivers were interviewed and blood was obtained from children for measles antibody, CD4%, and complete blood count measures. Measles IgG antibody status was determined using ELISA (Siemans, USA). Correlates of positive antibody responses were determined using independent t-tests and multivariate logistic regression. Equivocal measles antibody results were classified as negative.
Results: All ninety-eight HIV-infected children reported measles vaccination before age 12 months. Mean time on HAART was 3.5 years (range 0.5-12.5), mean age was 6.5 years (range 1.1-11.1), and 48 (49%) were male at enrolment. Forty (41%) of the 98 children had positive measles IgG results, 40 (41%) were negative, and 18 (18%) had equivocal results. Children under age 6 were more likely to have protective measles antibody (OR=2.53, 95%CI 1.05-6.12, p-value=0.039). There was no statistically significant association between CD4% or gender and a positive result, though the median CD4% was higher, and more females than males had protective antibody titers (34% vs. 31%; 60% vs. 45%, respectively). Time on HAART was not associated with antibody results.
Conclusions: Among HIV-infected Kenyan children with immune reconstitution on HAART, only 41% had protective levels of measles antibody at baseline. Continued follow-up for 2 years after these children are re-vaccinated will determine optimal timing and immunization guidelines for HIV-infected children on HAART.

 

 

• SEROCONVERSION RATES IN HIV-POSITIVE CHILDREN AND ADOLESCENTS RECEIVING DOUBLE DOSE HEPATITIS B VACCINE AFTER INITIAL NON-RESPONSE TO STANDARD REGIMEN 

Presented by Katherine Dickman Dobbs (United States).

K. Dickman Dobbs¹, C. Moloney², E.R. Cooper<sup>2

1</sup>Boston Medical Center, Pediatrics, Boston, United States, ²Boston Medical Center, Pediatric Infectious Diseases, Boston, United States

Also accessible at http://pag.aids2012.org/abstracts.aspx?aid=1146

 

Background: Co-infection with hepatitis B virus (HBV) is an important cause of morbidity and mortality for HIV-infected patients. Compared to the HIV-uninfected population, children with HIV have shown lower rates of seroconversion after receiving the HBV vaccine series, varying from 20-78%, in comparison to 95-99%. Revaccination with double dose (DD) HBV vaccine has been shown to improve seroconversion rates in some populations, including those on hemodialysis and HIV-infected adults with high CD4 counts and relative viral suppression.
Methods: Our pediatric HIV clinic instituted a quality improvement measure in which patients who had not responded to initial standard dose vaccine series or subsequent booster doses (defined as HBsAb< 10 IU/L) were administered a three-dose series of DD HBV vaccine for age, at intervals of no less than 8 weeks. HBsAb levels were measured after first, second, and third DD. Baseline clinical characteristics were compared between responders and non-responders to the DD series.
Results: Sixty of 99 patients previously immunized with HBV (60.6%) were identified as having HBsAb levels < 10 IU/L after chart review. As of February 2012, 54 of these 60 have had one or more DD. The seroconversion rate after receiving one or more DD was 65.7%. As compared to non-responders, responders were younger (15.4 vs. 19.1 years, p=0.04), had lower average BMI (22.8 vs. 26.6 kg/m², p=0.04), higher CD4 counts (766 vs. 487 cells/mm³, p=0.02), higher CD4 percentages (31.5% vs. 21.9%, p=0.004), and lower median viral loads (75 vs. 1491 copies/ml, p=0.05).
Conclusions: Revaccination using DD HBV vaccine improves seroconversion rates among HIV-infected children and adolescents with previous non-response to standard dose series. Investigation is needed to determine if this would be an effective first strategy, or if its success represents a booster effect suggesting past memory. Further study is needed for development of policy regarding immunization against HBV in HIV-infected children. 

 

 

• IMMUNOGENICITY OF ORAL LIVE ATTENUATED HUMAN ROTAVIRUS VACCINE GIVEN AS TWO DOSES (10 AND 14 WEEKS) IN HIV-INFECTED, HIV-EXPOSED-UNINFECTED AND HIV-UNEXPOSED-UNINFECTED INFANTS IN SOUTH AFRICA 

A. Koen¹, L. Jose¹, N. Govender¹, C. Cutland¹, F. Shafi², N. François³, J.P. Yarzabal³, M. Hezareh³, M. Moreira³, D. Borys³, L. Schuerman³, S.A. Madhi<sup>1,4

1</sup>University of the Witwatersrand, Medical Research Council, Respiratory and Meningeal Pathogens Research Unit and Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases, Johannesburg, South Africa, ²GlaxoSmithKline Pharmaceuticals, Bangalore, India, ³GlaxoSmithKline Biologicals, Wavre, Belgium, ⁴National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Center for Vaccines and Immunology, Johannesburg, South Africa

Also accessible at http://pag.aids2012.org/abstracts.aspx?aid=21226

Background: HIV-infected (HIV+) infants are at increased risk of diarrheal associated morbidity and mortality. There are limited published data on immune responses to rotavirus vaccines in HIV+ infants, and none in relation to a two-dose schedule of oral live attenuated human rotavirus vaccine (HRV, GlaxoSmithKline Biologicals). We evaluated the immune responses to HRV in HIV+, HIV-exposed-uninfected (HEU) and HIV-unexposed-uninfected (HUU) infants following two doses of HRV when given concurrently with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GlaxoSmithKline Biologicals) and other recommended childhood vaccines.
Methods: In a phase III, open-label, single-center, controlled trial (NCT00829010) in South Africa, HIV+, HEU and HUU infants received two or three primary PHiD-CV doses at 6, (10), 14 weeks of age. After study start rotavirus vaccination was included in the South-African immunization program; HRV was therefore added as a study vaccine (through protocol amendment) and given at 10, 14 weeks of age. Sera were analyzed for anti-rotavirus IgA pre-vaccination and one month following the second HRV dose. HIV+ infants were managed with triple antiretroviral therapy per national guidelines.
Results: Of 446 infants (72 HIV+; 90 HEU; 284 HUU) in the according-to-protocol immunogenicity cohort (based on PHiD-CV vaccination), 327 received two HRV doses. An increase in anti-rotavirus IgA seropositivity rates (concentration ≥20 U/mL) and geometric mean concentrations (GMCs) was observed from pre- to post-vaccination in all three groups (Table). The post-vaccination seropositivity rate appeared lower in HIV+ (58.3%) than HUU subjects (71.9%) as did the post-vaccination antibody GMC (52.1 U/mL in HIV+ compared to 99.9 U/mL in HUU).



[Table]


Conclusions: Post-vaccination anti-rotavirus IgA concentrations and seropositivity rates tended to be lower in HIV+ infants than in HUU infants. The immunogenicity results were in line with those following a three-dose primary series of HRV in HIV+ infants from a previous study (NCT00263666).
Funding: GlaxoSmithKline Biologicals