Maxwel Omenda - Academia.edu (original) (raw)

Papers by Maxwel Omenda

Research paper thumbnail of Clinical and Immunological Outcomes of HIV-Exposed Uninfected and HIV-Unexposed Uninfected Children in the First 24 Months of Life in Western Kenya

Background Previous studies show increased morbidity in children who are HIV-exposed but uninfect... more Background Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. Methods Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers with HIV received combination antiretroviral therapy. HEU children received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. Results HEU and HUU children had similar growth curves. HEU children had lower rates of malaria and respiratory illness. Trajectories of plasma cytokines and vaccine-specific antibodies were similar in HEU and HUU children. There were subtle difference...

Research paper thumbnail of Defining the Role of Maternal Plasma Neutralizing Antibodies in Mother-to-Child Transmission of HIV-1

Defining the Role of Maternal Plasma Neutralizing Antibodies in Mother-to-Child Transmission of H... more Defining the Role of Maternal Plasma Neutralizing Antibodies in Mother-to-Child Transmission of HIV-1 . Maxwel Majiwa Omenda Chair of the supervisory Committee: Affiliate Professor Julie Overbaugh Pathobiology & Microbiology Full Member: Division of Human Biology, Fred Hutchinson Cancer Research Center Identifying a vaccine that would elicit neutralizing antibodies (Nabs) that prevent HIV-1 infection of host cells is a priority for the HIV-1 research field. Mother-tochild transmission (MTCT) of HIV-1 offers a natural setting in which to evaluate whether Nabs are correlated with protection in exposed individuals. This topic is the focus of this thesis. Given that Nabs can impact MTCT of HIV-1 by neutralizing viruses within the mother and/or infants, I first evaluated in chapter 2 whether the Env specific Nabs repertoire in the mother correlates with that in their corresponding infants. I compared antibody levels in plasma from 60 mother-infant pairs near the time of birth, including ...

Research paper thumbnail of Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk

mBio, 2016

Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of p... more Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of protection. Neutralizing antibodies (NAbs) are suggested to contribute to a viral bottleneck during MTCT, but their role in blocking transmission is unclear, as studies comparing the NAb sensitivities of maternal viruses have yielded disparate results. We sought to determine whether transmitting mothers differ from nontransmitting mothers in the ability to neutralize individual autologous virus variants present at transmission. Ten transmitting and 10 nontransmitting HIV-infected mothers at high risk of MTCT were included in this study. Full-length HIV envelope genes ( n = 100) were cloned from peripheral blood mononuclear cells obtained near transmission from transmitting mothers and at similar time points from nontransmitting mothers. Envelope clones were tested as pseudoviruses against contemporaneous, autologous maternal plasma in neutralization assays. The association between transmi...

Research paper thumbnail of In-uteroinfection with HIV-1 associated with suppressed lymphoproliferative responses at birth

Clinical and Experimental Immunology, 2014

SummaryIn-utero exposure to HIV-1 may affect the immune system of the developing child and may in... more SummaryIn-utero exposure to HIV-1 may affect the immune system of the developing child and may induce HIV-1-specific immune responses, even in the absence of HIV-1 infection. We evaluated lymphoproliferative capacity at birth among 40 HIV-1-uninfected infants born to HIV-1-infected mothers and 10 infants who had acquired HIV-1 in utero. Cord blood mononuclear cells were assayed using [3H]-thymidine incorporation for proliferation in response to HIV-1 p55-gag and the control stimuli phytohaemagglutinin (PHA), Staphylococcus enterotoxin B (SEB) and allogeneic cells. In response to HIV-1 p55-gag, eight (20%) HIV-1-exposed, uninfected (EU) infants had a stimulation index (SI) ≥ 2 and three (30%) in-utero HIV-1 infected infants had SI ≥2. The frequency and magnitude of responses to HIV-1 p55-gag were low overall, and did not differ statistically between groups. However, proliferative responses to control stimuli were significantly higher in EU infants than in infants infected in utero, w...

Research paper thumbnail of Evidence for Efficient Vertical Transfer of Maternal HIV-1 Envelope–Specific Neutralizing Antibodies but No Association of Such Antibodies With Reduced Infant Infection

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013

Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. We compar... more Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. We compared antibody levels in plasma from 60 mother-infant pairs near the time of birth, including 14 breastfeeding transmission pairs. The Envelope binding titers were strongly correlated (r=0.91, p<0.0001) and similar (1.4-fold greater in maternal plasma) between a mother and her corresponding infant as were the neutralizing antibody (Nab) levels (r = 0.80, p<0.0001; 1.3-fold higher), suggesting efficient transfer. There was no significant difference in Nab responses between transmitting and non-transmitting mothers, although there was a trend for transmitting mothers to have higher HIV-1-specific Nabs.

Research paper thumbnail of HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype

AIDS, 2013

Rationale-To protect against HIV infection, passively transferred and/or vaccine elicited neutral... more Rationale-To protect against HIV infection, passively transferred and/or vaccine elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs. Method-To investigate whether variants transmitted during MTCT are generally resistant to HIV-1 specific NAbs, 107 maternal or infant variants representing the dominant HIV-1 subtypes were tested against six recently identified HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs), NIH45-46W, VRC01, PGT128, PGT121, PG9, and PGT145. Results-Infant and maternal variants did not differ in their neutralization sensitivity to individual bNAbs, nor did viruses from transmitting versus non-transmitting mothers, although there was a trend for viruses from transmitting mothers to be less sensitive overall. No single bNAb neutralized all viruses, but a combination of bNAbs that target distinct epitopes covered 100% of the variants tested. Compared to heterosexually transmitted variants, vertically transmitted variants, were significantly more sensitive to neutralization by PGT128 and PGT121 (p=0.03 in both cases) but there were no differences for the other bNAbs. Overall, subtype A variants were significantly more sensitive to NIH45-46 (p=0.04), VRC01 (p=0.002) and PGT145 (p=0.03) compared to the non-subtype A and less sensitive to PGT121 than subtype Cs (p=0.0001). Conclusion-A combination of bNAbs against distinct epitopes may be needed to provide maximum coverage against viruses in different modes of transmission and diverse subtypes.

Research paper thumbnail of Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya

Nutrients, 2016

Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes ... more Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation.

Research paper thumbnail of Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya

Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes ... more Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation.

Research paper thumbnail of Maternal Human Leukocyte Antigen A*2301 Is Associated with Increased Mother-to-Child HIV-1 Transmission

The Journal of Infectious Diseases, Oct 15, 2010

Research paper thumbnail of Immune Responses to Measles and Tetanus Vaccines Among Kenyan Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Children Pre- and Post-Highly Active Antiretroviral Therapy and Revaccination

The Pediatric Infectious Disease Journal, 2009

Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1... more Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1 (HIV-1)-infected children pre-and post-highly active antiretroviral therapy and revaccination

Research paper thumbnail of Latent Tuberculosis Detection by Interferon γ Release Assay during Pregnancy Predicts Active Tuberculosis and Mortality in Human Immunodeficiency Virus Type 1–Infected Women and Their Children

The Journal of Infectious Diseases, 2010

Background. We evaluated the prognostic usefulness of interferon g release assays (IGRAs) for act... more Background. We evaluated the prognostic usefulness of interferon g release assays (IGRAs) for active tuberculosis and mortality in Kenyan human immunodeficiency virus type 1 (HIV-1)-infected women and their infants. Methods. Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1-infected women. Hazard ratios, adjusted for baseline maternal CD4 cell count (aHR CD4), were calculated for associations between IGRA positivity and risk of active tuberculosis and mortality over 2-year postpartum follow-up among women and their infants. Results. Of 333 women tested, 52 (15.6%) had indeterminate IGRA results. Of the remaining 281 women, 120 (42.7%) had positive IGRA results, which were associated with a 4.5-fold increased risk of active tuberculosis (aHR CD4 , 4.5; 95% confidence interval [CI], 1.1-18.0;). For immunosuppressed women (CD4 cell count, P p .030 !250 cells/mL), positive IGRA results were associated with increased risk of maternal mortality (aHR CD4 , 3.5; 95% CI, 1.02-12.1;), maternal active tuberculosis or mortality (aHR CD4 , 5.2; 95% CI, 1.7-15.6;), and P p .045 P p .004 infant active tuberculosis or mortality overall (aHR CD4 , 3.0; 95% CI, 1.0-8.9;) and among HIV-1-exposed P p .05 uninfected infants (aHR CD4 , 7.3; 95% CI, 1.6-33.5;). P p .01 Conclusions. Positive IGRA results for HIV-1-infected pregnant women were associated with postpartum active tuberculosis and mortality among mothers and their infants. Tuberculosis and human immunodeficiency virus type 1 (HIV-1) infection significantly increase maternal and infant mortality [1-3]. In resource-limited settings, the greatest burden of tuberculosis among women occurs

Research paper thumbnail of Maternal Human Leukocyte Antigen A*2301 Is Associated with Increased Mother‐to‐Child HIV‐1 Transmission

The Journal of Infectious Diseases, 2010

Research paper thumbnail of CCR2-64I Polymorphism Is Associated With Lower Maternal HIV-1 Viral Load and Reduced Vertical HIV-1 Transmission

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2009

Research paper thumbnail of CCR5, RANTES and SDF-1 polymorphisms and mother-to-child HIV-1 transmission

International Journal of Immunogenetics, 2010

Among 288 HIV-1-infected, breastfeeding women who received zidovudine prophylaxis and were follow... more Among 288 HIV-1-infected, breastfeeding women who received zidovudine prophylaxis and were followed with their infants in Nairobi, we found no associations between maternal genetic polymorphisms in CCR5 (59029G/A, 59353T/C, 59356T/C, 59402G/A), RANTES (−403G/A), and SDF-1 (3′801G/A) and mother-to-child HIV-1 transmission; plasma, cervical, and breastmilk viral loads; or breastmilk chemokine concentrations.

Research paper thumbnail of Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition

Clinical & Experimental Immunology, 2009

Summary Infants infected with HIV-1 after the first month of life have a lower viral set-point an... more Summary Infants infected with HIV-1 after the first month of life have a lower viral set-point and slower disease progression than infants infected before 1 month. We investigated the kinetics of HIV-1-specific CD8+ T lymphocyte secretion of interferon (IFN)-γ in infants infected before 1 month of life compared with those infected between months 1 and 12 (late infection). HIV-1 infection was assessed at birth and at months 1, 3, 6, 9 and 12 and timing of infection was determined by HIV-1 gag DNA from dried blood spots and verified by plasma HIV-1 RNA levels. HIV-1 peptide-specific IFN-γ responses were measured by enzyme-linked immunospot at months 1, 3, 6, 9 and 12. Timing of development of IFN-γ responses was compared using the log–rank test and Kaplan–Meier survival curves. Infants infected late developed HIV-1-specific CD8+ T cell responses 2·8 months sooner than infants infected peripartum: 2·3 versus 5·1 months after HIV-1 infection (n = 52, P = 0·04). Late-infected infants had...

Research paper thumbnail of Longitudinal Comparison of Chemokines in Breastmilk Early Postpartum Among HIV-1-Infected and Uninfected Kenyan Women

Breastfeeding Medicine, 2007

Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and alte... more Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and altered risk of mother-to-child HIV-1 transmission. To characterize CC and CXC chemokines in breastmilk postpartum, we collected breastmilk specimens at regular intervals for 6 months after delivery from women with and without HIV-1 infection and used commercial ELISA kits to measure breastmilk concentrations of MIP-1α, MIP-1β, RANTES, and SDF-1α. Among 54 HIV-1-infected and 26 uninfected women, mean chemokine levels were compared crosssectionally and longitudinally at days 5 and 10, and months 1 and 3 postpartum. For both HIV-1infected and uninfected women, breastmilk chemokine levels were highest at day 5 for MIP-1α, MIP-1β, and SDF-1α, and subsequently decreased. RANTES levels remained constant over the follow-up period among HIV-1-uninfected women, and increased moderately among HIV-1infected women. For MIP-1β and RANTES, breastmilk levels were significantly higher among HIV-1-infected women compared to uninfected women early postpartum. In addition, HIV-1infected women transmitting HIV-1 to their infant had consistently higher breastmilk RANTES levels than those who did not transmit, with the greatest difference observed at 1 month (2.68 vs. 2.21 log 10 pg/mL, respectively; p = 0.007). In summary, all four chemokines were most elevated within the first month postpartum, a period of high transmission risk via breastmilk. MIP-1β and RANTES levels in breastmilk were higher among HIV-1-infected women than among uninfected women, and breastmilk RANTES was positively associated with vertical transmission in this study, consistent with results from our earlier cohort.

Research paper thumbnail of Evaluation of a single round polymerase chain reaction assay using dried blood spots for diagnosis of HIV-1 infection in infants in an African setting

BMC Pediatrics, 2011

Background The aim of this study was to develop an economical 'in-house' single round pol... more Background The aim of this study was to develop an economical 'in-house' single round polymerase chain reaction (PCR) assay using filter paper-dried blood spots (FP-DBS) for early infant HIV-1 diagnosis and to evaluate its performance in an African setting. Methods An 'in-house' single round PCR assay that targets conserved regions in the HIV-1 polymerase (pol) gene was validated for use with FP-DBS; first we validated this assay using FP-DBS spiked with cell standards of known HIV-1 copy numbers. Next, we validated the assay by testing the archived FP-DBS (N = 115) from infants of known HIV-1 infection status. Subsequently this 'in-house' HIV-1 pol PCR FP-DBS assay was then established in Nairobi, Kenya for further evaluation on freshly collected FP-DBS (N = 186) from infants, and compared with findings from a reference laboratory using the Roche Amplicor® HIV-1 DNA Test, version 1.5 assay. Results The HIV-1 pol PCR FP-DBS assay could detect one HIV-1 provir...

Research paper thumbnail of Clinical and Immunological Outcomes of HIV-Exposed Uninfected and HIV-Unexposed Uninfected Children in the First 24 Months of Life in Western Kenya

Background Previous studies show increased morbidity in children who are HIV-exposed but uninfect... more Background Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. Methods Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers with HIV received combination antiretroviral therapy. HEU children received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. Results HEU and HUU children had similar growth curves. HEU children had lower rates of malaria and respiratory illness. Trajectories of plasma cytokines and vaccine-specific antibodies were similar in HEU and HUU children. There were subtle difference...

Research paper thumbnail of Defining the Role of Maternal Plasma Neutralizing Antibodies in Mother-to-Child Transmission of HIV-1

Defining the Role of Maternal Plasma Neutralizing Antibodies in Mother-to-Child Transmission of H... more Defining the Role of Maternal Plasma Neutralizing Antibodies in Mother-to-Child Transmission of HIV-1 . Maxwel Majiwa Omenda Chair of the supervisory Committee: Affiliate Professor Julie Overbaugh Pathobiology & Microbiology Full Member: Division of Human Biology, Fred Hutchinson Cancer Research Center Identifying a vaccine that would elicit neutralizing antibodies (Nabs) that prevent HIV-1 infection of host cells is a priority for the HIV-1 research field. Mother-tochild transmission (MTCT) of HIV-1 offers a natural setting in which to evaluate whether Nabs are correlated with protection in exposed individuals. This topic is the focus of this thesis. Given that Nabs can impact MTCT of HIV-1 by neutralizing viruses within the mother and/or infants, I first evaluated in chapter 2 whether the Env specific Nabs repertoire in the mother correlates with that in their corresponding infants. I compared antibody levels in plasma from 60 mother-infant pairs near the time of birth, including ...

Research paper thumbnail of Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk

mBio, 2016

Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of p... more Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of protection. Neutralizing antibodies (NAbs) are suggested to contribute to a viral bottleneck during MTCT, but their role in blocking transmission is unclear, as studies comparing the NAb sensitivities of maternal viruses have yielded disparate results. We sought to determine whether transmitting mothers differ from nontransmitting mothers in the ability to neutralize individual autologous virus variants present at transmission. Ten transmitting and 10 nontransmitting HIV-infected mothers at high risk of MTCT were included in this study. Full-length HIV envelope genes ( n = 100) were cloned from peripheral blood mononuclear cells obtained near transmission from transmitting mothers and at similar time points from nontransmitting mothers. Envelope clones were tested as pseudoviruses against contemporaneous, autologous maternal plasma in neutralization assays. The association between transmi...

Research paper thumbnail of In-uteroinfection with HIV-1 associated with suppressed lymphoproliferative responses at birth

Clinical and Experimental Immunology, 2014

SummaryIn-utero exposure to HIV-1 may affect the immune system of the developing child and may in... more SummaryIn-utero exposure to HIV-1 may affect the immune system of the developing child and may induce HIV-1-specific immune responses, even in the absence of HIV-1 infection. We evaluated lymphoproliferative capacity at birth among 40 HIV-1-uninfected infants born to HIV-1-infected mothers and 10 infants who had acquired HIV-1 in utero. Cord blood mononuclear cells were assayed using [3H]-thymidine incorporation for proliferation in response to HIV-1 p55-gag and the control stimuli phytohaemagglutinin (PHA), Staphylococcus enterotoxin B (SEB) and allogeneic cells. In response to HIV-1 p55-gag, eight (20%) HIV-1-exposed, uninfected (EU) infants had a stimulation index (SI) ≥ 2 and three (30%) in-utero HIV-1 infected infants had SI ≥2. The frequency and magnitude of responses to HIV-1 p55-gag were low overall, and did not differ statistically between groups. However, proliferative responses to control stimuli were significantly higher in EU infants than in infants infected in utero, w...

Research paper thumbnail of Evidence for Efficient Vertical Transfer of Maternal HIV-1 Envelope–Specific Neutralizing Antibodies but No Association of Such Antibodies With Reduced Infant Infection

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013

Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. We compar... more Little is known about the efficiency of vertical transfer of HIV-1-specific antibodies. We compared antibody levels in plasma from 60 mother-infant pairs near the time of birth, including 14 breastfeeding transmission pairs. The Envelope binding titers were strongly correlated (r=0.91, p<0.0001) and similar (1.4-fold greater in maternal plasma) between a mother and her corresponding infant as were the neutralizing antibody (Nab) levels (r = 0.80, p<0.0001; 1.3-fold higher), suggesting efficient transfer. There was no significant difference in Nab responses between transmitting and non-transmitting mothers, although there was a trend for transmitting mothers to have higher HIV-1-specific Nabs.

Research paper thumbnail of HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype

AIDS, 2013

Rationale-To protect against HIV infection, passively transferred and/or vaccine elicited neutral... more Rationale-To protect against HIV infection, passively transferred and/or vaccine elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs. Method-To investigate whether variants transmitted during MTCT are generally resistant to HIV-1 specific NAbs, 107 maternal or infant variants representing the dominant HIV-1 subtypes were tested against six recently identified HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs), NIH45-46W, VRC01, PGT128, PGT121, PG9, and PGT145. Results-Infant and maternal variants did not differ in their neutralization sensitivity to individual bNAbs, nor did viruses from transmitting versus non-transmitting mothers, although there was a trend for viruses from transmitting mothers to be less sensitive overall. No single bNAb neutralized all viruses, but a combination of bNAbs that target distinct epitopes covered 100% of the variants tested. Compared to heterosexually transmitted variants, vertically transmitted variants, were significantly more sensitive to neutralization by PGT128 and PGT121 (p=0.03 in both cases) but there were no differences for the other bNAbs. Overall, subtype A variants were significantly more sensitive to NIH45-46 (p=0.04), VRC01 (p=0.002) and PGT145 (p=0.03) compared to the non-subtype A and less sensitive to PGT121 than subtype Cs (p=0.0001). Conclusion-A combination of bNAbs against distinct epitopes may be needed to provide maximum coverage against viruses in different modes of transmission and diverse subtypes.

Research paper thumbnail of Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya

Nutrients, 2016

Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes ... more Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation.

Research paper thumbnail of Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya

Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes ... more Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation.

Research paper thumbnail of Maternal Human Leukocyte Antigen A*2301 Is Associated with Increased Mother-to-Child HIV-1 Transmission

The Journal of Infectious Diseases, Oct 15, 2010

Research paper thumbnail of Immune Responses to Measles and Tetanus Vaccines Among Kenyan Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Children Pre- and Post-Highly Active Antiretroviral Therapy and Revaccination

The Pediatric Infectious Disease Journal, 2009

Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1... more Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1 (HIV-1)-infected children pre-and post-highly active antiretroviral therapy and revaccination

Research paper thumbnail of Latent Tuberculosis Detection by Interferon γ Release Assay during Pregnancy Predicts Active Tuberculosis and Mortality in Human Immunodeficiency Virus Type 1–Infected Women and Their Children

The Journal of Infectious Diseases, 2010

Background. We evaluated the prognostic usefulness of interferon g release assays (IGRAs) for act... more Background. We evaluated the prognostic usefulness of interferon g release assays (IGRAs) for active tuberculosis and mortality in Kenyan human immunodeficiency virus type 1 (HIV-1)-infected women and their infants. Methods. Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1-infected women. Hazard ratios, adjusted for baseline maternal CD4 cell count (aHR CD4), were calculated for associations between IGRA positivity and risk of active tuberculosis and mortality over 2-year postpartum follow-up among women and their infants. Results. Of 333 women tested, 52 (15.6%) had indeterminate IGRA results. Of the remaining 281 women, 120 (42.7%) had positive IGRA results, which were associated with a 4.5-fold increased risk of active tuberculosis (aHR CD4 , 4.5; 95% confidence interval [CI], 1.1-18.0;). For immunosuppressed women (CD4 cell count, P p .030 !250 cells/mL), positive IGRA results were associated with increased risk of maternal mortality (aHR CD4 , 3.5; 95% CI, 1.02-12.1;), maternal active tuberculosis or mortality (aHR CD4 , 5.2; 95% CI, 1.7-15.6;), and P p .045 P p .004 infant active tuberculosis or mortality overall (aHR CD4 , 3.0; 95% CI, 1.0-8.9;) and among HIV-1-exposed P p .05 uninfected infants (aHR CD4 , 7.3; 95% CI, 1.6-33.5;). P p .01 Conclusions. Positive IGRA results for HIV-1-infected pregnant women were associated with postpartum active tuberculosis and mortality among mothers and their infants. Tuberculosis and human immunodeficiency virus type 1 (HIV-1) infection significantly increase maternal and infant mortality [1-3]. In resource-limited settings, the greatest burden of tuberculosis among women occurs

Research paper thumbnail of Maternal Human Leukocyte Antigen A*2301 Is Associated with Increased Mother‐to‐Child HIV‐1 Transmission

The Journal of Infectious Diseases, 2010

Research paper thumbnail of CCR2-64I Polymorphism Is Associated With Lower Maternal HIV-1 Viral Load and Reduced Vertical HIV-1 Transmission

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2009

Research paper thumbnail of CCR5, RANTES and SDF-1 polymorphisms and mother-to-child HIV-1 transmission

International Journal of Immunogenetics, 2010

Among 288 HIV-1-infected, breastfeeding women who received zidovudine prophylaxis and were follow... more Among 288 HIV-1-infected, breastfeeding women who received zidovudine prophylaxis and were followed with their infants in Nairobi, we found no associations between maternal genetic polymorphisms in CCR5 (59029G/A, 59353T/C, 59356T/C, 59402G/A), RANTES (−403G/A), and SDF-1 (3′801G/A) and mother-to-child HIV-1 transmission; plasma, cervical, and breastmilk viral loads; or breastmilk chemokine concentrations.

Research paper thumbnail of Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition

Clinical & Experimental Immunology, 2009

Summary Infants infected with HIV-1 after the first month of life have a lower viral set-point an... more Summary Infants infected with HIV-1 after the first month of life have a lower viral set-point and slower disease progression than infants infected before 1 month. We investigated the kinetics of HIV-1-specific CD8+ T lymphocyte secretion of interferon (IFN)-γ in infants infected before 1 month of life compared with those infected between months 1 and 12 (late infection). HIV-1 infection was assessed at birth and at months 1, 3, 6, 9 and 12 and timing of infection was determined by HIV-1 gag DNA from dried blood spots and verified by plasma HIV-1 RNA levels. HIV-1 peptide-specific IFN-γ responses were measured by enzyme-linked immunospot at months 1, 3, 6, 9 and 12. Timing of development of IFN-γ responses was compared using the log–rank test and Kaplan–Meier survival curves. Infants infected late developed HIV-1-specific CD8+ T cell responses 2·8 months sooner than infants infected peripartum: 2·3 versus 5·1 months after HIV-1 infection (n = 52, P = 0·04). Late-infected infants had...

Research paper thumbnail of Longitudinal Comparison of Chemokines in Breastmilk Early Postpartum Among HIV-1-Infected and Uninfected Kenyan Women

Breastfeeding Medicine, 2007

Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and alte... more Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and altered risk of mother-to-child HIV-1 transmission. To characterize CC and CXC chemokines in breastmilk postpartum, we collected breastmilk specimens at regular intervals for 6 months after delivery from women with and without HIV-1 infection and used commercial ELISA kits to measure breastmilk concentrations of MIP-1α, MIP-1β, RANTES, and SDF-1α. Among 54 HIV-1-infected and 26 uninfected women, mean chemokine levels were compared crosssectionally and longitudinally at days 5 and 10, and months 1 and 3 postpartum. For both HIV-1infected and uninfected women, breastmilk chemokine levels were highest at day 5 for MIP-1α, MIP-1β, and SDF-1α, and subsequently decreased. RANTES levels remained constant over the follow-up period among HIV-1-uninfected women, and increased moderately among HIV-1infected women. For MIP-1β and RANTES, breastmilk levels were significantly higher among HIV-1-infected women compared to uninfected women early postpartum. In addition, HIV-1infected women transmitting HIV-1 to their infant had consistently higher breastmilk RANTES levels than those who did not transmit, with the greatest difference observed at 1 month (2.68 vs. 2.21 log 10 pg/mL, respectively; p = 0.007). In summary, all four chemokines were most elevated within the first month postpartum, a period of high transmission risk via breastmilk. MIP-1β and RANTES levels in breastmilk were higher among HIV-1-infected women than among uninfected women, and breastmilk RANTES was positively associated with vertical transmission in this study, consistent with results from our earlier cohort.

Research paper thumbnail of Evaluation of a single round polymerase chain reaction assay using dried blood spots for diagnosis of HIV-1 infection in infants in an African setting

BMC Pediatrics, 2011

Background The aim of this study was to develop an economical 'in-house' single round pol... more Background The aim of this study was to develop an economical 'in-house' single round polymerase chain reaction (PCR) assay using filter paper-dried blood spots (FP-DBS) for early infant HIV-1 diagnosis and to evaluate its performance in an African setting. Methods An 'in-house' single round PCR assay that targets conserved regions in the HIV-1 polymerase (pol) gene was validated for use with FP-DBS; first we validated this assay using FP-DBS spiked with cell standards of known HIV-1 copy numbers. Next, we validated the assay by testing the archived FP-DBS (N = 115) from infants of known HIV-1 infection status. Subsequently this 'in-house' HIV-1 pol PCR FP-DBS assay was then established in Nairobi, Kenya for further evaluation on freshly collected FP-DBS (N = 186) from infants, and compared with findings from a reference laboratory using the Roche Amplicor® HIV-1 DNA Test, version 1.5 assay. Results The HIV-1 pol PCR FP-DBS assay could detect one HIV-1 provir...