MATERNAL IMMUNE RESPONSES AND RISK OF INFANT INFECTION WITH HIV-1 AFTER A SHORT COURSE ZIDOVUDINE IN A COHORT OF HIV-1 INFECTED PREGNANT WOMEN IN RURAL KENYA

Objective: To investigate the effects of short-course nucleoside reverse transcriptaseinhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infantinfection with HIV-1 among rural-based mothers in western Kenya.Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers andtheir infants.Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant womenand their infants.Methods: After informed consent, the women were enrolled at gestation age between16-24 weeks. For cultural and economic reasons, all mothers were allowed to breastfeed their infants. Short-course antepartum regime of AZT was administered to allmothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+T cell subset assays were performed before 3rd trimester (about 36 weeks gestation)and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samplessequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 monthsof age.Interventions: Antepartum short-course orally administered AZT: 300mg twice-dailystarting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mgevery three hours during labour until delivery.Main Outcome Measures: Maternal CD4+ T cell counts before and after AZT treatment.Determination of infant HIV-1 infection status.Results: Among 107 women sampled, only 59 received full dose of AZT and thus qualifiedfor present analysis. Of these, 12 infected their children with HIV, while 47 did not.Comparison of CD4+ T cells before and after AZT treatment scored a significant risein all mothers (P = 0.01). This increase in CD4+ T cells was not significant amongmothers who infected their infants with HIV-1 (P = 0.474). However, a significant risein CD4+ T cells following AZT therapy was observed only in mothers who did nottransmit HIV-1 to their infants (P=0.014).Conclusion: These data suggest that a rise in the CD4+ T cell counts following shortAZT regimen, now widely in use in resource-weak countries, may be evidence of theactive suppression of the replication of HIV. However, further studies to examine themulti-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need tobe carried out to help fully explain the effect of AZT on immune response and whetherthe CD4+T cell count can be used as a true test of immunological normalisation duringantiretroviral therapy

MEETING REPORT: UNESCO-MERCK AFRICA RESEARCH SUMMIT 2015- ACCELERATING ACCESS AND SUSTAINING INNOVATION 'FROM AFRICA FOR AFRICA'.

Background: The Ebola virus disease outbreak of 2014 was the largest, longest and most devastating in the history of the disease. It demonstrated the social and economic impact an emerging infectious disease can have in a globalized world. Health systems in affected countries were stretched to the point of near collapse, while social relations and traditional practices were negatively impacted. Heads of African research institutions, African government representatives, leaders of global pharmaceutical companies, global infectious disease experts and close to 100 young African researchers from 25 countries; Assembled in Geneva on 19 and 20th October 2015, for the inaugural UNESCO-Merck Africa Summit sponsored by the United Nations Educational, Science and Culture Organization and Merck KGA Goal of Summit: The primary goal of the summit was to develop strategies to increase health research capacity in Africa, with special focus on Ebola and enhancing pandemic preparation for emerging infectious diseases. The summit was also provide a forum to showcase the research taking place in Africa, and provided platform for African researchers to network. Some of the key issues discussed included; strategies for enhancing policy frameworks to promote knowledge translation, strengthening of health systems, enhancing knowledge and data sharing, and increasing innovation in Africa. Conclusions: Summit attendees recognized that Africa still bore the heaviest burden of infectious disease, and increased commitment by African governments to fund health research, offered the best hope for developing health solutions and interventions to improve the health of Africans. Improved health in turn would enhance the productivity of Africans, further supporting the socio-economic transformation currently taking place on the contine

CD4T Lymphocyte subsets and disease manifestation in children with and without HIV born to HIV-1 infected mothers

Objective:To understand the natural history of HIV-1 infection in children in terms of evolution of childhood clinical manifestations versus the immune status, we prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 for two years between March 1998 and March 2000. Design:A prospective cohort study. Setting:An institutional children's home. Subjects:Fifty nine children (26 males and 33 females) with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 and adopted in institutional children home. Methods:HIV-1 status of children under nine months was confirmed by polymerase chain reaction (PCR). ELISA for HIV-1 antibody in serum/plasma was used to confirm HIV-infection status for children aged £18 months. Children were visited every three months between March and June 2000. At every visit blood was collected for total white cell count, haemoglobin and CD4+ and CD8+ T cell counts. The institutional doctor routinely examined children and treated all ailments. Clinical data were recorded. Measures: HIV-DNA, anti-HIV antibodies, total white blood count, total T cell counts, CD4 and CD8 T cell subset counts, frequency of childhood manifestations of infection. Results:The children were aged between 4.5 and 13 years. The baseline haematological and immunological profiles (mean, mode) were: HIV-1 sero-converters (WBC 7151,7150; HB 11.6, 12.0; CD4+ 686, 795; CD8+ 2168, 1507) and HIV-1 de-seroconverters (mean, mode) were: (WBC 8386, 7150; HB 11.7, 12.8; CD4+ 735, 795; CD8+ 2168, 1507). The commonest causes of illnesses among the HIV-1 children were URTI (85.3%), TB(56.1%), pneumonia (56.2%), tonsillitis (34.1%), parotiditis (28%) and acute otitis media (25%). The distribution of clinical manifestations was similar between the two categories of children, except URTI, whose prevalence was significantly increased among HIV-1 infected children (p-value=0.006). Among the HIV-1 infected children, only TB, parotiditis, and acute otitis media (AOM) were significantly associated with decreased CD4+ T cell count (

CD4T LYMPHOCYTE SUBSETS AND DISEASE MANIFESTATION IN CHILDREN WITH AND WITHOUT HIV BORN TO HIV-1 INFECTED MOTHERS

ABSTRACTObjective: To understand the natural history of HIV-1 infection in children in termsof evolution of childhood clinical manifestations versus the immune status, we prospectivelystudied children with and without maternally transmitted HIV-1 infection born tomothers infected with HIV-1 for two years between March 1998 and March 2000.Design: A prospective cohort study.Setting: An institutional children’s home.Subjects: Fifty nine children (26 males and 33 females) with and without maternallytransmitted HIV-1 infection born to mothers infected with HIV-1 and adopted ininstitutional children home.Methods: HIV-1 status of children under nine months was confirmed by polymerasechain reaction(PCR). ELISA for HIV-1 antibody in serum/plasma was used to confirmHIV-infection status for children aged £18 months. Children were visited every threemonths between March and June 2000. At every visit blood was collected for total whitecell count, haemoglobin and CD4+ and CD8+ T cell counts. The institutional doctorroutinely examined children and treated all ailments. Clinical data were recorded.Measures: HIV-DNA, anti-HIV antibodies, total white blood count, total T cell counts,CD4 and CD8 T cell subset counts, frequency of childhood manifestations of infection.Results: The children were aged between 4.5 and 13 years. The baseline haematologicaland immunological profiles (mean, mode) were: HIV-1 sero-converters (WBC 7151,7150;HB 11.6, 12.0; CD4+ 686, 795; CD8+ 2168, 1507) and HIV-1 de-seroconverters (mean,mode) were: (WBC 8386, 7150; HB 11.7, 12.8; CD4+ 735, 795; CD8+ 2168, 1507). Thecommonest causes of illnesses among the HIV-1 children were URTI (85.3%), TB(56.1%),pneumonia (56.2%), tonsillitis (34.1%), parotiditis (28%) and acute otitis media (25%).The distribution of clinical manifestations was similar between the two categories ofchildren, except URTI, whose prevalence was significantly increased among HIV-1infected children (p-value=0.006). Among the HIV-1 infected children, only TB,parotiditis, and acute otitis media (AOM) were significantly associated with decreasedCD4+ T cell count (p<0.05) resulting from HIV infection.Conclusions: HIV infection in children predisposes them to common childhood infectionsthat can be used as markers of immune decline. TB, AOM, URTI may be early indicatorsof suspicion that would enable selective screening for HIV infection in children

MATERNAL IMMUNE RESPONSES AND RISK OF INFANT INFECTION WITH HIV-1 AFTER A SHORT COURSE ZIDOVUDINE IN A COHORT OF HIV-1 INFECTED PREGNANT WOMEN IN RURAL KENYA

ABSTRACTObjective: To investigate the effects of short-course nucleoside reverse transcriptaseinhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infantinfection with HIV-1 among rural-based mothers in western Kenya.Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers andtheir infants.Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant womenand their infants.Methods: After informed consent, the women were enrolled at gestation age between16-24 weeks. For cultural and economic reasons, all mothers were allowed to breastfeed their infants. Short-course antepartum regime of AZT was administered to allmothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+T cell subset assays were performed before 3rd trimester (about 36 weeks gestation)and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samplessequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 monthsof age.Interventions: Antepartum short-course orally administered AZT: 300mg twice-dailystarting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mgevery three hours during labour until delivery.Main Outcome Measures: Maternal CD4+ T cell counts before and after AZT treatment.Determination of infant HIV-1 infection status.Results: Among 107 women sampled, only 59 received full dose of AZT and thus qualifiedfor present analysis. Of these, 12 infected their children with HIV, while 47 did not.Comparison of CD4+ T cells before and after AZT treatment scored a significant risein all mothers (P = 0.01). This increase in CD4+ T cells was not significant amongmothers who infected their infants with HIV-1 (P = 0.474). However, a significant risein CD4+ T cells following AZT therapy was observed only in mothers who did nottransmit HIV-1 to their infants (P=0.014).Conclusion: These data suggest that a rise in the CD4+ T cell counts following shortAZT regimen, now widely in use in resource-weak countries, may be evidence of theactive suppression of the replication of HIV. However, further studies to examine themulti-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need tobe carried out to help fully explain the effect of AZT on immune response and whetherthe CD4+T cell count can be used as a true test of immunological normalisation duringantiretroviral therapy