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Mother-to-infant vertical transmission of HIV usually occurs during pregnancy, labor, delivery or breastfeeding. It is the third leading cause of transmission of HIV after sexual intercourse and blood transfusions. In 2008, 12 million women aged 15 years and above were anticipated to be living with HIV in countries within Sub-Saharan Africa. In this study, the association between parental HIV knowledge, attitudes and risk reduction practices, and HIV vertical transmission in Kenya were explored. The health belief model was used to help understand and interpret the findings. For this quantitative study, data were collected via surveys from 212 participants in 3 HIV clinics in Kenya. Data were analyzed using descriptive and inferential statistics. Around 45% of respondents lacked knowledge on key aspects of Prevention of Mother to Child Transmission (PMTCT) of HIV particularly on expressing and heat treating milk from HIV positive mothers to make it safe for their babies. About 65% of Participants had awareness towards Mother to Child Transmission (MTCT) of HIV. Logistic regression showed no association between socioeconomic factors and parental knowledge on MTCT of HIV. Logistic modeling found that there was association between attitude and MTCT, revealing that attitude increased the likelihood to influence MTCT. Being married was associated with reduced risk of MTCT of HIV. The overall results indicated gaps in knowledge and information packaging. The potential positive social change implication of this study is that factors related to HIV vertical transmission identified in this study might be utilized to develop and implement HIV prevention strategies to reduce HIV vertical transmission and decrease associated morbidity and mortality among this vulnerable population.

Thesis (MCur)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: The impact of infant feeding practices in the prevention of mother-to-childtransmission of HIV raised concerns in the field of health services. Breast feeding adds an additional 15-30% risk of HIV transmission to the infant; therefore, mothers who are HIV-positive are in need of information regarding safe infant feeding. A descriptive design for this particular study was applied with a primary quantitative approach. A convenient sample of sixty (n=60) participants between the ages of 15 – 37 were taken from subjects that enrolled in the prevention of mother-to-child transmission (PMTCT) programme in Onandjokwe district. The sample formed 85% of the target population (N=71). A structured questionnaire with closed and openended questions was used and completed by the researcher. Ethical approval for the study was obtained from the Ethics Committee at the Faculty of Health Sciences, University of Stellenbosch. Permission to conduct the research was obtained from the Ministry of Health and Social Services, Namibia, and the Onandjokwe district Hospital. A pilot study was conducted that constituted 25% of the sample. Validity and reliability was insured by the pilot study and the consultation of an expert in HIV research and an expert in nursing research. The presentation of results was mostly descriptive in nature by using frequency tables and a pie chart. The results showed that all participants (n=60/100%) were offered HIV counselling and testing during antenatal care. Mothers who were HIV positive knew that there is a possibility that the baby might be infected through breast milk. Furthermore, the study found that 70% (n=42) of participants used breast feeding exclusively, 20% (n=12) used replacement feeding and 10% (n=6) used mixed feeding practices. It was concluded that pregnant women and mothers known to be HIV-infected should be informed of the infant feeding practice recommended by the national or subnational authority to improve HIV-free survival of HIV-exposed infants. This includes information about the risks and benefits of various infant feeding options based on local assessments and guidance in selecting the most suitable option for their own situation. / AFRIKAANSE OPSOMMING: Die invloed van voedingspraktyke vir babas by die voorkoming van moeder-na-kindoordrag van die menslike immuungebrekvirus (MIV) het kommer op die gebied van gesondheidsdienste laat ontstaan. Borsvoeding dra ’n addisionele 15–30% risiko van MIV-oordrag tot die baba by en daarom benodig moeders wat MIV-positief is inligting ten opsigte van veilige voeding van hulle babas. 'n Beskrywende ontwerp vir hierdie besondere studie is gebruik tesame met 'n primêr kwantitatiewe benadering. 'n Gerieflikheidsteekproef van sestig (n=60) deelnemers tussen die ouderdomme 15–37 jaar is gekies uit persone wat ingeskryf het vir die voorkoming van moeder-na-kind-oordrag (VMNKO) program in Onandjokwe-distrik. Die steekproef het 85% van die teikenpopulasie (N=71) uitgemaak. 'n Gestruktureerde vraelys met geslote en oop vrae is gebruik en deur die navorser voltooi. Etiese goedkeuring vir die studie is verkry van die Etiese Kommitee van die Fakulteit Gesondheidswetenskappe, Universiteit Stellenbosch. Toestemming om die navorsing te doen, is verkry van die Ministerie van Gesondheid en Maatskaplike Dienste, Namibië, en die Onandjokwe Distrikshospitaal. 'n Loodsstudie is onderneem wat 25% van die steekproef behels het. Geldigheid en betroubaarheid is verseker deur die loodsstudie en oorlegpleging met 'n kundige op die gebied van MIV-navorsing en 'n kundige in verpleegnavorsing. Die aanbieding van resultate was meestal deskriptief van aard deur van frekwensietabelle en 'n sektordiagram gebruik te maak. Die resultate het getoon dat MIV-berading en -toetsing gedurende voorgeboortesorg aan alle deelnemers (n=60/100%) aangebied is. Moeders wat MIV-positief is, het geweet dat daar 'n moontlikheid bestaan dat die baba moontlik deur moedersmelk geïnfekteer kan word. Verder het die studie bevind dat 70% (n=42) van deelnemers uitsluitlik borsvoeding gebruik, 20% (n=12) gebruik ’n vervanging vir moedersmelk en 10% (n=6) gebruik gemengde voedingspraktyke. Daar is tot die slotsom gekom dat swanger vroue en moeders van wie bekend is dat hulle MIV-geïnfekteer is, ingelig behoort te word oor die babavoedingspraktyk aanbeveel deur die nasionale of subnasionale owerheid vir die verbetering van MIVvrye oorlewing van babas wat aan die MIV blootgestel is. Dit sluit in inligting oor die risiko’s en voordele van verskeie babavoedingsopsies gebaseer op plaaslike assesserings en leiding ten opsigte van die kies van die geskikste opsie vir hulle eie situasie.

Between 1994 to 1998 the ANRS 049a DITRAME trial was conducted during which a short regimen of ZDV demonstrated for the first time acceptability, tolerance and efficacy on reduction of mother-to-child transmission (MTCT). Our major aim was to analyze certain virological characteristics of infected women in this cohort and their association to HIV-1 transmission. On the one hand, we analyzed the HIV-1 replication capacity in different physiological compartments : blood, vaginal fluids (VF) and breast milk (BM) related to MTCT were investigated by nested case control studies in the DITRAME cohort. We demonstrated the relationship between plasma viral load (VL), at 34 weeks of amenorrheae and at Day 8 post partum, and MTCT in Africa where the probability to be exclusively breastfed for an one year infant is 46.6%. We also analyzed relationship between plasma VL and ZDV treatment. Additionally, we demonstrated that MTCT is essentially the consequence of a high proviral load in VF in our context. Moreover, reduced levels of HIV-1 RNA in milk at Day 8 were observed in mothers receiving ZDV therapy rather than in mothers under placebo. For the first time, the association between BMVL and postnatal transmission has been studied. We observed a highly significative difference between BMVL of women who transmitted the virus and those who did not. Moreover, univariate and multivariate analyzes clearly indicated that early breastfeeding log10 HIV-RNA at Day8 is an independent factor significatively associated to MTCT. Decreased median BMVL from 1608 copies/mL (c/ml) at Day8 to 346 c/ml at Day45 were found for mothers who transmitted the virus during the postpartum and who received placebo. Nevertheless, for those who received ZDV, median BMVL increased from 56 c/ml at Day8 to 470.5 c/ml at Day45. This marked trend to a rebound effect of BMVL could be the consequence of the treatment withdrawal as observed for adults at HAART withdrawal. On the other hand, we studied the variability of HIV and its association with MTCT. First, we analyzed HIV-1 diversity in African women in France and Burkina Faso. In a second step, we demonstrated that HMA was an adapted tool for co and super-infections studies for adults. By this way, we identified two superinfections among 147 women within our commercial sex workers cohort. Additionally, we used this tool to analyze children of the DITRAME cohort who were infected in utero and who could be superinfected during the delivery or later by breastfeeding. We identified seven children, among 18 who were infected in utero, displaying HMA profiles suspicions for co-infections, and who had a more important mortality rate than normally. Their proviral env sequences are currently analyzed. Moreover, we confirmed the fact that the rate of vitamin A has no influence on MTCT. De 1994 à 1998, s’est déroulé l’essai clinique DITRAME ANRS 049a qui a démontré, pour la première fois, l’acceptabilité, la tolérance et l’efficacité d’un traitement court de zidovudine (ZDV) sur la diminution de la TME. Notre travail s’est inscrit dans le cadre de cet essai et a eu pour but d’en analyser certains des aspects virologiques et leur rapport avec la transmission de la mère à l’enfant du VIH (TME). D’une part, nous avons analysé les niveaux de réplication virale dans différents compartiments physiologiques : le sang, les sécrétions cervico-vaginales (SCV) et le lait maternel (LM) et leur rapport avec la transmission, par des études cas-témoins nichées dans la cohorte DITRAME. Nous avons démontré le rapport entre la charge virale libre (CV) dans le plasma à 34 semaines d’aménorrhée et à J8 postpartum et la TME dans le contexte africain où la probabilité d’avoir un allaitement exclusif à un an est de 46,6%, et analysé leur rapport avec le traitement ZDV. Nous avons également démontré que la TME est essentiellement due à une charge provirale plus élevée dans les SCV dans notre contexte. De plus, grâce à la mise au point d’une technique, nous avons démontré que la ZDV avait un effet global marqué sur la diminution de la CV libre dans le LM. Il s’agit de la première étude mettant en relation la CV dans le lait avec la transmission postnatale. De même, nous avons observé une différence très hautement significative entre les charges virales libres des femmes ayant transmis le VIH et les non transmettrices. De plus, nos analyses univariée et multivariée démontrent que la CVlm mesurée en log10 de la lactation précoce (J8) est un facteur indépendant très significativement associé à la TME. Chez les femmes ayant transmis le virus durant le post-partum et non traitées à la ZDV, la CVlm médiane a décru de 1608 copies/mL (c/ml) à J8 à 346 c/ml à J45. Par contre, chez les femmes ayant transmis le virus mais ayant reçu un traitement ZDV, la CVlm médiane évolue de 56 c/ml à J8 à 470,5 c/ml à J45. Cette tendance marquée à un effet rebond de la CVlm à J45 laisse penser que la TME qui a lieu chez les femmes traitées à la ZDV pourrait être une conséquence de l’arrêt de ce traitement, comme observé chez les adultes après arrêt du traitement HAART. D’autre part, nous avons étudié la variabilité du VIH en fonction de la TME. Dans un premier temps, nous avons analysé la diversité du VIH-1 chez des mères africaines vivant en France, et par après au Burkina Faso. Ensuite, grâce à l’élaboration d’une nouvelle technique, nous avons démontré que le HMA pouvait être un outil adapté à l’étude des co- et sur-infection chez l’adulte. Nous avons identifié de cette manière deux surinfections parmi 147 femmes analysées au sein d’une cohorte de femmes à haut risque de surinfection. Nous avons ensuite utilisé ce moyen pour étudier des enfants de la cohorte DITRAME infectés in utero qui auraient pu se surinfecter durant le peripartum ou ensuite par l’allaitement. Sept enfants parmi 18 analysés, présentant des profils HMA à suspicion de coinfection et qui présentaient un taux de mortalité plus élevé que la normale, ont été identifiés. Leurs séquences provirales env sont en cours d’analyse actuellement. Par ailleurs, nous avons confirmé le fait que le taux de vitamine A n’a pas d’influence sur la TME.

Despite expansive scale-up of prevention of mother-to-child transmission (PMTCT) of HIV services in Kenya over the last decade, Kenya remains one of the countries contributing high numbers of children living with HIV globally and among the 22 PMTCT global plan priority countries. Using a mixed methods approach this study examined enabling factors –individual, social and structural – that enhance utilization of and adherence to PMTCT services in a plural urban setting in Kenya. The study was conducted from October-December of 2012 at St. Mary’s Mission Hospital, Lang’ata. HIV-positive birthmothers whose infants were HIV-negative at the time of the study were purposively selected to participate. All informants completed an interviewer-administered questionnaire (n = 55) and a subset (n = 15) participated in in-depth interviews. Contrary to the assertions of multiple studies that failures of PMTCT programs are a result of inadequate knowledge of mother-to-child transmission and PMTCT interventions, lack of support and acceptance by family and community, as well as poor quality of services, this study found these factors to be statistically insignificant in explaining PMTCT achievements. The study further found that HIV/AIDS related stigma and gender imbalances create many missed opportunities for HIV-positive mothers to apply acquired knowledge on mother-to-child transmission and PMTCT interventions, mobilize support from family and community, and access more affordable care. Factors found to influence women’s decisions to utilize and adhere to PMTCT services include supportive counseling, striving for motherhood, maternal attachment and concern for the child’s wellbeing, assurance of confidentiality and testimonials of other successful mothers. Based on the study findings, policy recommendations have been proposed along with suggestions for future research.

La transmission mère-enfant (TME) est un modèle naturel permettant d’explorer le rôle des anticorps neutralisants dans la protection vis-à-vis de l’infection par le VIH-1 ainsi que les caractéristiques des virus transmis aux enfants malgré la présence d’anticorps maternels. Au cours de mes travaux, nous avons confirmé l’importance de la région V2 de la glycoprotéine de surface (gp120) du VIH-1 dans la résistance du virus à la neutralisation. L’analyse des propriétés de variants transmis à l’enfant et de variants maternels a mis en évidence une grande hétérogénéité de leurs propriétés biologiques sans pour autant identifier de propriétés spécifiques conférant un avantage sélectif aux virus transmis. Cependant, nous avons montré que les virus transmis étaient plus sensibles à la neutralisation par deux anticorps monoclonaux humains largement neutralisants récemment identifiés, PG9 et PG16, une observation qui pourrait avoir des applications intéressantes en termes de prévention de la TME ou de développement vaccinal. Enfin, nous avons identifié deux résidus très conservés de la gp120 impliqués dans la sensibilité à la neutralisation par PG9 et/ou PG16. / Mother-to-child transmission (MTCT) provides a natural model for studying the role of neutralizing antibodies in preventing HIV-1 infection, and the characteristics of the virus transmitted to the infants despite the presence of maternal antibodies. During my thesis works, we confirmed that the V2 domain of the surface envelope glycoprotein (gp120) of HIV-1 plays a major role in resistance to neutralization. The analysis of properties of variants transmitted to infant and maternal variants showed a wide spectrum of their biological properties, but we did not identify any specific property conferring a selective advantage for transmission of the virus to the infant. Nevertheless, we showed that the transmitted variants were more sensitive to neutralization by the two recently described broadly neutralizing monoclonal antibodies PG9 and PG16. This observation should have interesting applications in terms of prevention of MTCT or vaccine development. Finally, we identified two gp120 cross-clade conserved residues involved in neutralization sensitivity to PG9 and/or PG16.

Ce travail a confirmé le rôle protecteur de certains anticorps neutralisants dans la TME du VIH-1, a permis de suggérer que certaines souches seraient de bons indicateurs d’anticorps neutralisants associés à la protection, et a confirmé le rôle de la région V2 de l’enveloppe virale en tant que cible des anticorps neutralisants. Les caractéristiques moléculaires des virus transmis dans le contexte de la TME confortent les données en faveur de la transmission à l’enfant d’une population virale restreinte génétiquement. Une gp 120 plus compacte et une moindre glycosylation ne sont pas des caractéristiques des virus transmis de la mère à l’enfant. Cependant, deux sites de N-glycosylation semblent être sélectionnés chez les virus transmis. L’identification de deux cas de TME liés à des variants issus de recombinaisons entre variants maternels a confirmé la présence d’un « hot spot » dans la région C2 du gène env, et a révélé pour la première fois un second « hot spot » dans la région C3. / A lower risk of MTCT was associated with higher NAb titers against the CRF01_AE strain, MBA, in Thailand. The results suggest that some primary isolates may be useful indicators for identifying protective antibodies, and confirm the role of the V2 region in neutralization. We found that only viruses of a restricted subset were transmitted to the infant. We did not find that shorter gp120 or fewer PNGS were characteristics of viruses transmitted from mother to infant. However, a limited number of PNGS, particularly at positions N301 and N384, may confer an advantage on the virus to be transmitted. Moreover, we identified two cases that suggest that recombination probably contributed to adaptation of HIV-1 to its environment to be successfully transmitted from mothers to their infants. In addition, our data allow both to confirm, in natural in vivo conditions, a hot spot for recombination in the C2 region of HIV-1 envelope gene, and to suggest another hot spot in the C3 region.