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The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p=0.045) and Nef (p=0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p<0.05) in Gag (n=10), Pol (n=7) and Nef (n=10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.

The COVID-19 pandemic disproportionately affected people from structurally vulnerable communities. There was a need to improve COVID-19 testing in these communities to reduce viral spread and connect to treatment. We created a partnership between an academic medical center and three community-based organizations (CBOs) to offer low-barrier COVID-19 walk-up testing clinics in Portland, Maine. Our objective was to examine whether the co-created testing clinics reached structurally vulnerable populations. The clinics offered COVID-19 rapid antigen tests three times a week outside CBO sites from January 2022 to May 2023. Clinic staff administered a brief survey on reason for testing and then instructed participants on how to self-swab. While staff processed the test, participants were invited to complete an additional survey about their demographics and testing perceptions. Adults seeking COVID-19 testing with specific outreach to people who are unhoused, immigrants, and low-income and/or uninsured. Number of tests conducted and result, reasons for testing, and testing perceptions. Of 246 completed tests, 18 were positive for COVID-19 (7%). Participants sought testing for a variety of reasons, including symptoms (60%), close contact exposure (29%), and/or need for a negative test result to access services or an activity (33%). Overall, people primarily tested due to symptoms with only 7% testing due to close contact exposure alone. The clinics reached vulnerable populations. Among the 130 people completing the participant survey, 39% were unhoused, 22% spoke a language other than English at home, 23% were uninsured, and 46% earned less than $20,000 in 2019. Qualitative field notes captured key elements of clinics that influenced reach, and how this collaboration with CBOs helped build trust with our target populations. Providing low-barrier walk-up clinics partnering with trusted CBOs was observed to be helpful in reaching structurally vulnerable populations for COVID-19 testing.

Children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA) parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC) pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN) and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery (PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value, and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa (control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was not significantly different between the two prophylactic regimens. Poisson regressions showed that LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75 (CI95%: 1.15–2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00–2.37), p = 0.05). Moreover, the proportion of children with MDD was unexpectedly high before randomisation in both groups. Long-term health impacts of these mitochondrial DNA parameters should be investigated further for both CHEU and HIV-infected children receiving LPV/r- or 3TC- based regimens.

Background The COVID-19 pandemic disproportionately affected people from structurally vulnerable communities. There was a need to improve COVID-19 testing in these communities to reduce viral spread and connect to treatment. Objective We created a partnership between an academic medical center and three community-based organizations (CBOs) to offer low-barrier COVID-19 walk-up testing clinics in Portland, Maine. Our objective was to examine whether the co-created testing clinics reached structurally vulnerable populations. Design The clinics offered COVID-19 rapid antigen tests three times a week outside CBO sites from January 2022 to May 2023. Clinic staff administered a brief survey on reason for testing and then instructed participants on how to self-swab. While staff processed the test, participants were invited to complete an additional survey about their demographics and testing perceptions. Participants Adults seeking COVID-19 testing with specific outreach to people who are unhoused, immigrants, and low-income and/or uninsured. Main Measures Number of tests conducted and result, reasons for testing, and testing perceptions. Key Results Of 246 completed tests, 18 were positive for COVID-19 (7%). Participants sought testing for a variety of reasons, including symptoms (60%), close contact exposure (29%), and/or need for a negative test result to access services or an activity (33%). Overall, people primarily tested due to symptoms with only 7% testing due to close contact exposure alone. The clinics reached vulnerable populations. Among the 130 people completing the participant survey, 39% were unhoused, 22% spoke a language other than English at home, 23% were uninsured, and 46% earned less than $20,000 in 2019. Qualitative field notes captured key elements of clinics that influenced reach, and how this collaboration with CBOs helped build trust with our target populations. Conclusions Providing low-barrier walk-up clinics partnering with trusted CBOs was observed to be helpful in reaching structurally vulnerable populations for COVID-19 testing.

Doc number: O60

This paper assesses the relative contribution of maternal, household, child, and poverty characteristics to the quality of the home environment. The sample consists of 1,887 children birth to 4 years old from the National Longitudinal Survey of Youth (NLSY). Ordinary least-squares regression is used to explore conceptually distinct aspects of children's poverty experiences. Poverty variables are found to have a statistically significant effect on the quality of the home environment, after controlling for the effects of other variables in the models. Statistically significant interactions among poverty variables are identified. A major finding is that improvements in family income have the strongest effects on the quality of the home environment for children who were born poor or lived much of their lives in poverty. The conclusion emphasizes implications for future research.

This study uses structural equation modeling to explore the determinants of the developmental status of young children. Data pertain to 1,742 children under the age of 48 months in the National Longitudinal Survey of Youth (NLSY). The literature reviewed suggests that characteristics of mother, household, and child collectively influence the quality of the home environment, which mediates the influence of demographic and socioeconomic variables on child outcomes. The study assesses this model on an experimental and a reserve sample for all children and for specific subgroups. Fit indices were satisfactory, and anticipated subgroup differences were not found.

Malnutrition contributes to more than one third of all child deaths, although hardly listed as the direct cause. In sub-Saharan Africa, malnutrition accounts for about 2% of deaths and 3% of Disability adjusted life years (DALYs) among under-5 children. In Zambia, 35% of under-5 children are stunted, 4% wasted, 12% underweight and 5% overweight. Malnutrition and HIV interact in complex ways that increase vulnerability to and worsen each condition therefore we sought to determine factors associated with malnutrition among under 5 children in Zambia. Using Stata version 14.2, we extracted and analysed sample data of 159 children aged 0-59 months from the 2016 ZAMPHIA population-based survey, that used a two-stage cluster sampling design. We used Generalised Linear Models to measure socio-economic factors associated with malnutrition. P-value of less than 0.05 was set as level of statistical significance. Factors associated with malnutrition included gender, child's HIV status and wealth index which showed an association with stunting, wasting and being underweight. The 16 (10%) under-5 children living with HIV were significantly more affected by stunting (38% vs 33%), wasting (19% vs 11%) and underweight prevalence (38% vs 10%) than the remaining 143 who were HIV negative. Our sample prevalence was similar to national stunting (33% vs 35%) and underweight prevalence (13% vs 12%) but had three times higher wasting prevalence (12% vs 4%). A high prevalence of malnutrition was found in HIV positive compared to negative under 5 children, wealth index showing an association with malnutrition. Eliminating malnutrition is key to attaining SDG 3 which is to end preventable deaths of newborns and children under 5 years of age.

STUDY OBJECTIVES: The main aim of the study was to discover if a midwife home visiting programme has a significant effect on the prevalence of health problems and breast feeding behaviour of mothers who delivered normally and their healthy fullterm newborn babies, during a period of 42 days after delivery. Another aim was to compare the mothers', the midwife's, and the doctor's findings of prevalence of health problems at the end of the puerperium period. DESIGN: A randomised controlled trial was carried out. One group of mothers and their infants were randomly allocated to a home visiting group (Group A); the other group (Group B) was only visited at day 42. SETTING: The study was carried out at the University Teaching Hospital (UTH) in Lusaka, the capital city of Zambia. PARTICIPANTS: A total of 408 mothers who had a normal delivery and gave birth to a healthy fullterm infant, as assessed by the attending midwife, were randomised to two groups. Group A consisted of 208 mother/infant dyads who were visited by a midwife in their homes at days 3, 7, 28, and 42 after delivery and Group B consisted of 200 mother/infant dyads who were only visited at day 42. MAIN RESULTS: At day 42 an equal proportion (30%) of mothers in both groups perceived that they had health problems. The prevalence of infant health problems in Group B was significantly higher (p < 0.01) as perceived by mothers. There were more mothers in Group B (p < 0.01) perceiving insufficient milk production and giving supplementary feeding. At day 42, mothers in Group A (56%) took more actions than mothers in Group B (41%) to solve infant health problems (p < 0.03). In both groups the mothers' perceived own health problems, were significantly higher (p < 0.01) than those observed by the obstetrician and those observed by the midwife. The midwife found more infant health problems in Group B (p < 0.01) than in Group A and more infants with health problems in both groups compared with the paediatrician's findings (p < 0.01). CONCLUSIONS: There was a significant difference between the mothers' reported health problems and the health problems identified by the midwife and the doctors. The study shows that a midwife home visit and individual health education to mothers, reduce the prevalence of infant health problems, and enables the mother to more often take action when an infant health problem is identified. There is a need to re-evaluate the midwifery training curriculums with the intention to include more infant management care.

STUDY OBJECTIVE--The aim was to investigate the relationship between duration of breast feeding and growth of children. DESIGN--The study was a survey of randomly selected clusters of households. SETTING--The study was community based and took place in an urban township with a population of over 43,000 people in Lusaka, the capital city of Zambia. PARTICIPANTS--The sample consisted of 438 children aged 0 to 59 months surveyed between October 1984 and June 1986. Due to missing information, 394 children were used in the analysis. MEASUREMENTS AND MAIN RESULTS--After controlling for confounding variables, duration of breast feeding was found to be associated with height for age among children in their first two years of life, but not in the later years of life. There was no significant protective effect of breast feeding on undernutrition and acute malnutrition as measured by weight for age and weight for height. CONCLUSIONS--The findings suggest that, in this community, duration of breast feeding is strongly associated with the linear growth experiences of children and the association changes with the infant's age. One strong risk factor suspected to be responsible for the poor growth performance of children in this study is the low nutritional quality of the weaning foods which are used to supplement breast milk during the lengthy weaning period.