HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant.

HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ∼1 year post-infection, including one with cross-clade breadth. The nAbs bind to envelope trimer from the transmitted virus, suggesting that this interaction may have initiated development of the infant nAbs. The infant cross-clade bnAb targets the N332 supersite on envelope but, unlike adult bnAbs targeting this site, lacks indels and has low SHM. The identification of this infant bnAb illustrates that HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM.

Risk factors of adverse birth outcomes among a cohort of pregnant women in Coastal Kenya, 2017-2019.

INTRODUCTION: Adverse birth outcomes particularly preterm births and congenital anomalies, are the leading causes of infant mortality globally, and the burden is highest in developing countries. We set out to determine the frequency of adverse birth outcomes and the risk factors associated with such outcomes in a cohort of pregnant women in Kenya. METHODS: From October 2017 to July 2019, pregnant women < 28 weeks gestation were enrolled and followed up until delivery in three hospitals in coastal Kenya. Newborns were examined at delivery. Among women with birth outcome data, we assessed the frequency of congenital anomalies defined as gastroschisis, umbilical hernia, limb abnormalities and Trisomy 21, and adverse birth outcomes, defined as either stillbirth, miscarriage, preterm birth, small for gestational age, or microcephaly. We used log-binomial regression to identify maternal characteristics associated with the presence of at least one adverse outcome. RESULTS: Among the 2312 women enrolled, 1916 (82.9%) had birth outcome data. Overall, 402/1916 (20.9%; 95% confidence interval (CI): 19.1-22.8) pregnancies had adverse birth outcomes. Specifically, 66/1916 (3.4%; 95% CI: 2.7-4.4) were stillbirths, 34/1916 (1.8%; 95% CI: 1.2-2.4) were miscarriages and 23/1816 (1.2%; 95% CI: 0.8-1.9) had congenital anomalies. Among the participants with anthropometric measurements data, 142/1200 (11.8%; 95% CI: 10.1 - 13.8) were small for gestational age and among the participants with ultrasound records, 143/1711 (8.4%; 95% CI: 7.1-9.8) were preterm. Febrile illnesses in current pregnancy (adjusted risk ratio (aRR): 1.7; 95% CI: 1.1-2.8), a history of poor birth outcomes in prior pregnancy (aRR: 1.8; 95% CI: 1.3-2.4) and high blood pressure in pregnancy (aRR: 3.9, 95% CI: (1.7-9.2) were independently associated with adverse birth outcomes in a model that included age, education, human immunodeficiency virus status and high blood pressure at enrolment. CONCLUSION: We found similar rates of overall adverse birth outcomes, congenital anomalies, and small for gestational age but higher rates of stillbirths and lower rates of prematurity compared to the rates that have been reported in the sub-Saharan Africa region. However, the rates of adverse birth outcomes in this study were comparable to other studies conducted in Kenya. Febrile illnesses during the current pregnancy, previous history of poor birth outcomes and high blood pressure in pregnancy are predictive of an increased risk of adverse birth outcomes.

Developing a global partnership to adapt and deliver interprofessional education faculty training in Kenya during the COVID-19 pandemic: reporting on an innovative collaboration.

Interprofessional (IP) education is imperative to foster collaboration within and between healthcare professions to improve healthcare delivery and outcomes. Increasing the capacity of health professions faculty to effectively deliver learning about IP knowledge and skills fosters sustainability of IP care in health systems. This short report describes a series of three virtual IP faculty development workshops during 2020-2021 that used a Train-the-Trainer approach and adopted flexible and context-specific teaching methods to enhance learning. The collaboration involved interprofessional researchers from the University of Washington Center for Health Sciences Interprofessional Education, Research, and Practice and Kenyan health professions faculty and was supported by a global health grant. Learners were drawn from multiple health professions and healthcare institutions in Kenya. Content was packaged in lectures, videos, pictures, and session notes. Teaching methods adopted included lecturing, discussing, playing videos, interpretation of pictures, and reading text notes. The Train-the-Trainer approach helped ensure that workshop content and plans were relevant to participants. Workshop participants shared positive feedback about the trainings and showed a good grasp of the concepts and skills. In-built feedback mechanisms in training were key in supporting the programme and ensured continuous improvement within and between sessions. This collaboration offers an innovative example of a global partnership to support IP faculty development and mainstreaming of IPE in training and in practice.

Association between low maternal serum aflatoxin B1 exposure and adverse pregnancy outcomes in Mombasa, Kenya, 2017-2019: A nested matched case-control study.

We examined the association between serum aflatoxin B1-lysine adduct (AFB1-lys) levels in pregnant women and adverse pregnancy outcomes (low birthweight, miscarriage and stillbirth) through a nested matched case-control study of pregnant women enroled at ≤28 weeks' gestation in Mombasa, Kenya, from 2017 to 2019. Cases comprised women with an adverse birth outcome, defined as either delivery of a singleton infant weighing <2500 g, or a miscarriage, or a stillbirth, while controls were women who delivered a singleton live infant with a birthweight of ≥2500 g. Cases were matched to controls at a ratio of 1:2 based on maternal age at enrolment, gestational age at enrolment and study site. The primary exposure was serum AFB1-lys. The study included 125 cases and 250 controls. The median gestation age when serum samples were collected was 23.0 weeks (interquartile range [IQR]: 18.1-26.0) and 23.5 (IQR: 18.1-26.5) among cases and controls, respectively. Of the 375 tested sera, 145 (38.7%) had detectable serum AFB1-lys: 36.0% in cases and 40.0% in controls. AFB1-lys adduct levels were not associated with adverse birth outcomes on multivariable analysis. Mid-upper arm circumference was associated with a 6% lower odds of adverse birth outcome for every unit increase (p = 0.023). Two-fifths of pregnant women had detectable levels of aflatoxin midway through pregnancy. However, we did not detect an association with adverse pregnancy outcomes, likely because of low serum AFB1-lys levels and low power, restricting meaningful comparison. More research is needed to understand the public health risk of aflatoxin in pregnant women to unborn children.

Understanding sexual behaviors of youth from the lens of caregivers, teachers, local leaders and youth in Homabay County, Kenya.

In Kenya similar to other countries in Eastern and Southern Africa There is a disproportionately high burden of the global HIV incidence among youth ages 15-24 years, and where adolescent girls and young women account for up to a third of all incident HIV infections and more than double the burden of HIV compared to their male peers. Previous work has shown early sexual debut as entry point into risks to sexual and reproductive health among young people including STI/HIV acquisition. This was a formative assessment of the local context of three sexual risk behaviors among youth ages of 15-24 years: early sexual debut, multiple sexual partnerships, and age-mixing /intergenerational sex for purposes of informing comprehensive combination HIV intervention program design. We conducted a cross-sectional formative qualitative study in four sub-counties within Homabay county a high HIV prevalence region of Kenya. Participants were recruited through youth groups, schools, government offices and, community gatekeepers using approved fliers, referred to a designated venue for focus group discussion (FGD). After oral informed consent, twelve FGDs of 8-10 participants were carried out. Transcripts and field notes were uploaded to Atlas.ti qualitative data analysis and research software (version 8.0, 2017, ATLAS.ti GmbH). Open coding followed by grouping, categorization of code groups, and thematic abstraction was used to draw meaning for the data. A total of 111 youth participated in the FGD, 65 males and 46 females. The main findings were that youth engaged in early sex for fear of being labeled 'odd' by their peers, belief (among both male and female) that 'practice makes perfect', curiosity about sex, media influence, need to prove if one can father a child (among male), the notion that sex equals love with some of the youth using this excuse to coerce their partners into premature sex, and the belief that sex is a human right and parents/guardians should not intervene. Male youth experienced more peer-pressure to have sex earlier. Female youths cited many reasons to delay coitarche that included fear of pregnancy, burden of taking care of a baby, and religious doctrines. Having multiple sexual partners and intergenerational sexual relationships were common among the youth driven by perceived financial gain and increased sexual prowess. HIV prevention strategies need to address gender vulnerabilities, as well as promoting a protective environment, hence application of combination prevention methods is a viable solution to the HIV pandemic.Trial registration number: The study was approved by the KNH/UoN Ethics review committee (KNH/UoN ERC-P73/03/2011) and New York University (NYU Reg no.-00000310).

Perinatal care and breastfeeding education during the COVID-19 pandemic: Perspectives from Kenyan mothers and healthcare workers.

The impact of the COVID-19 pandemic on breastfeeding (BF) practices in low- and middle-income countries (LMICs) is not well understood. Modifications in BF guidelines and delivery platforms for breastfeeding education during the COVID-19 pandemic are hypothesised to have affected BF practices. We aimed to understand the experiences with perinatal care, BF education and practice among Kenyan mothers who delivered infants during the COVID-19 pandemic. We conducted in-depth key informant interviews with 45 mothers who delivered infants between March 2020 and December 2021, and 26 health care workers (HCW) from four health facilities in Naivasha, Kenya. While mothers noted that HCWs provided quality care and BF counselling, individual BF counselling was cited to be less frequent than before the pandemic due to altered conditions in health facilities and COVID-19 safety protocols. Mothers stated that some HCW messages emphasised the immunologic importance of BF. However, knowledge among mothers about the safety of BF in the context of COVID-19 was limited, with few participants reporting specific counselling or educational materials on topics such as COVID-19 transmission through human milk and the safety of nursing during a COVID-19 infection. Mothers described COVID-19-related income loss and lack of support from family and friends as the major challenge to practising exclusive breastfeeding (EBF) as they wished or planned. COVID-19 restrictions limited or prevented mothers' access to familial support at facilities and at home, causing them stress and fatigue. In some cases, mothers reported job loss, time spent seeking new means of employment and food insecurity as causes for milk insufficiency, which contributed to mixed feeding before 6 months. The COVID-19 pandemic created changes to the perinatal experience for mothers. While messages about the importance of practising EBF were provided, altered HCW education delivery methods, reduced social support and food insecurity limit EBF practices for mothers in this context.

Comparable Pregnancy Outcomes for HIV-Uninfected and HIV-Infected Women on Antiretroviral Treatment in Kenya.

BACKGROUND: The impact of human immunodeficiency virus (HIV) on pregnancy outcomes for women on antiretroviral therapy (ART) in sub-Saharan Africa remains unclear. METHODS: Pregnant women in Kenya were enrolled in the second trimester and followed up to delivery. We estimated effects of treated HIV with 3 pregnancy outcomes: loss, premature birth, and low birth weight and factors associated with HIV-positive status. RESULTS: Of 2113 participants, 311 (15%) were HIV infected and on ART. Ninety-one of 1762 (5%) experienced a pregnancy loss, 169/1725 (10%) a premature birth (<37 weeks), and 74/1317 (6%) had a low-birth-weight newborn (<2500 g). There was no evidence of associations between treated HIV infection and pregnancy loss (adjusted relative risk [aRR], 1.19; 95% confidence interval [CI], .65-2.16; P = .57), prematurity (aRR, 1.09; 95% CI, .70-1.70; P = .69), and low birth weight (aRR, 1.36; 95% CI, .77-2.40; P = .27). Factors associated with an HIV-positive status included older age, food insecurity, lower education level, higher parity, lower gestation at first antenatal clinic, anemia, and syphilis. Women who were overweight or underweight were less likely to be HIV infected compared to those with normal weight. CONCLUSIONS: Currently treated HIV was not significantly associated with adverse pregnancy outcomes. HIV-infected women, however, had a higher prevalence of other factors associated with adverse pregnancy outcomes.

Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017-2019.

BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT90) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.

Developing an Unstructured Supplementary Service Data-based mobile phone app to provide adolescents with sexual reproductive health information: a human-centered design approach.

BACKGROUND: Adolescent pregnancies and sexually-transmitted infections continue to impact 15 - 19-year-olds across the globe. The lack of sexual reproductive health information (SRH) in resource-limited settings due to cultural and societal attitudes towards adolescent SRH could be contributing to the negative outcomes. Innovative approaches, including mobile phone technologies, are needed to address the need for reliable adolescent SRH information. OBJECTIVE: The study aimed to co-design a Unstructured Supplementary Service Data (USSD) based mobile app prototype to provide confidential adolescent SRH information on-demand and evaluate the mobile app's usability and user experience. METHODS: A human-centered design methodology was applied. This practice framework allowed the perspectives and feedback of adolescent users to be included in the iterative design process. To participate, an adolescent must have been 15 to 19 years old, resided in Kibra and would be able to access a mobile phone. Adolescents were enrolled for the alpha and field testing of the app prototype at different time-points. The Mobile Application Rating Scale (MARS) a multidimensional mobile phone evaluation tool was used to access the functionality, engagement, aesthetics and quality of information in the app. Responses from the MARS were reported as mean scores for each category and a mean of the aggregate scores making the app's quality score. The MARS data was also evaluated as categorical data, A Chi square test of independence was carried out to show significance of any observed differences using cumulative and inverse cumulative distribution functions. RESULTS: During the usability test, 62/109 (54.9%) of the adolescents that were followed-up had used the app at least once, 30/62 (48.4%) of these were male participants and 32/62 (51.6%) female. On engagement, the app had a mean score of 4.3/5 (SD 0.44), 4.6/5 (SD 0.38) on functionality, 4.3/5 (SD 0.57) on aesthetics and 4.4/5 (SD 0.60) on the quality of information. The overall app quality mean score was 4.4/5 (SD 0.31). The app was described as 'very interesting' to use by 44/62 (70.9%) of the participants, 20/44 males and 24/44 females. The content was deemed to be either 'perfectly' or 'well targeted' on sexual reproductive health by 60/62 (96.7%) adolescents, and the app was rated 'best app' by 45/62 (72.6%) adolescents, 27/45 females and 18/45 males, with a p-value = 0.011. CONCLUSIONS: Adolescents need on-demand, accurate and trusted SRH information. A mobile phone app is a feasible and acceptable way to deliver adolescent SRH information in resource-limited settings. The USSD mobile phone technology shows promise in the delivery of much needed adolescent SRH information on-demand..

Diversity and Function of Maternal HIV-1-Specific Antibodies at the Time of Vertical Transmission.

Infants of HIV-positive mothers can acquire HIV infection by various routes, but even in the absence of antiviral treatment, the majority of these infants do not become infected. There is evidence that maternal antibodies provide some protection from infection, but gestational maternal antibodies have not yet been characterized in detail. One of the most studied vertically infected infants is BG505, as the virus from this infant yielded an Envelope protein that was successfully developed as a stable trimer. Here, we isolated and characterized 39 HIV-specific neutralizing monoclonal antibodies (nAbs) from MG505, the mother of BG505, at a time point just prior to vertical transmission. These nAbs belonged to 21 clonal families and employed a variety of VH genes. Many were specific for the HIV-1 Env V3 loop, and this V3 specificity correlated with measurable antibody-dependent cellular cytotoxicity (ADCC) activity. The isolated nAbs did not recapitulate the full breadth of heterologous or autologous virus neutralization by contemporaneous plasma. Notably, we found that the V3-targeting nAb families neutralized one particular maternal Env variant, even though all tested variants had low V3 sequence diversity and were measurably bound by these nAbs. None of the nAbs neutralized BG505 transmitted virus. Furthermore, the MG505 nAb families were found at relatively low frequencies within the maternal B cell repertoire; all were less than 0.25% of total IgG sequences. Our findings illustrate an example of the diversity of HIV-1 nAbs within one mother, cumulatively resulting in a collection of antibody specificities that can contribute to the transmission bottleneck.IMPORTANCE Mother-to-child-transmission of HIV-1 offers a unique setting in which maternal antibodies both within the mother and passively transferred to the infant are present at the time of viral exposure. Untreated HIV-exposed human infants are infected at a rate of 30 to 40%, meaning that some infants do not get infected despite continued exposure to virus. Since the potential of HIV-specific immune responses to provide protection against HIV is a central goal of HIV vaccine design, understanding the nature of maternal antibodies may provide insights into immune mechanisms of protection. In this study, we isolated and characterized HIV-specific antibodies from the mother of an infant whose transmitted virus has been well studied.

Efficacy of Mobile phone use on adherence to Nevirapine prophylaxis and retention in care among the HIV-exposed infants in prevention of mother to child transmission of HIV: a randomized controlled trial.

BACKGROUND: HIV is a major contributor to infant mortality. A significant gap remains between the uptake of infant and maternal antiretroviral regimens and only a minority of HIV-exposed infants receives prophylaxis and safe infant feeding. Losses to follow-up of HIV-exposed infants are associated with shortcomings of facility-based PMTCT models with weak community support of linkages. Use of mobile phones offers an opportunity for improving care and promoting retention assessed by timely attendance of scheduled appointments for the mother-baby pairs and achievement of an HIV-free generation. The objective of this study was to compare self-reported adherence to infant Nevirapine (NVP) prophylaxis and retention in care assessed by timely attendance of scheduled appointments over 10 weeks in HIV exposed infants randomized to 2-weekly mobile phone calls (intervention) versus no phone calls (control). METHODS: In this open label randomized controlled study, one hundred and fifty HIV infected women drawn from 3 health facilities in Western Kenya and their infants were randomly assigned to receive either phone-based reminders on PMTCT messages or standard health care messages (no calls) within 24 h of delivery. Women in the intervention arm continued to receive fortnightly phone calls. At 6- and 10-weeks following randomization we collected data on infant adherence to Nevirapine, mode of infant feeding, early HIV testing and retention in care in both study arms. All analyses were intention to treat. RESULTS: At 6 weeks follow-up, 90.7% (n = 68) of participants receiving phone calls reported adherence to infant NVP prophylaxis, compared with 72% (n = 54) of participants in the control group (p = 0.005). Participants in the intervention arm were also significantly more likely to remain in care than participants in the control group [78.7% (n = 59) vs. 58.7% (n = 44), p = 0.009 at 6 weeks and 69.3% (n = 52) vs. 37.3% (n = 28), p < 0.001 at 10 weeks]. CONCLUSIONS: These results suggest that phone calls are potentially an important tool to improve adherence to infant NVP prophylaxis and retention in care for HIV-exposed infants. TRIAL REGISTRATION: PACTR202007654729602. Registered 6 June 2018 - Retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3449.

Exclusive breastfeeding among working mothers in Kenya: Perspectives from women, families and employers.

Exclusive breastfeeding (EBF) for the first 6 months of life improves survival, growth and development. In Kenya, recent legislation and policies advocate for maternity leave and workplace support for breastfeeding and breast milk expression. We conducted a qualitative study to describe factors influencing EBF for 6 months among mothers employed in commercial agriculture and tourism. We interviewed employed mothers (n = 42), alternate caregivers and employed mothers' husbands (n = 20), healthcare providers (n = 21), daycare directors (n = 22) and commercial flower farm and hotel managers (n = 16) in Naivasha, Kenya. Despite recognizing the recommended duration for EBF, employed mothers describe the early cessation of EBF in preparation for their return to work. Managers reported supporting mothers through flexible work hours and duties. Yet, few workplaces have lactation spaces, and most considered adjusting schedules more feasible than breastfeeding during work. Managers and healthcare providers believed milk expression could prolong EBF but thought mothers lack experience with pumping. The most frequently suggested interventions for improving EBF duration were to expand schedule flexibility (100% of groups), provide on-site daycare (80% of groups) and workplace lactation rooms (60% of groups), improve milk expression education and increase maternity leave length (60% of groups). Returning to work corresponds with numerous challenges including lack of proximate or on-site childcare and low support for and experience with milk expression. These factors currently make EBF for 6 months unattainable for most mothers in these industries. Interventions and supports to improve breastfeeding upon return to work are recommended to strengthen employed mothers' opportunity for EBF.

Maternal Envelope gp41 Ectodomain-Specific Antibodies Are Associated With Increased Mother-to-Child Transmission of Human Immunodeficiency Virus-1.

Mother-to-child transmission of human immunodeficiency virus (HIV) occurs in the setting of maternal and passively acquired antibodies, providing a unique window into immune correlates of HIV risk. We compared plasma antibody binding to HIV antigens between 51 nontransmitting mother-infant pairs and 21 transmitting mother-infant pairs. Plasma antibody binding to a variety of gp41 ectodomain-containing antigens was associated with increased odds of transmission. Understanding the reasons why gp41 ectodomain-targeting antibodies are associated with transmission risk will be important in determining whether they can directly enhance infection or whether their presence reflects a redirecting of the humoral response away from targeting more protective epitopes.

Making Smarter Decisions Faster: Systems Engineering to Improve the Global Public Health Response to HIV.

PURPOSE OF REVIEW: This review offers an operational definition of systems engineering (SE) as applied to public health, reviews applications of SE in the field of HIV, and identifies opportunities and challenges of broader application of SE in global health. RECENT FINDINGS: SE involves the deliberate sequencing of three steps: diagnosing a problem, evaluating options using modeling or optimization, and providing actionable recommendations. SE includes diverse tools (from process improvement to mathematical modeling) applied to decisions at various levels (from local staffing decisions to planning national-level roll-out of new interventions). Contextual factors are crucial to effective decision-making, but there are gaps in understanding global decision-making processes. Integrating SE into pre-service training and translating SE tools to be more accessible could increase utilization of SE approaches in global health. SE is a promising, but under-recognized approach to improve public health response to HIV globally.

Understanding mental health difficulties and associated psychosocial outcomes in adolescents in the HIV clinic at Kenyatta National Hospital, Kenya.

BACKGROUND: Globally adolescents continue to have an upward trend in HIV incidence and AIDS-related mortality. The interplay between the rapid physical growth, sexual maturation, and enormous albeit slow-evolving cognitive and psychological changes in adolescence may partly explain this trend. Our main purpose was to highlight key psychosocial characteristics of HIV-infected adolescents and explore if these characteristics are associated with depression symptoms. METHODS: From August to December 2016 after obtaining informed consent, adolescents living with HIV at Kenyatta National Hospital were interviewed using the Home environment, Education and Employment, Activity, Sexuality, Suicide and depression traits (HEADSS) tool combined with the Patient Health Questionnaire (PHQ-9) to elucidate which key symptoms of depression and link with psychosocial characteristics mapped on HEADSS. In order to determine which psychosocial characteristics were linked with risk of depression, the traits of adolescents who were symptomatic were compared to those who were not using univariate and multivariate regression analysis. RESULTS: All the 270 adolescents offered participation in the study accepted to enroll. The aged 10-19 years were recruited and mean age was 14.75 and 53.7% (n = 145) were males. Overall, 269 (99.9%) were still in school and 52.6% of the adolescents had symptoms of depression. The independent predictors of depression were being of ages 15-19 years [OR = 2.34 (95% CI 1.36, 4.04) P < 0.02], ever repeating classes [OR = 1.74 (95% CI 1.0-3.05) P = 0.05], ever being sent away from school due to lack of school fees [OR = 1.71 (95% CI 1.0-2.91) P = 0.05], and non-adherence to medication [OR = 1.84 (95% CI 1.08-3.14) P = 0.03. Missing of meals due to food insecurity was associated with an important trend towards increased risk of depression [OR = 2.42 (CI 0.96-6.14) P = 0.06]. CONCLUSION: One in two of the adolescents interviewed had depression symptoms which were significantly associated with lack of school fees, missing meals, non-adherence to medication, and substance abuse.

Vertical Cytomegalovirus Transmission From HIV-Infected Women Randomized to Formula-Feed or Breastfeed Their Infants.

BACKGROUND: Cytomegalovirus (CMV) is associated with morbidity and mortality in human immunodeficiency virus (HIV)-exposed infants. We assessed the effect of and relative contribution of breastfeeding to CMV acquisition among infants delivered by HIV-infected mothers. METHODS: Between 1993 and 1998 pregnant, HIV-infected women in Nairobi, Kenya, were randomly assigned to breastfeed or formula-feed their infants in an HIV transmission study. Women were allocated equally between treatment arms, and the study was not blinded. The primary endpoint of this nested study was time to infant CMV infection. RESULTS: CMV infection was assessed in 138 breastfed and 134 formula-fed infants. Baseline characteristics were similar between arms. Breastfed infants acquired CMV earlier than formula-fed infants (median age of acquisition, 4.26 vs 9.87 months; P < .001) and had a higher 1-year probability of CMV infection (0.89 vs 0.69; P < .001). Breastfeeding was associated with a 1.6-fold increased risk of infant CMV acquisition independent of infant HIV status (multivariable hazard ratio, 1.61; 95% confidence interval, 1.20-2.16; P = .002). Approximately one third of CMV infections occurred during the peripartum period, with 40% acquired through breastfeeding and the remainder acquired through modes other than breast milk. CONCLUSIONS: Preventing CMV acquisition may be a priority for HIV-exposed infants, but there is a narrow window of opportunity for intervention. Approaches that reduce maternal cervical and breast milk CMV reactivation may help delay infant infection.

Impact of highly active antiretroviral therapy on hematological indices among HIV-1 infected children at Kenyatta National Hospital-Kenya: retrospective study.

BACKGROUND: HIV infected children experience a range of hematological complications which show marked improvement within 6 months of initiating anti-retroviral therapy. The Objectives of the study was to describe the changes in hematological indices of HIV-1 infected children following 6 months of treatment with first line antiretroviral drugs (ARVs) regimen. METHODS: A retrospective study was conducted between September and November 2008. During this period medical records of children attending Comprehensive Care Clinic at Kenyatta National hospital were reviewed daily. HIV infected children aged 5-144 months were enrolled if they had received antiretroviral drugs for at least 6 months with available and complete laboratory results. RESULTS: Medical records of 337 children meeting enrollment criteria were included in the study. The median age was 63 months with equal male to female ratio. Following 6 months of HAART, prevalence of anemia (Hemoglobin (Hb) <10 g/dl) declined significantly from 35.9 to 16.6 % a nearly 50 % reduction in the risk of anemia RR = 0.56 [(95 % CI 0.44, 0.70) p < 0.001]. There was significant increase in Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and platelets above the baseline measurements (p < 0.0001) and a significant decline in total white blood cell counts >11,000 cell/mm(3) but a none significant decrease in red blood cells (RBC). Pre-HAART, World Health Organization (WHO) stage 3 and 4 was associated with a ten-fold increased likelihood of anemia. Chronic malnutrition was associated with anemia but not wasting and immunologic staging of disease. CONCLUSION: Hematological abnormalities changed significantly within 6 months of antiretroviral therapy with significant increase in hemoglobin level, MCV, MCH and platelet and decrease in WBC and RBC.

The Gender Context of HIV Risk and Pregnancy Goals in Western Kenya.

BACKGROUND: Intentional childbearing may place heterosexual couples at risk of HIV infection in resource-limited settings with high HIV prevalence areas where society places great value on having children. OBJECTIVE: To explore cognitive, cultural, and spatial mapping of sexual and reproductive health domains and services in western Kenya among men and women. DESIGN: Community-based formative qualitative study design. SETTING: Five administrative/geographical divisions of Nyando District, western Kenya. SUBJECTS: Adult men 18 years and older and women who were of reproductive-potential ages (15 to 49 years for females) (n=90). RESULTS: Men and women have disparate goals for number of children and engage in gendered patterns of protective method use (contraceptives used by women often in secret, condoms by men but rarely). CONCLUSION: HIV infection was still seen as stigmatizing. These study results are relevant to design of effective integrated delivery for reproductive and HIV services in high-burden sub-Saharan African countries.

HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.

There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS)--only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log(10) lower (compared to 0.59 log(10) lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001) and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk.