Predictors of loss to follow-up among children attending HIV clinic in a hospital in rural Kenya.

INTRODUCTION: African studies have reported high rates of loss to follow up (LTFU) among children in HIV care and treatment centres. Factors associated with LTFU may vary across populations. Few studies have been conducted among HIV infected children in care in rural areas of Kenya. METHODS: this involved children aged less than 15 years on follow up at Kangundo Level 4 Hospital HIV clinic from January 2010 to December 2015. We obtained sociodemographic and clinical information from patient files and electronic databases. Univariate and multivariate regression analyses were conducted to identify factors predictive of LTFU. RESULTS: a total of 261 HIV-infected children were followed up. The mean age was 10.0 years (IQR, 7-13) and median CD4 count of 582cells/ul (IQR 314-984). By December 2015, 171 children (65.5%) remained in active care, 32 (12.3%) transferred out, 13 (5%) died, while 45 (17.2%) were classified as LTFU. Out of the 45 children presumed as LTFU, we traced 44 out of the 45 children (98%) and found that their actual current status was as follows: 33 of the 44 children (75.0%) had dropped out of care (true LTFU). Factors strongly predictive of LTFU included low caregiver level of education (HR 2.3, 1.9-3.9, P = 0.001), WHO stage I and II at enrolment (HR 1.6, 1.4-2.1, P = 0.05). CONCLUSION: LTFU of HIV infected children was common with an incidence of 32.9 per 1000 child years and occurred early in treatment and risk factors included poverty, low caregiver education, male child and early HIV disease stage.

Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV-Exposed, Uninfected Kenyan Infants.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa, with higher morbidity and mortality than HIV-unexposed infants. HEU infants may experience increased morbidity due to breastfeeding avoidance. OBJECTIVES: We sought to describe the burden and identify predictors of hospitalization among HEU infants in the first year of life. METHODS: Using a retrospective cohort of HIV-infected mothers and their HEU infants in Nairobi, Kenya, we identified infants who were HIV-uninfected at birth and were followed monthly until their last negative HIV test, death, loss to follow-up, or study exit at 1 year of age. Incidence, timing, and reason for hospitalization was assessed overall as well as stratified by feeding method. Predictors of first infectious disease hospitalization were identified using competing risk regression, with HIV acquisition and death as competing risks. RESULTS: Among 388 infants, 113 hospitalizations were reported (35/100 infant-years [the combined years of observation contributed by all infants in the study]; 95% confidence interval [CI], 29-42). Ninety hospitalizations were due to 1 or more infectious diseases (26/100 infant-years; 95% CI, 21-32)-primarily pneumonia (n = 40), gastroenteritis (n = 17), and sepsis (n = 14). Breastfeeding was associated with decreased risk of infectious disease hospitalization (subhazard ratio = 0.39; 95% CI, 0.24-0.64), as was time-updated nutrition status (subhazard ratio = 0.73; 95% CI, 0.61-0.89). Incidence of infectious disease hospitalization among formula-fed infants was 51/100 infant-years (95% CI, 37-70) compared to 19/100 infant-years (95% CI, 14-25) among breastfed infants. CONCLUSION: Among HEU infants, breastfeeding and nutrition status were associated with reduced hospitalization during the first year of life.

PedVacc 002: a phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi.

BACKGROUND: A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants. TRIAL DESIGN: A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya. METHODS: Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines. RESULTS: Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p=0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p=0.05). CONCLUSIONS: This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens.

Infant Neutropenia Associated with Breastfeeding During Maternal Antiretroviral Treatment for Prevention of Mother-to-Child Transmission of HIV.

Maternal antiretroviral treatment (ART) is recommended for prevention of mother-to-child HIV-1 transmission (PMTCT), including in women with high CD4+ cell counts. Within a pediatric HIV-1 vaccine trial PedVacc 002, we assessed hematologic profiles of infants born to mothers receiving ART. All mothers had CD4+ cell counts of >350 mm-3; 93% received zidovudine-containing ART; infants received nevirapine up to 6 weeks and cotrimoxazole after 6 weeks. Among 84 infants at 19 weeks, 58% had hematologic toxicity; 44% had neutropenia and 23% had anemia. Breastfeeding was associated with 3.8-fold higher risk of neutropenia (RR 3.8, 95% CI 1.03-14.1, p = 0.008). Hematologic monitoring and PMTCT regimen selection are important for optimizing infant outcomes.

Infant feeding modes and determinants among HIV-1-infected African Women in the Kesho Bora Study.

OBJECTIVE: To assess breastfeeding modes and determinants in a prevention of mother-to-child transmission study. DESIGN: HIV-1-infected pregnant women from 5 sites in Burkina Faso, Kenya, and South Africa were enrolled in the study that comprised 2 prospective cohorts and 1 randomized controlled trial. Women were counseled to either breastfeed exclusively up to 6 months or formula feed from birth. METHODS: Determinants of breastfeeding initiation and continuation by 3 months postpartum were investigated using multiple logistic regression analysis. Neonatal morbidity was defined as mother-reported fever, diarrhea, or vomiting during the first month of life. RESULTS: Among 1028, 781 women (76%) initiated breastfeeding and 565 of 995 (56%) were still breastfeeding at 3 months postpartum (30% exclusively, 18% predominantly, and 8% partially). Study site (Durban, Mombasa, and Nairobi compared with Bobo-Dioulasso), CD4 cell count (<200 cells/mm), secondary schooling (compared with none), and emergency cesarean delivery (compared with vaginal delivery) were independently associated with a lower probability of ever breastfeeding. The odds of still breastfeeding by 3 months postpartum (among those breastfeeding by 1 month) were lower in Mombasa, Nairobi, and Somkhele (compared with Bobo-Dioulasso) and among infants with neonatal morbidity [0.60 (0.37-0.976)]. The odds of exclusive breastfeeding (EBF) by 3 months (if EBF by 1 month) were lower in Mombasa and Nairobi, in ill neonates [0.54 (0.31-0.93)] and boys [0.51 (0.34-0.77)]. CONCLUSIONS: EBF was of short duration, particularly for boys. The importance of neonatal morbidity for breastfeeding cessation requires further investigation. Infant feeding counseling might need adaptation to better support mothers of boys and ill neonates.

Performance of the integrated management of childhood illness algorithm for diagnosis of HIV-1 infection among African infants.

OBJECTIVES: Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, integrated management of childhood illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants. METHODS: From 1999 to 2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis. RESULTS: Overall IMCI sensitivity, specificity, PPV, and NPV value were 58, 87, 52, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV infections already had occurred. Sensitivity increased with age (P < 0.0001), but remained low throughout infancy (range 1.4-35%). Specificity (range 97-100%) was high at each time point and was not associated with age. Fifty-eight percent of HIV-1-infected infants (50 of 86) were eventually diagnosed by IMCI, and use of IMCI was estimated to delay diagnosis in HIV-infected infants by a median of 5.9 months (P < 0.0001). CONCLUSION: IMCI had low sensitivity during the first month of life, when the majority of HIV-1 infections had already occurred and initiation of treatment is most critical. Although sensitivity increased with age, the substantial delay in HIV-1 diagnosis using IMCI limits its utility in early infant HIV-1 diagnosis.

Risk factors for neonatal conjunctivitis in babies of HIV-1 infected mothers.

PURPOSE: To determine the prevalence and correlates of neonatal conjunctivitis in infants born to human immunodeficiency virus type 1 (HIV-1) infected mothers. METHODS: This was a nested case-control study within a perinatal HIV-1 cohort. HIV-1 seropositive mothers were enrolled during pregnancy and mother-infant pairs followed after delivery with assessment for neonatal conjunctivitis at 48 hours and up to 4 weeks after birth. Genital infections (chlamydia, gonorrhea, syphilis, trichomonas, bacterial vaginosis, and candida) were screened for at 32 weeks gestation. Mothers received treatment for genital infections diagnosed during pregnancy and short-course zidovudine. Newborns did not receive ocular prophylaxis at hospital deliveries. Multivariate logistic regression models were used to determine cofactors for neonatal conjunctivitis overall and stratified for infant HIV-1 status. RESULTS: Four hundred and fifty-two infants were assessed and 101 (22.3%) had neonatal conjunctivitis during the first month postpartum. In multivariate analyses using odds ratios (OR) and confidence intervals (CI), neonatal conjunctivitis was associated with neonatal sepsis (adjusted OR 21.95, 95% CI 1.76, 274.61), birth before arrival to hospital (adjusted OR 13.91, 95% CI 1.39, 138.78) and birth weight (median 3.4 versus 3.3 kilograms, p=0.016, OR 1.79, 95% CI 1.01, 3.15). Infant HIV-1 infection was not associated with conjunctivitis. CONCLUSIONS: Despite detection and treatment of genital infections during pregnancy, neonatal conjunctivitis was frequently diagnosed in infants born to HIV-1 infected mothers suggesting a need for increased vigilance and prophylaxis for conjunctivitis in these infants. Neonatal sepsis, birth before arrival to hospital, and higher birthweight are factors that may predict higher risk of neonatal conjunctivitis in this population.

Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission.

Alpha-defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of alpha-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined < 48 h after birth and at months 1, 3, 6, 9, and 12. Breast milk specimens collected at month 1 were assayed for alpha-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected alpha-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable alpha-defensins (> or =50 pg/ml) had a median concentration of 320 pg/ml and significantly higher mean breast milk HIV-1 RNA levels than women with undetectable alpha-defensins (2.9 log(10) copies/ml versus 2.5 log(10) copies/ml, p = 0.003). Increased alpha-defensins concentrations in breast milk were also associated with subclinical mastitis (Na (+)/K(+) ratio > 1) and increased breast milk chemokine levels. Overall, 40 (15%) infants were HIV-1 uninfected at birth and subsequently acquired HIV-1. There was no significant association between month 1 alpha-defensins and risk of HIV-1 transmission. In conclusion, alpha-defensins were associated with breast milk HIV-1 viral load, chemokine levels, and subclinical mastitis, all of which may alter risk of infant HIV-1 acquisition. Despite these associations there was no significant relationship between breast milk alpha-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.

Early response to highly active antiretroviral therapy in HIV-1-infected Kenyan children.

OBJECTIVES: To describe the early response to World Health Organization (WHO)-recommended nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line highly active antiretroviral therapy (HAART) in HIV-1-infected Kenyan children unexposed to nevirapine. DESIGN: Observational prospective cohort. METHODS: HIV-1 RNA level, CD4 lymphocyte count, weight for age z score, and height for age z score were measured before the initiation of HAART and every 3 to 6 months thereafter. Children received no nutritional supplements. RESULTS: Sixty-seven HIV-1-infected children were followed for a median of 9 months between August 2004 and November 2005. Forty-seven (70%) used zidovudine, lamivudine (3TC), and an NNRTI (nevirapine or efavirenz), whereas 25% used stavudine (d4T), 3TC, and an NNRTI. Nevirapine was used as the NNRTI by 46 (69%) children, and individual antiretroviral drug formulations were used by 63 (94%), with only 4 (6%) using a fixed-dose combination of d4T, 3TC, and nevirapine (Triomune; Cipla, Mumbai, India). In 52 children, the median height for age z score and weight for age z score rose from -2.54 to -2.17 (P<0.001) and from -2.30 to -1.67 (P=0.001), respectively, after 6 months of HAART. Hospitalization rates were significantly reduced after 6 months of HAART (17% vs. 58%; P<0.001). The median absolute CD4 count increased from 326 to 536 cells/microL (P<0.001), the median CD4 lymphocyte percentage rose from 5.8% before treatment to 15.4% (P<0.001), and the median viral load fell from 5.9 to 2.2 log10 copies/mL after 6 months of HAART (P<0.001). Among 43 infants, 47% and 67% achieved viral suppression to less than 100 copies/mL and 400 copies/mL, respectively, after 6 months of HAART. CONCLUSION: Good early clinical and virologic response to NNRTI-based HAART was observed in HIV-1-infected Kenyan children with advanced HIV-1 disease.

High uptake of postpartum hormonal contraception among HIV-1-seropositive women in Kenya.

OBJECTIVES: The objectives of this study were to determine patterns of contraceptive utilization among sexually active HIV-1-seropositive women postpartum and to identify correlates of hormonal contraception uptake. GOAL: The goal of this study was to improve delivery of family planning services to HIV-1-infected women in resource-limited settings. STUDY DESIGN: HIV-1-infected pregnant women were followed prospectively in a perinatal HIV-1 transmission study. Participants were referred to local clinics for contraceptive counseling and management. RESULTS: Among 319 HIV-1-infected women, median time to sexual activity postpartum was 2 months and 231 (72%) women used hormonal contraception for at least 2 months during follow-up, initiating use at approximately 3 months postpartum (range, 1-11 months). Overall, 101 (44%) used DMPA, 71 (31%) oral contraception, and 59 (25%) switched methods during follow-up. Partner notification, infant mortality, and condom use were similar between those using and not using contraception. CONCLUSIONS: Using existing the healthcare infrastructure, it is possible to achieve high levels of postpartum hormonal contraceptive utilization among HIV-1-seropositive women.