Trends in clinical characteristics and outcomes of Pre-ART care at a large HIV clinic in Nairobi, Kenya: a retrospective cohort study.

BACKGROUND: The success of antiretroviral therapy in resource-scarce settings is an illustration that complex healthcare interventions can be successfully delivered even in fragile health systems. Documenting the success factors in the scale-up of HIV care and treatment in resource constrained settings will enable health systems to prepare for changing population health needs. This study describes changing demographic and clinical characteristics of adult pre-ART cohorts, and identifies predictors of pre-ART attrition at a large urban HIV clinic in Nairobi, Kenya. METHODS: We conducted a retrospective cohort analysis of data on HIV infected adults (≥15 years) enrolling in pre-ART care between January 2004 and September 2015. Attrition (loss to program) was defined as those who died or were lost to follow-up (having no contact with the facility for at least 6 months). We used Kaplan-Meier survival analysis to determine time to event for the different modes of transition, and Cox proportional hazards models to determine predictors of pre-ART attrition. RESULTS: Over the 12 years of observation, there were increases in the proportions of young people (age 15 to 24 years); and patients presenting with early disease (by WHO clinical stage and higher median CD4 cell counts), p = 0.0001 for trend. Independent predictors of attrition included: aHR (95% CI): male gender 1.98 (1.69-2.33), p = 0.0001; age 20-24 years 1.80 (1.37-2.37), p = 0.0001), or 25-34 years 1.22 (1.01-1.47), p = 0.0364; marital status single 1.55 (1.29-1.86), p = 0.0001) or divorced 1.41(1.02-1.95), p = 0.0370; urban residency 1.83 (1.40-2.38), p = 0.0001; CD4 count of 0-100 cells/µl 1.63 (1.003-2.658), p = 0.0486 or CD4 count >500 cells/µl 2.14(1.46-3.14), p = 0.0001. CONCLUSIONS: In order to optimize the impact of HIV prevention, care and treatment in resource scarce settings, there is an urgent need to implement prevention and treatment interventions targeting young people and patients entering care with severe immunosuppression (CD4 cell counts <100 cells/µl). Additionally, care and treatment programmes should strengthen inter-facility referrals and linkages to improve care coordination and prevent leakages in the HIV care continuum.

Enhancing Maternal and Child Health using a Combined Mother & Child Health Booklet in Kenya.

Under Kenyan guidelines, HIV-exposed infants should be tested for HIV DNA at 6 weeks or at first clinical contact thereafter, as infants come for immunization. Following the introduction of early infant diagnoses programmes, however, many infants were not being tested and linked to care and treatment. We developed the Mother & Child Health Booklet to help relate mothers' obstetrical history to infants' healthcare providers to facilitate follow-up and timely management. The booklet contains information on the mother's pregnancy, delivery and postpartum course and her child's growth and development, immunization, nutrition and other data need to monitor the child to 5 years of age. It replaced three separate record clinical cards. In a 1 year pilot evaluation of the booklet in Nyanza province in 2007-08, the number of HIV DNA tests on infants increased by 34% from 9966 to 13 379. The booklet was subsequently distributed nationwide in 2009. Overall, the numbers of infants tested for HIV DNA rose from 27 000 in 2007 to 60 000 in 2012, which represents approximately 60% of the estimated HIV-exposed infants in Kenya. We believe that the booklet is an important strategy for identifying and treating infected infants and, thus, in progress toward Millennium Development Goal 4.

Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma.

RATIONALE: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract. OBJECTIVES: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens. METHODS: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131). MEASUREMENTS AND MAIN RESULTS: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001). CONCLUSIONS: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.

The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose.

BACKGROUND: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. OBJECTIVES: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. METHODS: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. RESULTS: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20-fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (χ(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001). CONCLUSION: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.

Factors Associated with Outcomes of Pre-ART HIV Care.

The World Health Organization recommended removing all CD4 requirements for initiation of antiretroviral therapy (ART) in resource-limited settings. We examined the pre-ART period to identify and assess factors associated with outcomes of pre-ART care. Four modes of transition out of pre-ART care were considered. Beta estimates from the competing risks Cox models were used to investigate whether the effects of covariates differed by mode of transition. Median CD4 counts at entry showed no meaningful change over time. Advanced disease progression and presence of opportunistic infections were significant predictors of pre-ART mortality. Men were more likely to die before initiating ART, transfer to another facility, or be lost to follow-up than were women. Removing CD4 thresholds is not likely to substantially reduce program mortality prior to ART initiation unless and until patients enroll earlier in disease progression. Care programs should focus on diagnosis and treatment of opportunistic infections to reduce pre-ART mortality.

Trends, treatment outcomes, and determinants for attrition among adult patients in care at a large tertiary HIV clinic in Nairobi, Kenya: a 2004-2015 retrospective cohort study.

BACKGROUND: Understanding trends in patient profiles and identifying predictors for adverse outcomes are key to improving the effectiveness of HIV care and treatment programs. Previous work in Kenya has documented findings from a rural setting. This paper describes trends in demographic and clinical characteristics of antiretroviral therapy (ART) treatment cohorts at a large urban, referral HIV clinic and explores treatment outcomes and factors associated with attrition during 12 years of follow-up. METHODS: This was a retrospective cohort analysis of HIV-infected adults who started ART between January 1, 2004, and September 30, 2015. ART-experienced patients and those with missing data were excluded. The Cochran-Armitage test was used to determine trends in baseline characteristics over time. Cox proportional hazards models were used to determine the effect of baseline characteristics on attrition. RESULTS: ART uptake among older adolescents (15-19 years), youth, and young adults increased over time (p=0.0001). Independent predictors for attrition included (adjusted hazard ratio [95% CI]) male sex: 1.30 (1.16-1.45), p=0.0001; age: 15-19 years: 1.83 (1.26-2.66), p=0.0014; 20-24 years: 1.93 (1.52-2.44), p=0.0001; and 25-29 years: 1.31 (1.11-1.54), p=0.0012; marital status - single: 1.27 (1.11-1.44), p=0.0005; and divorced/separated: 1.56 (1.30-1.87), p=0.0001; urban residence: 1.40 (1.20-1.64), p=0.0001; entry into HIV care following hospitalization: 1.31 (1.10-1.57), p=0.0026, or transfer from another facility: 1.60 (1.26-2.04), p=0.0001; initiation of ART more than 12 months after the date of HIV diagnosis: 1.36 (1.19-1.55), p=0.0001, and history of a current or past opportunistic infection (OI): 1.15 (1.02-1.30), p=0.0284. CONCLUSION: Although ART uptake among adolescents and young people increased over time, this group was at increased risk for attrition. Single marital status, urban residence, history of hospitalization or OI, and delayed initiation of ART also predicted attrition. This calls for focused evidence-informed strategies to address attrition and improve outcomes.

Preventing mother-to-child transmission of HIV in Western Kenya: operational issues.

OBJECTIVES: To improve uptake in a program to prevent mother-to-child HIV transmission and describe lessons relevant for prevention of mother-to-child transmission programs in resource-poor settings. METHODS: Implementation of a pilot project that evaluates approaches to increase program uptake at health facility level at New Nyanza Provincial General Hospital, a public hospital in western Kenya, an area with high HIV prevalence. Client flow was revised to integrate counseling, HIV testing, and dispensing of single-dose nevirapine into routine antenatal services. The number of facilities providing PMCT services was expanded to increase district-wide coverage. Main outcome measures were uptake of counseling, HIV testing, nevirapine, and estimated program impact. RESULTS: Uptake of counseling and testing improved from 55 to 68% (P < 0.001), nevirapine uptake from 57% to 70% (P < 0.001), and estimated program impact from 15% to 23% (P = 0.03). Aggregate reports compare well with computer-entered data. CONCLUSION: Addressing institutional factors can improve uptake, but expected program impact remains low for several reasons, including relatively low efficacy of the intervention and missed opportunities in the labor room.