Bridging Income Generation with Group Integrated Care for cardiovascular risk reduction: Rationale and design of the BIGPIC study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with >80% of CVD deaths occurring in low and middle income countries (LMICs). Diabetes mellitus and pre-diabetes are risk factors for CVD, and CVD is the major cause of morbidity and mortality among individuals with DM. There is a critical period now during which reducing CVD risk among individuals with diabetes and pre-diabetes may have a major impact. Cost-effective, culturally appropriate, and context-specific approaches are required. Two promising strategies to improve health outcomes are group medical visits and microfinance. METHODS/DESIGN: This study tests whether group medical visits integrated into microfinance groups are effective and cost-effective in reducing CVD risk among individuals with diabetes or at increased risk for diabetes in western Kenya. An initial phase of qualitative inquiry will assess contextual factors, facilitators, and barriers that may impact integration of group medical visits and microfinance for CVD risk reduction. Subsequently, we will conduct a four-arm cluster randomized trial comparing: (1) usual clinical care, (2) usual clinical care plus microfinance groups only, (3) group medical visits only, and (4) group medical visits integrated into microfinance groups. The primary outcome measure will be 1-year change in systolic blood pressure, and a key secondary outcome measure is 1-year change in overall CVD risk as measured by the QRISK2 score. We will conduct mediation analysis to evaluate the influence of changes in social network characteristics on intervention outcomes, as well as moderation analysis to evaluate the influence of baseline social network characteristics on effectiveness of the interventions. Cost-effectiveness analysis will be conducted in terms of cost per unit change in systolic blood pressure, percent change in CVD risk score, and per disability-adjusted life year saved. DISCUSSION: This study will provide evidence regarding effectiveness and cost-effectiveness of interventions to reduce CVD risk. We aim to produce generalizable methods and results that can provide a model for adoption in low-resource settings worldwide.

Antiretroviral treatment failure, drug resistance, and subtype diversity in the only pediatric HIV clinic in Rhode Island.

BACKGROUND: Drug resistance development in the human immunodeficiency virus (HIV)-infected pediatric population in the United States can impact long-term antiretroviral therapy (ART) efficacy. Limited formularies and adherence constraints in children jeopardize lifelong-needed ART. METHODS: We examined treatment failure, drug resistance, and their correlates in ART-naive and ART-experienced children attending the pediatric HIV clinic in Rhode Island between 1991 and 2012. Pol sequences were obtained for phylogenetic, subtype, and resistance analyses. Associations between selected covariates and virologic failure and resistance were evaluated using generalized additive models and Fisher exact tests. RESULTS: Data were available for all 56 clinic-attending children. At diagnosis, 33% were aged <1 year, 31% aged 1-4 years, and 37% aged ≥ 5 years; 54% were male, 73% black or Hispanic, 55% US-born, 20% refugees, and 64% perinatally infected. Of 44 ART-experienced children, 57% had virologic failure, most never virologically suppressed. Failure was associated with missed appointments (P = .05) and missed doses (P < .01). Of 40 children with available genotypes, 35% were infected with non-B subtypes; 6% of ART-naive children had resistance; and 73% of ART-experienced children had ≥ 1 major mutation: (16% conferring triple-class, 47% dual-class, and 37% single-class resistance). An epidemiologically confirmed resistance transmission from a perinatally infected teenage male to a newly infected teenage female was demonstrated. CONCLUSIONS: We report high HIV type 1 diversity, extensive drug resistance among ART-experienced children, and horizontal transmission of resistance in the Rh ode Island pediatric HIV clinic. As HIV-infected children mature into adulthood, close monitoring of ART, adherence, and diagnosis disclosure are essential to optimize patient care.

Transmitted HIV drug resistance at the Thai Red Cross anonymous clinic in Bangkok: results from three consecutive years of annual surveillance.

OBJECTIVES: The aim of this study was to prospectively survey transmitted drug resistance (TDR) among recently infected individuals (mostly MSM). METHODS: TDR was determined in prospective annual cohorts of recently HIV-1-infected individuals consecutively recruited from 2008 to 2010. Resistance interpretation was carried out using Stanford Database tools and the WHO surveillance drug resistance mutation list. Kruskal-Wallis and Fisher's exact tests were used to compare demographic and laboratory outcomes. RESULTS: A total of 299 subjects were enrolled, with 89% MSM. Median viral load was significantly higher in 2010 than in 2008 (P=0.004). Of the 284 analysable reverse transcriptase/protease sequences, TDR to any drug was found in 14/284 (4.9%); 4.0% in 2008, 5.9% in 2009 and 5.3% in 2010, with an increasing trend of TDR to NRTIs and NNRTIs from 2008 to 2010 (P=0.07). Good correlation was found between our data and the WHO threshold surveillance method. Only rilpivirine had significantly higher (P<0.05) predicted resistance in 2010 than in 2008 and 2009. CONCLUSIONS: A trend towards an increase in TDR in Thailand where the major epidemic is among MSM was observed, but did not reach the WHO-defined high-level threshold (>15%). Attention to prevent the development and spread of drug resistance is needed.

Factors Influencing Uptake of Rapid HIV and Hepatitis C Screening Among Drug Misusing Adult Emergency Department Patients: Implications for Future HIV/HCV Screening Interventions.

In this randomized, controlled trial among 957 English- or Spanish-speaking drug misusing adult emergency department (ED) patients, we determined if a tailored brief intervention (BI) increased uptake of rapid HIV/HCV screening, and identified factors associated with greater screening uptake. Rapid HIV/HCV screening uptake was greater in the control than the BI arm (45 vs. 38 %; p < 0.04). Screening uptake depended on elapsed study time and which research staff member offered testing. In the control arm, uptake was lowest for those spending <30 or ≥90 min in the study. In the BI arm, screening uptake generally increased over time. Tailored BI content specifically addressing participant HIV/HCV knowledge, HIV/HCV risk behaviors, or need for HIV/HCV screening was not associated with greater screening uptake. These study findings suggested factors that should be considered when designing future ED-based screening initiatives, such as elapsed study time, who offers testing, and the content of interventions.

Cost-effectiveness of group medical visits and microfinance interventions versus usual care to manage hypertension in Kenya: a secondary modelling analysis of data from the Bridging Income Generation with Group Integrated Care (BIGPIC) trial.

BACKGROUND: The Bridging Income Generation with Group Integrated Care (BIGPIC) trial in rural Kenya showed that integrating usual care with group medical visits or microfinance interventions reduced systolic blood pressure and cardiovascular risk in participants. We aimed to estimate the incremental cost-effectiveness of three BIGPIC interventions for a modelled cohort and by sex, as well as the cost of implementing these interventions. METHODS: For this analysis, we used data collected during the BIGPIC trial, a four-group, cluster-randomised trial conducted in the western Kenyan catchment area of the Academic Model Providing Access to Healthcare. BIGPIC enrolled participants from 24 rural health facilities in rural western Kenya aged 35 years or older with either increased blood pressure or diabetes. Participants were assigned to receive either usual care, group medical visits, microfinance, or a combination of group medical visits and microfinance (GMV-MF). Our model estimated the incremental cost-effectiveness of the three BIGPIC interventions via seven health states (ie, a hypertensive state, five chronic cardiovascular-disease states, and a death state) by simulating transitions between health states for a hypothetical cohort of individuals with hypertension on the basis of QRISK3 scores. In every cycle, participants accrued costs and disability-adjusted life-years (DALYs) associated with their health state. Incremental cost-effectiveness ratios (ICERs) were calculated for the entire modelled cohort and by sex by dividing the incremental cost by the incremental effectiveness of the next most expensive intervention. The main outcome of this analysis was ICERs for each intervention evaluated. This analysis is registered at ClinicalTrials.gov (NCT02501746). FINDINGS: Between Feb 6, 2017, and Dec 29, 2019, 2890 people were recruited to the BIGPIC trial. 2020 (69·9%) of 2890 participants were female and 870 (30·1%) were male. At baseline, mean QRISK3 score was 11·5 (95% CI 11·1-11·9) for the trial population, 11·9 (11·5-12·2) for male participants, and 11·3 (11·0-11·6) for female participants. For the population of Kenya, group medical visits were estimated to cost US$7 more per individual than usual care and result in 0·005 more DALYs averted (ICER $1455 per DALY averted). Microfinance was estimated to cost $19 more than group medical visits but was only estimated to avert 0·001 more DALYs. Relative to group medical visits, GMV-MF was estimated to cost $29 more and avert 0·009 more DALYs ($3235 per DALY averted). Relative to usual care, GMV-MF was estimated to cost $37 more and avert 0·014 more DALYs ($2601 per DALY averted). In the first year of the intervention, usual care was estimated to be the least expensive intervention to implement ($87 per participant; $10 238 per health-facility catchment area [HFCA]), then group medical visits ($99 per participant; $12 268 per HFCA), then microfinance ($120 per participant; $14 172 per HFCA), with GMV-MF estimated to be the most expensive intervention to implement ($139 per participant; $16 913 per HFCA). INTERPRETATION: Group medical visits and GMV-MF were estimated to be cost-effective strategies to improve blood-pressure control in rural Kenya. However, which intervention to pursue depends on resource availability. Policy makers should consider these factors, in addition to sex differences in programme effectiveness, when selecting optimal implementation strategies. FUNDING: US National Institutes of Health.

Added Value of Next Generation Sequencing in Characterizing the Evolution of HIV-1 Drug Resistance in Kenyan Youth.

Drug resistance remains a global challenge in children and adolescents living with HIV (CALWH). Characterizing resistance evolution, specifically using next generation sequencing (NGS) can potentially inform care, but remains understudied, particularly in antiretroviral therapy (ART)-experienced CALWH in resource-limited settings. We conducted reverse-transcriptase NGS and investigated short-and long-term resistance evolution and its predicted impact in a well-characterized cohort of Kenyan CALWH failing 1st-line ART and followed for up to ~8 years. Drug resistance mutation (DRM) evolution types were determined by NGS frequency changes over time, defined as evolving (up-trending and crossing the 20% NGS threshold), reverting (down-trending and crossing the 20% threshold) or other. Exploratory analyses assessed potential impacts of minority resistance variants on evolution. Evolution was detected in 93% of 42 participants, including 91% of 22 with short-term follow-up, 100% of 7 with long-term follow-up without regimen change, and 95% of 19 with long-term follow-up with regimen change. Evolving DRMs were identified in 60% and minority resistance variants evolved in 17%, with exploratory analysis suggesting greater rate of evolution of minority resistance variants under drug selection pressure and higher predicted drug resistance scores in the presence of minority DRMs. Despite high-level pre-existing resistance, NGS-based longitudinal follow-up of this small but unique cohort of Kenyan CALWH demonstrated continued DRM evolution, at times including low-level DRMs detected only by NGS, with predicted impact on care. NGS can inform better understanding of DRM evolution and dynamics and possibly improve care. The clinical significance of these findings should be further evaluated.

Prediction of treatment failure using 2010 World Health Organization Guidelines is associated with high misclassification rates and drug resistance among HIV-infected Cambodian children.

BACKGROUND: Antiretroviral therapy (ART) in resource-limited settings (RLSs) is monitored clinically and immunologically, according to World Health Organization (WHO) or national guidelines. Revised WHO pediatric guidelines were published in 2010, but their ability to accurately identify virological failure is unclear. METHODS: We evaluated performance of WHO 2010 guidelines and compared them with WHO 2006 and Cambodia 2011 guidelines among children on ≥6 months of first-line ART at Angkor Hospital for Children between January 2005 and September 2010. We determined sensitivity, specificity, positive and negative predictive values, and accuracy using bootstrap resampling to account for multiple tests per child. Human immunodeficiency virus (HIV) resistance was compared between those correctly and incorrectly identified by each guideline. RESULTS: Among 457 children with 1079 viral loads (VLs), 20% had >400 copies/mL. For children with WHO stage 1/2 HIV, misclassification as failure (met CD4 failure criteria, but VL undetectable) was 64% for WHO 2006 guidelines, 33% for WHO 2010 guidelines, and 81% for Cambodia 2011 guidelines; misclassification as success (did not meet CD4 failure, but VL detectable) was 11%, 12%, and 12%, respectively. For children with WHO stage 3/4 HIV, misclassification as failure was 35% for WHO 2006 guidelines, 40% for WHO 2010 guidelines, and 43% for Cambodia 2011 guidelines; misclassification as success was 13%, 24%, and 21%, respectively. Compared with WHO 2006 guidelines, WHO 2010 guidelines significantly increased the risk of misclassification as success in stage 3/4 HIV (P < .05). The WHO 2010 guidelines failed to identify 98% of children with extensive reverse-transcriptase resistance. CONCLUSIONS: In our cohort, lack of virological monitoring would result in unacceptable treatment failure misclassification, leading to premature ART switch and resistance accumulation. Affordable virological monitoring suitable for use in RLSs is desperately needed.

Real-Life Feasibility of HIV Drug Resistance Testing Using Dried Filter Analytes in Kenyan Children and Adolescents Living with HIV.

HIV-1 drug resistance remains a global challenge, yet access to testing is limited, particularly in resource-limited settings. We examined feasibility and limitations of genotyping using dried filter analytes in treatment-experienced Kenyan youth with HIV. Youth infected with HIV perinatally were enrolled in 2016-2018 at the Academic Model Providing Access to Healthcare in Eldoret, western Kenya. Samples were shipped in real-time at ambient temperature to the US, and those with viral load (VL)>1,000 copies/mL were tested based on convenience. Dried blood spots genotyping was attempted when unsuccessful from Hemaspots. Multiple logistic regression was used to examine predictors of genotyping success. Samples from 49 participants (median age 15 years, 43% female, median CD4 496 cells/µL [18%], median 8 years on therapy, median VL 11,827 copies/mL) were shipped after median 7 days from collection, arrived in 20 shipments after median 5 days, and extracted after median 2 days (1 day for samples processed on arrival; and 42 days for frozen Hemaspots). Overall, 29/49 (59%) samples with VL > 1,000 copies/mL and 25/32 (78%) with VL > 5,000 copies/mL were genotyped by either Hemaspots or DBS. Successful genotyping was associated with higher Hemaspot volume and higher VL. Real-life HIV-1 drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. Findings, particularly relevant where resistance testing is limited for clinical care, raise awareness to implementation practicability of this guidelines-recommended test in care of more individuals and populations. Further optimization of filter analytes is needed to overcome related challenges. IMPORTANCE In this manuscript we use dried filter analytes shipped from Kenya to the US in real time, to demonstrate the real-life feasibility of conducting HIV drug resistance testing in a vulnerable population of young children and adolescents with HIV in a resource limited setting. Such testing, which is recommended in resource-rich settings, is unavailable in most resource limited settings for individual clinical care. We show that real-life HIV drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. These findings raise awareness to the importance of HIV drug resistance for individual care, even in such settings, and emphasize the implementation practicability of this guidelines-recommended test.

HIV-1 Treatment Failure, Drug Resistance, and Clinical Outcomes in Perinatally Infected Children and Adolescents Failing First-Line Antiretroviral Therapy in Western Kenya.

BACKGROUND: Long-term impact of drug resistance in perinatally infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing first-line non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART). SETTING: Academic Model Providing Access to Healthcare, western Kenya. METHODS: Participants were enrolled in 2010-2013 (timepoint 1) and a subsample re-enrolled after 4-7 years (timepoint 2). Viral load (VL) was performed on timepoint 1 samples, with genotyping of those with detectable VL. Primary endpoints were treatment failure (VL >1000 copies/mL) at and death before timepoint 2. Multinomial regression analysis was used to characterize resistance effect on death, failure, and loss-to-follow-up, adjusting for key variables. RESULTS: The initial cohort (n = 480) was 52% (n = 251) female, median age 8 years, median CD4% 31%, 79% (n = 379) on zidovudine/abacavir + lamivudine + efavirenz/nevirapine for median 2 years. Of these, 31% (n = 149) failed at timepoint 1. Genotypes at timepoint 1, available on n = 128, demonstrated 93% (n = 119) extensive resistance, affecting second line. Of 128, 22 failed at timepoint 2, 17 died, and 32 were lost to follow-up before timepoint 2. Having >5 resistance mutations at timepoint 1 was associated with higher mortality [relative risk ratio (RRR) = 8.7, confidence interval (CI) 2.1 to 36.3] and loss to follow-up (RRR = 3.2, CI 1.1 to 9.2). Switching to second line was associated with lower mortality (RRR <0.05, CI <0.05 to 0.1) and loss to follow-up (RRR = 0.1, CI <0.05 to 0.3). CONCLUSION: Extensive resistance and limited switch to second line in perinatally infected Kenyan CALWH failing first-line ART were associated with long-term failure and mortality. Findings emphasize urgency for interventions to sustain effective, life-long ART in this vulnerable population.

Protozoan-Viral-Bacterial Co-Infections Alter Galectin Levels and Associated Immunity Mediators in the Female Genital Tract.

Co-infections with sexually transmittable pathogens are common and more likely in women with disturbed vaginal bacteriome. Among those pathogens, the protozoan parasite Trichomonas vaginalis (TV) is most common after accounting for the highly persistent DNA viruses human papillomavirus (HPV) and genital herpes. The parasitic infection often concurs with the dysbiotic syndrome diagnosed as bacterial vaginosis (BV) and both are associated with risks of superimposed viral infections. Yet, the mechanisms of microbial synergisms in evading host immunity remain elusive. We present clinical and experimental evidence for a new role of galectins, glycan-sensing family of proteins, in mixed infections. We assessed participants of the HIV Epidemiology Research Study (HERS) at each of their incident TV visits (223 case visits) matched to controls who remained TV-negative throughout the study. Matching criteria included age, race, BV (by Nugent score), HIV status, hysterectomy, and contraceptive use. Non-matched variables included BV status at 6 months before the matched visit, and variables examined at baseline, within 6 months of and/or at the matched visit e.g. HSV-2, HPV, and relevant laboratory and socio-demographic parameters. Conditional logistic regression models using generalized estimating equations calculated odds ratios (OR) for incident TV occurrence with each log10 unit higher cervicovaginal concentration of galectins and cytokines. Incident TV was associated with higher levels of galectin-1, galectin-9, IL-1ß and chemokines (ORs 1.53 to 2.91, p <0.001). Galectin-9, IL-1ß and chemokines were up and galectin-3 down in TV cases with BV or intermediate Nugent versus normal Nugent scores (p <0.001). Galectin-9, IL-1ß and chemokines were up in TV-HIV and down in TV-HPV co-infections. In-vitro, TV synergized with its endosymbiont Trichomonasvirus (TVV) and BV bacteria to upregulate galectin-1, galectin-9, and inflammatory cytokines. The BV-bacterium Prevotella bivia alone and together with TV downregulated galectin-3 and synergistically upregulated galectin-1, galectin-9 and IL-1ß, mirroring the clinical findings of mixed TV-BV infections. P. bivia also downregulated TVV+TV-induced anti-viral response e.g. IP-10 and RANTES, providing a mechanism for conducing viral persistence in TV-BV co-infections. Collectively, the experimental and clinical data suggest that galectin-mediated immunity may be dysregulated and exploited by viral-protozoan-bacterial synergisms exacerbating inflammatory complications from dysbiosis and sexually transmitted infections.

Egocentric social network characteristics and cardiovascular risk among patients with hypertension or diabetes in western Kenya: a cross-sectional analysis from the BIGPIC trial.

OBJECTIVES: Management of cardiovascular disease (CVD) is an urgent challenge in low-income and middle-income countries, and interventions may require appraisal of patients' social networks to guide implementation. The purpose of this study is to determine whether egocentric social network characteristics (SNCs) of patients with chronic disease in western Kenya are associated with overall CVD risk and individual CVD risk factors. DESIGN: Cross-sectional analysis of enrollment data (2017-2018) from the Bridging Income Generation with GrouP Integrated Care trial. Non-overlapping trust-only, health advice-only and multiplex (trust and health advice) egocentric social networks were elicited for each participant, and SNCs representing social cohesion were calculated. SETTING: 24 communities across four counties in western Kenya. PARTICIPANTS: Participants (n=2890) were ≥35 years old with diabetes (fasting glucose ≥7 mmol/L) or hypertension. PRIMARY AND SECONDARY OUTCOMES: We hypothesised that SNCs would be associated with CVD risk status (QRISK3 score). Secondary outcomes were individual CVD risk factors. RESULTS: Among the 2890 participants, 2020 (70%) were women, and mean (SD) age was 60.7 (12.1) years. Forty-four per cent of participants had elevated QRISK3 score (≥10%). No relationship was observed between QRISK3 level and SNCs. In unadjusted comparisons, participants with any individuals in their trust network were more likely to report a good than a poor diet (41% vs 21%). SNCs for the trust and multiplex networks accounted for a substantial fraction of variation in measures of dietary quality and physical activity (statistically significant via likelihood ratio test, adjusted for false discovery rate). CONCLUSION: SNCs indicative of social cohesion appear to be associated with individual behavioural CVD risk factors, although not with overall CVD risk score. Understanding how SNCs of patients with chronic diseases relate to modifiable CVD risk factors could help inform network-based interventions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02501746; https://clinicaltrials.gov/ct2/show/NCT02501746.

Group Medical Visit and Microfinance Intervention for Patients With Diabetes or Hypertension in Kenya.

BACKGROUND: Incorporating social determinants of health into care delivery for chronic diseases is a priority. OBJECTIVES: The goal of this study was to evaluate the impact of group medical visits and/or microfinance on blood pressure reduction. METHODS: The authors conducted a cluster randomized trial with 4 arms and 24 clusters: 1) usual care (UC); 2) usual care plus microfinance (MF); 3) group medical visits (GMVs); and 4) GMV integrated into MF (GMV-MF). The primary outcome was 1-year change in systolic blood pressure (SBP). Mixed-effects intention-to-treat models were used to evaluate the outcomes. RESULTS: A total of 2,890 individuals (69.9% women) were enrolled (708 UC, 709 MF, 740 GMV, and 733 GMV-MF). Average baseline SBP was 157.5 mm Hg. Mean SBP declined -11.4, -14.8, -14.7, and -16.4 mm Hg in UC, MF, GMV, and GMV-MF, respectively. Adjusted estimates and multiplicity-adjusted 98.3% confidence intervals showed that, relative to UC, SBP reduction was 3.9 mm Hg (-8.5 to 0.7), 3.3 mm Hg (-7.8 to 1.2), and 2.3 mm Hg (-7.0 to 2.4) greater in GMV-MF, GMV, and MF, respectively. GMV and GMV-MF tended to benefit women, and MF and GMV-MF tended to benefit poorer individuals. Active participation in GMV-MF was associated with greater benefit. CONCLUSIONS: A strategy combining GMV and MF for individuals with diabetes or hypertension in Kenya led to clinically meaningful SBP reductions associated with cardiovascular benefit. Although the significance threshold was not met in pairwise comparison hypothesis testing, confidence intervals for GMV-MF were consistent with impacts ranging from substantive benefit to neutral effect relative to UC. Incorporating social determinants of health into care delivery for chronic diseases has potential to improve outcomes. (Bridging Income Generation With Group Integrated Care [BIGPIC]; NCT02501746).

Community Health Workers Improve Linkage to Hypertension Care in Western Kenya.

BACKGROUND: Elevated blood pressure (BP) is the leading global risk factor for mortality. Delay in seeking hypertension care is associated with increased mortality. OBJECTIVES: This study investigated whether community health workers, equipped with behavioral communication strategies and smartphone technology, can increase linkage of individuals with elevated BP to a hypertension care program in western Kenya and significantly reduce BP. METHODS: The study was a cluster randomized trial with 3 arms: 1) usual care (standard training); 2) "paper-based" (tailored behavioral communication, using paper-based tools); and 3) "smartphone" (tailored behavioral communication, using smartphone technology). The co-primary outcomes were: 1) linkage to care; and 2) change in systolic BP (SBP). A covariate-adjusted mixed-effects model was used, adjusting for differential time to follow-up. Bootstrap and multiple imputation were used to handle missing data. RESULTS: A total of 1,460 individuals (58% women) were enrolled (491 usual care, 500 paper-based, 469 smartphone). Average baseline SBP was 159.4 mm Hg. Follow-up measures of linkage were available for 1,128 (77%) and BP for 1,106 (76%). Linkage to care was 49% overall, with significantly greater linkage in the usual care and smartphone arms of the trial. Average overall follow-up SBP was 149.9 mm Hg. Participants in the smartphone arm experienced a modestly greater reduction in SBP versus usual care (-13.1 mm Hg vs. -9.7 mm Hg), but this difference was not statistically significant. Mediation analysis revealed that linkage to care contributed to SBP change. CONCLUSIONS: A strategy combining tailored behavioral communication and mobile health (mHealth) for community health workers led to improved linkage to care, but not statistically significant improvement in SBP reduction. Further innovations to improve hypertension control are needed. (Optimizing Linkage and Retention to Hypertension Care in Rural Kenya [LARK]; NCT01844596).

Genital tract leukocytes and shedding of genital HIV type 1 RNA.

BACKGROUND: The mechanism of human immunodeficiency virus (HIV) transmission via heterosexual intercourse is unknown. We sought to determine whether the presence of inflammatory cells in the vagina is associated with the presence of genital tract HIV type 1 (HIV-1) RNA. METHODS: Analysis of a longitudinal prospective cohort was performed. Women with HIV-1 infection were assessed with use of paired plasma and cervicovaginal lavage specimens. Viral load measurements were performed using nucleic acid sequence-based amplification. White blood cells found in the genital tract (GT WBCs) were quantified using a hemacytometer. Common lower genital tract infections assessed for association with viral shedding (i.e., genital tract viral load [GTVL]) included bacterial vaginosis, candidiasis, and trichomoniasis. Generalized estimating equations were used to estimate the prevalence and odds of detectable GTVL by GT WBC. The association was examined both in the presence and in the absence of lower genital tract infections. RESULTS: A total of 97 women and 642 visits were included in the analysis. Median duration of follow-up was 30.4 months. Thirty women (31%) had detectable GTVL at any visit. The median CD4 cell count at baseline was 525 cells/muL. Most women were antiretroviral therapy naive at baseline. After adjustment for plasma viral load, the odds of detectable GTVL increased as GT WBC increased, with an odds ratio of 1.36 (95% confidence interval, 1.1-1.7) per 1000-cell increase in GT WBC among women without lower genital tract infections. After adjustment for plasma viral load and lower genital tract infections by incorporating them in a regression model, GT WBC remained significantly associated with GTVL, with an adjusted odds ratio of 1.22 (95% confidence interval, 1.08-1.37). CONCLUSIONS: The presence of GT WBC is associated with an increased risk of detectable GTVL.

Disparities in the provision of sexually transmitted disease and pregnancy testing and prophylaxis for sexually assaulted women in Rhode Island emergency departments.

OBJECTIVES: To determine how often sexually assaulted adult female emergency department (ED) patients are being offered testing and prophylaxis for sexually transmitted diseases (STDs) and pregnancy and identify factors associated with the offering of tests and prophylaxis. METHODS: This is a retrospective study of ED visits for adult female sexual assault in all Rhode Island EDs from January 1995 through June 2001. The percentage of patients offered testing and prophylaxis was calculated. Multivariable logistic regression was used to identify factors related to testing and prophylaxis use for women sustaining an anal/vaginal assault. RESULTS: Of the 780 patients, 78.2% sustained anal/vaginal penetration, 5.0% genital touching only, and 3.7% oral sex only, and 13.1% did not know what happened to them. Of those women anal/vaginally assaulted, 83.8% were offered chlamydia/gonorrhea testing, 69.4% syphilis testing, 82.9% pregnancy testing, 77.0% chlamydia/gonorrhea prophylaxis, 47.6% emergency contraception, and 19.2% HIV prophylaxis. In multivariable logistic regression models, patients evaluated at the state's women's hospital instead of academic or community hospitals and those who sustained anal/vaginal assault instead of other assaults had a greater odds of being offered testing and prophylaxis. In some cases, older women were offered testing and prophylaxis less often than younger women. CONCLUSIONS: Testing and prophylaxis for chlamydia/gonorrhea were used much more often than prophylaxis for emergency contraception and HIV, even for patients who were anal/vaginally assaulted. Disparities in testing and prophylaxis exist by type of hospital and, in some cases, by age. Educational campaigns should be instituted to ensure that all women receive adequate testing and prophylaxis commensurate with the exposure they sustained from a sexual assault.

Improved HIV-1 Viral Load Monitoring Capacity Using Pooled Testing With Marker-Assisted Deconvolution.

OBJECTIVE: Improve pooled viral load (VL) testing to increase HIV treatment monitoring capacity, particularly relevant for resource-limited settings. DESIGN: We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling deconvolution strategy that uses information from low-cost, routinely collected clinical markers to determine an efficient order of sequential individual VL testing and dictates when the sequential testing can be stopped. METHODS: We simulated the use of pooled testing to ascertain virological failure status on 918 participants from 3 studies conducted at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when using mMPA and other pooling methods. We also evaluated the impact of practical factors, such as specific markers used, prevalence of virological failure, pool size, VL measurement error, and assay detection cutoffs on mMPA, other pooling methods, and single testing. RESULTS: Using CD4 count as a marker to assist deconvolution, mMPA significantly reduces the number of VL assays by 52% [confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to 22%) compared with individual testing, simple mini-pooling, and mini-pooling with algorithm, respectively. mMPA has higher sensitivity and negative/positive predictive values than mini-pooling with algorithm, and comparable high specificity. Further improvement is achieved with additional clinical markers, such as age and time on therapy, with or without CD4 values. mMPA performance depends on prevalence of virological failure and pool size but is insensitive to VL measurement error and VL assay detection cutoffs. CONCLUSIONS: mMPA can substantially increase the capacity of VL monitoring.

Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya.

We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds.

Markers of Atherosclerosis, Clinical Characteristics, and Treatment Patterns in Heart Failure: A Case-Control Study of Middle-Aged Adult Heart Failure Patients in Rural Kenya.

BACKGROUND: Although risk factors for heart failure are increasingly common worldwide, the contribution of atherosclerosis to heart failure in sub-Saharan Africa is largely unknown. OBJECTIVE: This study assessed the association between atherosclerotic risk factors and heart failure in a developing country. METHODS: We performed a case-control study of heart failure in rural Kenya. We assessed the risk factors for heart failure by using international criteria based on electrocardiogram (ECG), echocardiogram, physical examination findings, and laboratory testing. Atherosclerotic risk factors were determined by ECG, echocardiogram, ankle-brachial index (ABI), and lipid testing. We described the relationship of wall motion abnormalities on echocardiogram, ABI <0.9, and ischemic pattern on ECG with the presence of heart failure with multivariable logistic regression adjusting for age and sex and using adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: There were 125 cases and 191 controls (n = 316); 49% were male. The mean age was 60 (SD = 13) years. Most patients had hypertension (53%), and 16% had human immunodeficiency virus infection. Lipids were in the normal range for all. Cases were older than controls (62 years vs. 58 years, respectively). The most common abnormality associated with heart failure was dilated cardiomyopathy. Ischemic heart failure was the second most common cause in men. Cases were more likely to have an ABI <0.9 (46% vs. 31%; AOR: 1.99; 95% CI: 1.19 to 3.32), ischemia or infarct on ECG (68% vs. 43%; AOR: 3.01; 95% CI: 1.43 to 6.34), and wall motion abnormalities on echocardiogram (54% vs. 15%; AOR: 7.00; 95% CI: 3.95 to 12.39). CONCLUSIONS: Ischemic heart failure is more common in Kenya than previously recognized. Noninvasive markers of atherosclerosis are routinely found among patients with heart failure. Treatment and prevention of heart failure in sub-Saharan Africa must consider many causes including those related to atherosclerosis.

Factors associated with isolated right heart failure in women: a pilot study from western Kenya.

BACKGROUND: Small observational studies have found that isolated right heart failure (IRHF) is prevalent among women of sub-Saharan Africa. Further, several risk factors for the development of IRHF have been identified. However, no similar studies have been conducted in Kenya. OBJECTIVE: We hypothesized that specific environmental exposures and comorbidities were associated with IRHF in women of western Kenya. METHODS: We conducted a case-control study at a referral hospital in western Kenya. Cases were defined as women at least 35 years old with IRHF. Control subjects were similarly aged volunteers without IRHF. Exclusion criteria in both groups included history of tobacco use, tuberculosis, or thromboembolic disease. Participants underwent echocardiography, spirometry, 6-min walk test, rest/exercise oximetry, respiratory health interviews, and human immunodeficiency virus (HIV) testing. Home visits were performed to evaluate kitchen ventilation, fuel use, and cook smoke exposure time, all surrogate measures of indoor air pollution (IAP). A total of 31 cases and 65 control subjects were enrolled. Surrogate measures of indoor air pollution were not associated with IRHF. However, lower forced expiratory volume at 1 s percent predicted (adjusted odds ratio [AOR]: 2.02, 95% confidence interval [CI]: 1.27 to 3.20; p = 0.004), HIV positivity (AOR: 40.4, 95% CI: 3.7 to 441; p < 0.01), and self-report of exposure to occupational dust (AOR: 3.9, 95% CI: 1.14 to 14.2; p = 0.04) were associated with IRHF. In an analysis of subgroups of participants with and without these factors, lower kitchen ventilation was significantly associated with IRHF among participants without airflow limitation (AOR: 2.63 per 0.10 unit lower ventilation, 95% CI: 1.06 to 6.49; p = 0.04), without HIV (AOR: 2.55, 95% CI: 1.21 to 5.37; p = 0.02), and without occupational dust exposure (AOR: 2.37, 95% CI: 1.01 to 5.56; p = 0.05). CONCLUSIONS: In this pilot study among women of western Kenya, lower kitchen ventilation, airflow limitation, HIV, and occupational dust exposure were associated with IRHF, overall or in participant subgroups. Direct or indirect causality requires further study.

The spectrum of undiagnosed hepatitis C virus infection in a US HIV clinic.

United States guidelines endorse one-time HCV antibody screening at HIV diagnosis. Rescreening HCV-seronegative patients on a regular basis is still not policy, although HIV-infected persons have reasonably substantial HCV incidence. We evaluated routine risk factor-independent HCV antibody re-testing in a Rhode Island HIV clinic. We instituted annual HCV antibody testing for HCV-seronegative patients who had not been rescreened in a year or more. Testing based on clinical suspicion continued. We conducted a chart review of new antibody-positive cases in the first year of rescreening, July 2006 to June 2007. Of 245 rescreened patients, 11 (4.5%) seroconverted. Five (45%) were female. Median time between last negative and first positive result was 32 months (range 8-98 months). Six (55%) had documented risk factors and 6 (55%) elevated ALT (> 45 IU/L) between antibody tests; none prompted re-testing. One seroconverter died of hepatocellular carcinoma 3.7 years after HCV diagnosis. A twelfth was rescreened for suspected acute HCV based on ALT of 515 IU/L. He had newly detectable HCV RNA then seroconversion, and achieved SVR following 6 months of treatment in the acute phase for genotype 1 infection. Incident HCV is not uncommon among HIV-infected patients in care. Rescreening identified undiagnosed HCV in this population. HCV RNA should be checked promptly in HCV-seronegative persons with ALT elevation. We observed consequences of late diagnosis (hepatocellular carcinoma) and benefits of early diagnosis (cure with treatment of acute HCV). Adding annual rescreening to the Ryan White Program would facilitate earlier identification of undiagnosed HCV and create an instant widespread surveillance system, providing HCV incidence data.