Dr
Tecla Temu
Current Organisation
University of Nairobi/University of Washington
Current Job Title
Clinical Assistant Professor
Biography
Publications
OBJECTIVE:Hypertension affects 23% of Kenyans and is the most prevalent modifiable risk factor for cardiovascular disease. Despite this, hypertension awareness and treatment adherence is very low. We conducted a qualitative study to explore lay beliefs about hypertension among HIV-infected adults to inform the development of culture sensitive hypertension prevention and control program. METHODS:Eight focus group discussions were held for 53 HIV-infected adults at the HIV clinic in Kenya. RESULTS:Respondents had difficulties in describing hypertension. Hypertension was considered a temporary illness that is fatal and more serious than HIV. Stress was perceived as a main cause for hypertension with a large majority claiming stress reduction as the best treatment modality. Alcohol and tobacco use were not linked to hypertension. Obesity was cited as a cause of hypertension but weight control was not considered as a treatment modality even though the majority of our participants were overweight. Most participants did not believe hypertension could be prevented. CONCLUSION:Our findings suggest a limited understanding of hypertension among people living with HIV and points to an urgent need to integrate hypertension education programmes in HIV care facilities in Kenya. To effect change, these programmes will need to tie in the culture meaning of hypertension.
BACKGROUND:There is an urgent need to understand genetic associations with atrial fibrillation in ethnically diverse populations. There are no such data from sub-Saharan Africa, despite the fact that atrial fibrillation is one of the fastest growing diseases. Moreover, patients with valvular heart disease are underrepresented in studies of the genetics of atrial fibrillation. METHODS:We designed a case-control study of patients with and without a history of atrial fibrillation in Kenya. Cases with atrial fibrillation included those with and without valvular heart disease. Patients underwent clinical phenotyping and will have laboratory analysis and genetic testing of >240 candidate genes associated with cardiovascular diseases. A 12-month follow-up assessment will determine the groups' morbidity and mortality. The primary analyses will describe genetic and phenotypic associations with atrial fibrillation. RESULTS:We recruited 298 participants: 72 (24%) with nonvalvular atrial fibrillation, 78 (26%) with valvular atrial fibrillation, and 148 (50%) controls without atrial fibrillation. The mean age of cases and controls were 53 and 48 years, respectively. Most (69%) participants were female. Controls more often had hypertension (45%) than did those with valvular atrial fibrillation (27%). Diabetes and current tobacco smoking were uncommon. A history of stroke was present in 25% of cases and in 5% of controls. CONCLUSION:This is the first study determining genetic associations in valvular and nonvalvular atrial fibrillation in sub-Saharan Africa with a control population. The results advance knowledge about atrial fibrillation and will enhance international efforts to decrease atrial fibrillation-related morbidity.
BACKGROUND:Quality improvement initiatives have been developed to improve acute coronary syndrome care largely in high-income country settings. We sought to synthesize the effect size and quality of evidence from randomized controlled trials (RCTs) and nonrandomized studies for hospital-based acute coronary syndrome quality improvement interventions on clinical outcomes and process of care measures for their potential implementation in low- and middle-income country settings. METHODS AND RESULTS:We conducted a bibliometric search of databases and trial registers and a hand search in 2016 and performed an updated search in May 2018 and May 2019. We performed data extraction, risk of bias assessment, and quality of evidence assessments in duplicate. We assessed differences in outcomes by study design comparing RCTs to nonrandomized quasi-experimental studies and by country income status. A meta-analysis was not feasible due to substantial, unexplained heterogeneity among the included studies, and thus, we present a qualitative synthesis. We screened 5858 records and included 32 studies (14 RCTs [n=109 763] and 18 nonrandomized quasi-experimental studies [n=54-423]). In-hospital mortality ranged from 2.1% to 4.8% in the intervention groups versus 3.3% to 5.1% in the control groups in 5 RCTs (n=55 942). Five RCTs (n=64 313) reported 3.0% to 31.0% higher rates of reperfusion for patients with ST-segment-elevation myocardial infarction in the intervention groups. The effect sizes for in-hospital and discharge medical therapies in a majority of RCTs were 3.0% to 10.0% higher in the intervention groups. There was no significant difference in 30-day mortality evaluated by 4 RCTs (n=42 384), which reported 2.5% to 15.0% versus 5.9% to 22% 30-day mortality rates in the intervention versus control groups. In contrast, nonrandomized quasi-experimental studies reported larger effect sizes compared to RCTs. There were no significant consistent differences in outcomes between high-income and middle-income countries. Low-income countries were not represented in any of the included studies. CONCLUSIONS:Hospital-based acute coronary syndrome quality improvement interventions have a modest effect on process of care measures but not on clinical outcomes with expected differences by study design. Although quality improvement programs have an ongoing and important role for acute coronary syndrome quality of care in high-income country settings, further research will help to identify key components for contextualizing and implementing such interventions to new settings to achieve their desired effects. Systematic Review Registration: URL: https://www.crd.york.ac.uk/PROSPERO/. Unique identifier: CRD42016047604.
Insulin-like growth factor 1 (IGF-1) is a potent mitogen and differentiation factor with particular relevance to orthopedic tissue engineering. A biologically based Ca2+-alginate microcapsule vehicle, utilizing genetically modified primary normal human fibroblasts (NHFs), was developed and characterized for localized synthesis and delivery of human IGF-1 (hIGF-1). Normal human fibroblasts were transfected to overexpress the hIGF-1 gene, leading to cells that expressed 4 ng of hIGF-1 per 10(6) cells per 24 hours. Encapsulation within alginate led to a six-fold enhancement in the generation and release of hIGF-1 to 22 ng of hIGF-1 per 10(6) cells per 24 hours. Release was constitutive, predictable, and exhibited highly repeatable first-order kinetics with no initial burst. Released growth factor was biologically active and exhibited a proliferative effect comparable to commercially available recombinant hIGF-1. The magnitude of hIGF-1 release met the requirements of orthopedic tissue generation, and this approach is considered an attractive alternative to other proposed methods of growth factor delivery.
Metabolic syndrome (MetS), a cluster of cardiovascular disease risk factors, is increasingly common in people living with HIV; however, data on prevalence and the role of antiretroviral therapy (ART) as a risk factor for MetS in sub-Saharan Africa are lacking. We conducted a cross-sectional study to assess the prevalence and risk factors for MetS among ART-naive and ART-experienced HIV-infected adults without preexisting cardiometabolic disorders in Western Kenya using validated questionnaires and laboratory tests after overnight fasting. We used logistic regression to identify associations between traditional risk factors, HIV disease characteristics, ART, and MetS. Study participants included 164 ART-experienced patients, majority (56%) on tenofovir/lamivudine/nevirapine regimen, and 136 ART-naive patients. The median age was 40 (interquartile range, 33-46) years and 64% were women. Median HIV infection and ART use were 4.6 (1.7-7.9) and 4.8 (2.7-7.8) years, respectively. Prevalence of MetS did not differ between ART-experienced (16.9%) and -naive (15.2%) groups. ART-experienced patients had higher rates of elevated fasting blood sugars and lower rates of low high-density lipoprotein-cholesterol. The prevalence of abnormal waist circumference, elevated blood pressure, and hypertriglyceridemia were comparable between the two groups. Older age, female sex, and high body mass index were independently associated with diagnosis of MetS. Traditional risk factors rather than ART-related effects were more important predictors of MetS in this cohort and may have been influenced by ART type and exclusion of preexisting hypertension and diabetes. HIV-infected patients without preexisting cardiometabolic disorders should be monitored for metabolic abnormalities regardless of ART.
BACKGROUND:The prevalence of ischaemic heart disease and its acute manifestation, acute coronary syndrome (ACS), is growing throughout sub-Saharan Africa, including Kenya. To address this increasing problem, we sought to understand the facilitators, context of and barriers to ACS care at Kenyatta National Hospital, with the aim of improving the quality of care of ACS. METHODS:We conducted in-depth interviews with healthcare providers involved in the management of ACS patients from January to February 2017 at Kenyatta National Hospital in Nairobi, Kenya. We selected an initial sample of key participants for interviewing and used a snowballing technique to identify additional participants until we achieved saturation. After transcription of audio recordings of the interviews, two authors conducted data coding and analysis using a framework approach. RESULTS:We conducted 16 interviews with healthcare providers. Major themes included the need to improve the diagnostic and therapeutic capabilities of the hospital, including increasing the number of ECG machines and access to thrombolytics. Participants highlighted an overall wide availability of other guideline-directed medical therapies, including antiplatelets, beta-blockers, statins, anticoagulants and ACE inhibitors. All participants also stated the need for and openness to accepting future interventions for improvement of quality of care, including checklists and audits to improve ACS care at Kenyatta National Hospital. CONCLUSION:Major barriers to ACS care at Kenyatta National Hospital include inadequate diagnostic and therapeutic capabilities, lack of hospital-wide ACS guidelines, undertraining of healthcare providers and delayed presentation of patients seeking care. We also identified potential targets, including checklists and audits for future improvements in quality of care from the perspective of healthcare providers.
OBJECTIVE:To synthesize published literature on noncommunicable disease (NCD) behavior change communication (BCC) interventions in sub-Saharan Africa (SSA) among persons living with HIV (PLHIV) and in the general population to inform efforts to adopt similar HIV and NCD BCC intervention activities. METHODS:We conducted a literature review of NCD BCC interventions and included 20 SSA-based studies. Inclusion criteria entailed describing a BCC intervention targeting any four priority NCDs (cardiovascular disease, type 2 diabetes, cervical cancer, and depression) or both HIV and any of the NCDs. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was used to assess potential public health impact of these studies. We also solicited expert opinions from 10 key informants on the topic of HIV/NCD health promotion in five SSA countries. RESULTS:The BCC interventions reviewed targeted multiple parts of the HIV and NCD continuum at both individual and community levels. Various strategies (i.e. health education, social marketing, motivational interviewing, mobile health, and peer support) were employed. However, few studies addressed more than one dimension of the RE-AIM framework. Opinions solicited from the key informants supported the feasibility of integrating HIV and NCD BCC interventions in SSA potentially improving access, service provision and service demand, especially for marginalized and vulnerable populations. CONCLUSION:Although HIV/NCD integration can improve effectiveness of preventive services at individual and community levels, potential public health impact of such approaches remain unknown as reach, adoptability, and sustainability of both integrated and nonintegrated NCD BCC approaches published to date have not been well characterized.
Objectives: Heightened systemic inflammation is common in obese individuals and persons with HIV (PWH) and is independently associated with an increased risk of cardiovascular diseases (CVD). We investigated the combined effect of central obesity, a surrogate measure of visceral fat, and HIV on circulating levels of inflammatory cytokines among Kenyan adults.
Design: Cross-sectional study.
Methods: We analyzed and compared data from 287 virally suppressed PWH and 277 non-infected Kenyan adults including biomarkers of gut epithelial dysfunction (intestinal fatty acid binding protein), monocyte activation (soluble CD163 and CD14), and inflammation (interleukin [IL]-1β, IL-6, TNF-α, and hsCRP) by HIV/central obesity status (HIV+/obese, HIV-/obese, HIV+/non-obese, and HIV-/non-obese). Central obesity was defined as waist circumference >80 cm for women and >94 cm for men. We assessed the association of HIV/obesity status with elevated biomarkers (>75th percentile) using logistic regression.
Results: Median age for participants was 44 years and 37% were centrally obese. Levels of all biomarkers were higher among the HIV+/obese compared to the HIV-/non-obese (p < 0.05 for all comparisons). The HIV+/obese group had the greatest odds of having elevated inflammatory biomarkers compared to other groups even after adjustment of age, BMI, and other conventional CVD risk factors (p < 0.05 for all). Additional adjustment for sCD163 in the multivariate model substantially attenuated the association for HIV+/obesity with IL-1β, IL-6, and TNF-α but not hsCRP. The contribution of HIV+/obesity to inflammation was independent of the degree of immunosuppression.
Conclusions: Central obesity is prevalent among virally suppressed African PWH and is associated with greater inflammation and monocyte activation independent of other comorbidities and HIV-specific factors.
Introduction: Markers of monocyte/macrophage activation and vascular inflammation are associated with HIV-related cardiovascular diseases (CVD) and mortality. We compared these markers among African people living with HIV (PLWH) and HIV-negative adults, and examined risk factors associated with elevated biomarkers (>75th percentile) in PLWH on antiretroviral therapy (ART).
Design: Cross-sectional study.
Methods: We measured serum concentrations of a gut integrity biomarker (intestinal-fatty acid binding protein), monocyte/macrophage activation biomarkers (soluble CD14 and CD163), and vascular inflammation biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1)]. We assessed the relationship of these inflammatory parameters with HIV, using logistic regression adjusting for traditional CVD risk factors.
Results: Among the 541 participants, median age was 43 years and half were female. Among 275 PLWH, median CD4 T-cell count and duration of ART use was 509 cells/μl and 8 years, respectively. PLWH had significantly higher prevalence of elevated inflammatory biomarkers compared with HIV-negative individuals even after adjustment for traditional CVD risk factors. Compared with individuals without HIV, the prevalence of elevated biomarkers was highest among persons with detectable viral load and CD4 T-cell counts 200 cells/μl or less. In a subanalysis among PLWH, nadir CD4 T-cell count 200 cells/μl or less was associated with elevated soluble CD14 (sCD14); dyslipidemia with elevated sCD14, sICAM-1, and sVCAM-1; and overweight/obesity with reduced sCD14. Longer ART exposure (>4 years) was associated with reduced sVCAM-1 and sICAM-1.
Conclusion: HIV and not traditional CVD risk factors is a primary contributor of monocyte/macrophage activation and inflammation despite ART. Anti-inflammatory therapies in addition to ART may be necessary to reduce these immune dysregulations and improve health outcomes of African PLWH.
The ATDC5 cell line exhibits a multistep process of chondrogenic differentiation analogous to that observed during endochondral bone formation. Previous investigators have induced ATDC5 cells to differentiate by exposing them to insulin at high concentrations. We have observed spontaneous differentiation of ATDC5 cells maintained in ascorbic acid-containing alpha-MEM. A comparison of the differentiation events in response to high-dose insulin vs. ascorbic acid showed similar expression patterns of key genes, including collagen II, Runx2, Sox9, Indian hedgehog, and collagen X. We took advantage of the action of ascorbic acid to examine signaling events associated with differentiation. In contrast to high-dose insulin, which downregulates both IGF-I and insulin receptors, there were only minimal changes in the abundance of these receptors during ascorbic acid-induced differentiation. Furthermore, ascorbic acid exposure was associated with ERK activation, and ERK inhibition attenuated ascorbic acid-induced differentiation. This was in contrast to the inhibitory effect of ERK activation during IGF-I-induced differentiation. Inhibition of collagen formation with a proline analog markedly attenuated the differentiating effect of ascorbic acid on ATDC5 cells. When plates were conditioned with ATDC5 cells exposed to ascorbic acid, ATDC5 cells were able to differentiate in the absence of ascorbic acid. Our results indicate that matrix formation early in the differentiation process is essential for ascorbic acid-induced ATDC5 differentiation. We conclude that ascorbic acid can promote the differentiation of ATDC5 cells by promoting the formation of collagenous matrix and that matrix formation mediates activation of the ERK signaling pathway, which promotes the differentiation program.
BACKGROUND:Traditional cardiovascular disease (CVD) risk factors contribute to increase risk of CVD in people living with HIV (PLWH). Of all world regions, sub-Saharan Africa has the highest prevalence of HIV yet little is known about PLWH's CVD knowledge and self- perceived risk for coronary heart disease (CHD). In this study, we assessed PLWH's knowledge, perception and attitude towards cardiovascular diseases and their prevention. METHODS:We conducted a cross-sectional study in the largest HIV care program in western Kenya. Trained research assistants used validated questionnaires to assess CVD risk patterns. We used logistic regression analysis to identify associations between knowledge with demographic variables, HIV disease characteristics, and individuals CVD risk patterns. RESULTS:There were 300 participants in the study; median age (IQR) was 40 (33-46) years and 64 % women. The prevalence of dyslipidemia, overweight and obesity were 70 %, 33 % and 8 %, respectively. Participant's knowledge of risk factors was low with a mean (SD) score of 1.3 (1.3) out of possible 10. Most (77.7 %) could not identify any warning signs for heart attack. Higher education was a strong predictor of CVD risk knowledge (6.72, 95 % CI 1.98-22.84, P < 0.0001). Self-risk perception towards CHD was low (31 %) and majority had inappropriate attitude towards CVD risk reduction. CONCLUSION:Despite a high burden of cardiovascular risk factors, PLWH in Kenya lack CVD knowledge and do not perceived themselves at risk for CHD. These results emphasis the need for behavior changes interventions to address the stigma and promote positive health behaviors among the high risk HIV population in Kenya.
BACKGROUND:Acute coronary syndrome (ACS) is understudied in sub-Saharan Africa despite its increasing disease burden. We sought to create an ACS registry at Kenyatta National Hospital to evaluate the presentation, management and outcomes of ACS patients. METHODS:From November 2016 to April 2017, we conducted a retrospective review of ACS cases managed at Kenyatta National Hospital between 2013 and 2016, with a primary discharge diagnosis of ACS, based on International Classification of Diseases (ICD) 10 coding (I20-I24). We compared the presentation, management and outcomes by ACS subtype using analysis of variance testing. We created multivariable logistic regression models using the Global Registry of Acute Coronary Events (GRACE) risk score to evaluate the association between clinical variables, including guideline-directed medical therapy and in-hospital outcomes. RESULTS:Among 196 ACS admissions, the majority (65%) was male, and the median age was 58 years. Most (57%) ACS admissions were for ST-segment-elevation myocardial infarction (STEMI). In-hospital dual antiplatelet (> 85%), beta-blockade (72%) and anticoagulant (72%) therapy was common. A minority (33%) of patients with STEMI was eligible for reperfusion therapy but only 5% received reperfusion. In-hospital mortality rate was 17%, and highest among individuals presenting with STEMI (21%). After multivariable adjustment, higher serum creatinine level was associated with higher odds of in-hospital death (OR = 1.84, 95% CI: 1.21 - 2.78), and STEMI and Killip class > 1 were associated with in-hospital composite of death, re-infarction, stroke, major bleeding or cardiac arrest (STEMI: OR = 8.70, 95% CI: 2.52 - 29.93; Killip > 1: OR = 10.7, 95% CI: 3.34-34.6). CONCLUSIONS:We describe the largest ACS registry at Kenyatta National Hospital to date and identify potential areas for improved ACS care related to diagnostics and management to optimise in-hospital outcomes.
Atrial fibrillation (AF) is a major contributor to the global cardiovascular disease burden. The clinical profile and outcomes of AF patients with valvular heart diseases in sub-Saharan Africa (SSA) have not been adequately described. We assessed clinical features and 12-month outcomes of patients with valvular AF (vAF) in comparison to AF patients without valvular heart disease (nvAF) in western Kenya.We performed a cohort study with retrospective data gathering to characterize risk factors and prospective data collection to characterize their hospitalization, stroke and mortality rates.The AF patients included 77 with vAF and 69 with nvAF. The mean (SD) age of vAF and nvAF patients were 37.9(14.5) and 69.4(12.3) years, respectively. There were significant differences (p<0.001) between vAF and nvAF patients with respect to female sex (78% vs. 55%), rates of hypertension (29% vs. 73%) and heart failure (10% vs. 49%). vAF patients were more likely to be taking anticoagulation therapy compared to those with nvAF (97% vs. 76%; p<0.01). After 12-months of follow-up, the overall mortality, hospitalization and stroke rates for vAF patients were high, at 10%, 34% and 5% respectively, and were similar to the rates in the nvAF patients (15%, 36%, and 5%, respectively).Despite younger age and few comorbid conditions, patients with vAF in this developing country setting are at high risk for nonfatal and fatal outcomes, and are in need of interventions to improve short and long-term outcomes.
Project Title
Inflammation, T Cell activation and Subclinical atherosclerosis in Treated HIV Infection (Kenya CVHIV)
EDCTP Project
TMA2016CDF1598
EDCTP Program
EDCTP2
EDCTP Project Call
Career Development Fellowship (CDF)
Host Organisation
| Department | Institution | Country |
|---|---|---|
| University of Nairobi | University of Nairobi | KE |
Project Objectives
SPECIFIC AIMS In sub-Saharan Africa, more than 25 million people live with HIV/AIDS, cardiovascular disease (CVD) is a leading cause of morbidity and mortality1. HIV infection has been shown to increase risk of CVD in European and US populations, raising concerns that the HIV epidemic will significantly accelerate rates of CVD in Africa as the HIV-infected population lives longer and there are fewer deaths from HIV-related causes2-4. In Kenya and other countries hard hit by the HIV epidemic, there is an urgent need to expand our understanding of CVD epidemiology and risk factors. Without this, it will be impossible to garner national and international support needed to adopt and implement guidelines, programs and policies to reduce CVD risk at the population level. As in resource-rich countries, traditional CVD risk factors are highly prevalent among HIV-infected adults in sub-Saharan Africa. More than 55% of HIV-infected adults on antiretroviral therapy (ART) in one Ugandan study were found to have metabolic syndrome, defined as having at least two of the following: hypertension; fasting blood glucose, hyperlipidemia; high BMI5,6. HIV-specific risk factors are also likely to play an important role through inflammation and immune activation7. The relative contribution of immune activation and inflammation is not well defined in Africa and is one of the questions to be addressed in this application. While many developed country based studies find an association between inflammation and subclinical atherosclerosis8, this has not been the case in the more limited number of African studies. Furthermore, compared to US and Europe studies, studies in sub-Saharan Africa have been small, have not directly evaluated the contribution of risk due to inflammation/immune activation, and have not compared HIV-infected and uninfected adults9-11. This latter comparison may be particularly relevant in regions such as western Kenya where all adults regardless of HIV status
Study Design
Study Design and Methods Relevant to Specific Aims 1 Specific Aim 1a: To determine if high sensitivity C-reactive protein serum levels, and other inflammation biomarkers are significantly higher in HIV positive compared to the HIV negative subjects. Specific Aim 1b: To determine if the percentage of CD38+ and HLA-DR+ CD8+ T cells and other markers of cellular immune activation including CMV-specific T cell responses are significantly higher among HIV-infected compared to uninfected controls. Rationale: In resource-rich setting, persistent immune activation and inflammation has been observed even in virally suppressed and has been associated with subclinical atherosclerosis. There is considerable controversy regarding the inflammatory state of HIV-infected patients in Africa particularly western Kenya where all adults regardless of HIV status are at risk for inflammation and immune activation due to chronic exposure to bacterial and parasitic infections, including malaria and helminthes. Therefore, identifying important differences in inflammation and immune activation biomarkers between those with and without HIV infection will be essential to tailoring future public health and treatment interventions. Using the facilities and resources of the University of Nairobi College of Health Sciences Medical Microbiology laboratory, I propose to use banked samples from Kenya CVHIV study to measure levels of inflammatory and immune activation markers of 200 HIV-infected individuals on long term ART treatment and 100 age/match uninfected controls to determine if HIV positive patients have increased inflammation and immune activation. The primary endpoint for Aim 1a and 1b will be high
Project Summary
Despite the high prevalence of HIV in sub-Saharan Africa, Cardiovascular diseases (CVD) are the leading causes of morbidity and mortality in this region. Predictors of CVD are well established in resource-rich countries, but whether these same risk factors are strongly associated with CVD in sub-Saharan Africa is not known. Growing evidence from Europe suggests that HIV itself may be a risk factor for CVD, through a combination of medication side effects, inflammation and immune activation, but how HIV disease and treatment impacts CVD risk in Kenya and other countries with generalized HIV epidemics is less well studied. In addition, it remains unclear whether inflammation and immune activation truly predicts early risk of CVD in African HIV-infected subjects and should remain a target for intervention. The goal of this project is to assess the relative contributions of persistent inflammation and immune activation in subliclinical atherosclerosis in HIV-infected subjects. Our central hypothesis is that systemic immune activation and inflammation associated with HIV infection contribute to early risk of CVD in HIV positive individuals, and that CMV infection and microbial translocation may contribute to this process. Aim 1: To determine if HIV-infected individuals have increased inflammation and immune activation compare to the uninfected controls, Aim 2: To test the markers of immune activation and inflammation are associated with an increased risk of subclinical atherosclerosis. Aims 1&2 will leverage the ongoing Kenya study of cardiovascular diseases during HIV infection cohort of 300 HIV-infected on long-term antiretroviral treatment and 300 HIV-uninfected subjects. We will conduct a cross-sectional, nested case-control study of 200 HIV+ and 100 HIV- subjects and analyze banked blood from the study for markers of inflammation, CMV infection, microbial translocation and cellular immune activation, selected for their association with CVDs in HIV- uninfected populations. We will investigate associations with subclinical atherosclerosis in HIV+, adjusting for age, sex, HIV related and traditional risk factors and derive a set of candidate biomarkers to validate prospectively. This innovative and important clinical study on a well characterized cohort will illuminate the mechanisms leading to increased risk of CVD in HIV-infected individuals and provide data that will be critical to developing targeted, feasible intervention trials to combat CVD in sub-Saharan Africa over the next decade. It would provide a springboard for launching Dr. Temu's independent physician-scientist career in the field of HIV immunology in Kenya.