Kenyan Patients Research Articles

HIV-1 subtype diversity based on envelope C2V3 sequences from Kenyan patients on highly active antiretroviral therapy.

There is a continuous need to genetically characterize the HIV strains in circulation in order to assess interventions and inform vaccine discovery. We partially sequenced the envelope C2V3 gene from a total of 59 Kenyan patients on highly active antiretroviral treatment (HAART) and determined HIV subtypes using both the JPHMM subtyping tool and the phylogenetic method. HIV-1 subtype A1 was the predominant strain in circulation, representing 65.5% and 74.5% of all isolates as determined by JPHMM and phylogenetic methods, respectively. Subtypes C and D were the next most prevalent pure strains at 9.1% each by both methods. JPHMM identified 9.1% of the isolates as recombinant. Four isolates had short sequences not covering the entire C2V3 region and were thus not subtyped. From this study, subtype A viruses are still the predominant HIV-1 strains in local circulation in Kenya. Constant surveillance is needed to update molecular trends under continuing HAART scale-up.

Abstract B35: Cumulative results from an investigation of transcriptome differences in breast cancer samples from African American and East African triple-negative breast cancer patients

Abstract We report our cumulative results of a multi-year study focusing on the genomic similarities and differences between Triple-negative breast cancer (TNBC) in native African and U.S. African patients. We used a cohort of African-American (AA) TNBC patients from South Florida and an indigenous cohort of Kenyan TNBC patients. Strong U.S. epidemiological data supports breast cancer (BC) as the second leading cause of cancer death among AA women, with a 20% greater mortality rate than that in Caucasian-American women (CA). AA women often present with tumors that are of higher grade and later stage and their relapse-free and overall survival period is significantly lower than CA. Additionally, TNBC has a higher prevalence in AA women. All of these observations lead to a much poorer prognosis for AA BC patients- thus defining the all-encompassing term “disparities in BC in women of African ancestry”. In our study, we used archived formalin fixed paraffin embedded (FFPE) blocks, collected across a stage-matched multi-ethnic U.S. cohort of node-negative TNBC from the University of Miami and similar TNBC samples from the Kijabe Hospital (Kenya). Using 10 μm scrolls from each block, total RNA was isolated, cDNA prepared, and hybridized to a breast cancer enriched gene expression array (Affymetrix Platform BC DSA Research Tool) in collaboration with Almac Diagnostics. Gene expression analysis was conducted using GeneSpring 12.1® analytical software. The raw data, a total of 60,856 gene/probes, was pre-processed using Robust MultiArray Average (RMA) algorithm; background corrected, log2 transformed to the baseline median of all samples and then quintile normalized. The samples that passed final QC were then filtered to remove low-intensity signals (< 20% signal). The final analysis cohort consisted of 10-AA, 13-CA and 21-Kenyan. PCA analysis revealed that the samples clustered well with respect to ethnicity. Unsupervised cluster analysis, based on ethnicity and genes (p value <.05, fold change >2.5), was performed. The resulting dendogram clearly segregated into distinct subgroups based on ethnicity, revealing a pattern of differential gene expression between the cohorts. A list of differentially expressed genes from each cohort (DEG) were selected using ANOVA analysis (fold change > 3.0, p value <.05) followed by the Benjamin and Hochberg method for multiple-testing correction. Finally, the lists of DEG were uploaded into GeneGo MetaCore to identify functionally enriched pathways. These analyses revealed significantly deregulated genes associated with the Wnt/β-catenin pathway in the AA cohort, as compared to the CA, suggesting that this pathway may contribute to the more aggressive phenotype in AA women diagnosed with TNBC. Additionally, significantly deregulated genes associated with the Oncostatin M pathway were discovered in the Kenyan cohort, as compared to the AA and CA tumors. In particular, STAT1 was significantly downregulated in the Kenyan cohort compared to the CA and AA. Thus, our results indicate gene expression differences within several key pathways across these ethnic groups. In summary, this study represents the first direct comparison of gene expression in TNBC specimens across U.S. CA and AA BC patients and Kenyan East Africans. These studies have important implications for further understanding BC ethnic disparities, as well as tailored approaches to prediction, prevention and therapeutic measures. Citation Format: Julie E. Getz, Mary E. Ahearn, Carmen Gomez, Biju Issac, Jennifer Clarke, Mark D. Pegram, Peter Bird, John D. Carpten, Lisa L. Baumbach. Cumulative results from an investigation of transcriptome differences in breast cancer samples from African American and East African triple-negative breast cancer patients. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B35. doi:10.1158/1538-7755.DISP13-B35

High prevalence of Rickettsia africae variants in Amblyomma variegatum ticks from domestic mammals in rural western Kenya: implications for human health.

Tick-borne spotted fever group (SFG) rickettsioses are emerging human diseases caused by obligate intracellular Gram-negative bacteria of the genus Rickettsia. Despite being important causes of systemic febrile illnesses in travelers returning from sub-Saharan Africa, little is known about the reservoir hosts of these pathogens. We conducted surveys for rickettsiae in domestic animals and ticks in a rural setting in western Kenya. Of the 100 serum specimens tested from each species of domestic ruminant 43% of goats, 23% of sheep, and 1% of cattle had immunoglobulin G (IgG) antibodies to the SFG rickettsiae. None of these sera were positive for IgG against typhus group rickettsiae. We detected Rickettsia africae-genotype DNA in 92.6% of adult Amblyomma variegatum ticks collected from domestic ruminants, but found no evidence of the pathogen in blood specimens from cattle, goats, or sheep. Sequencing of a subset of 21 rickettsia-positive ticks revealed R. africae variants in 95.2% (20/21) of ticks tested. Our findings show a high prevalence of R. africae variants in A. variegatum ticks in western Kenya, which may represent a low disease risk for humans. This may provide a possible explanation for the lack of African tick-bite fever cases among febrile patients in Kenya.

Correlates of Adherence and Antiretroviral Treatment Failure in HIV-1 Infected Kenyan Patients

Correlates of Adherence and Antiretroviral Treatment Failure in HIV-1 Infected Kenyan Patients

Abstract 3851: Molecular profiling of aggressive breast cancer in a unique patient population from Kenya

Abstract Breast cancer rates of incidence and mortality vary significantly between different nations and racial groups. African nations have the highest breast cancer mortality rates in the world, even though the incidence rates are below those of many other nations. In Kenya, breast cancer tumors are often highly aggressive at presentation and occur at a significantly earlier age (as early as the teens and 20s), relative to North American women. In the United States, non-Hispanic white women have the highest incidence of breast cancer, but African-American women have the highest mortality. These striking racial disparities are due not only to inequities in screening and treatment but also to variations in the rates of aggressive breast cancer. Differences in disease progression suggest that aggressive breast cancer tumors may harbor components of a unique molecular signature that result in racial disparities. We aim to identify drivers of poor prognosis breast cancer growth by identifying molecular signatures with high prognostic value from tumor samples of patients with aggressive disease. We hypothesize that changes in the DNA, RNA, and post-translational protein regulation contribute to aggressive disease. To characterize the tumors from this patient population, we used samples from >100 Kenyan breast tumor tissue samples. We stained tissue microarray sections for clinical breast cancer markers including lymphocyte markers. Using DNA and RNA that we isolated from these patient-derived breast tumors, we are characterizing these tumors by analyzing them for gene expression, genome sequencing, proteomics, and pathology analysis coupled with bioinformatics to develop signatures of aggressive breast cancer growth and metastasis. Our data will be foundational in understanding how aggressive, lethal breast tumors of Kenyan breast cancer patients differ from less aggressive tumors and will enhance our ability to diagnose and eliminate outcome disparities in breast cancer patients. Citation Format: Rispah Torrorey, Maggie Kerper, Emilia Hartland, Zonggao Shi, Jenifer Prosperi, Sunil Badve, Sharon Stack, Simeon Mining, Laurie Littlepage. Molecular profiling of aggressive breast cancer in a unique patient population from Kenya. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3851. doi:10.1158/1538-7445.AM2014-3851

Does the length of specimen storage affect influenza testing results by real-time reverse transcription-polymerase chain reaction? An analysis of influenza surveillance specimens, 2008 to 2010

In some influenza surveillance systems, timely transport to laboratories for reverse transcription-polymerase chain reaction (RT-PCR) testing is challenging.Guidelines suggest that samples can be stored at 4°Cfor up to 96 hours but the effect of longer storage times has not been systematically evaluated. We collected nasopharyngeal and oropharyngeal specimens from patients in Kenya and stored them in viral transport medium at 2 to 8°C before testing for influenza A and B using real-time RT-PCR. From April 2008 to November 2010, we collected 7,833 samples; 940 (12%) were positive for influenza. In multivariable analysis, specimens stored for six days were less likely to be influenza-positive compared to specimens stored between zero and one day (adjusted odds ratio (a OR): 0.49, 95%confidence interval (CI): 0.27–0.93). There was no statistically significant difference in influenza positivity of specimens stored for five days compared to zero to one day. There was no statistically significant relationship between days in refrigeration and cycle threshold(Ct) values for positive samples (p=0.31). We found that samples could remain in storage for at least five days without affecting the proportion-positive of samples,potentially increasing the feasibility of including influenza surveillance sites in remote areas.

Pharmacokinetics (Pk) of Oral Etoposide (Oe) in Kenyans with Hiv-Related Kaposi'S Sarcoma (Ks) on Anti-Retroviral Therapy (Art)

ABSTRACT Aim: Recent trials in SSA have shown OE is effective for palliation of KS symptoms, in patients without access to ART. OE PK exhibit high intersubject variability, and the dose-limiting side effect of OE, neutropenia, is related to etoposide exposure. The clinical risk of neutropenia is significantly higher in resource-limited settings, where access to supportive care may be limited. To date, the PK of OE in SSA populations has not been described; therefore the safety of OE is poorly defined. This trial describes first-dose PK of OE in Kenyan patients with HIV-related KS on ART. Methods: This clinical trial was IRB approved. HIV-positive adults (≥18 yo) with biopsy-proven KS, without prior KS therapy, but on ART were eligible for participation. Following informed consent, patients were given 50 mg oral etoposide (IV formulation), with collection of dried blood spots for subsequent PK analysis at pre-dose, 1, 2, 4, 6, and 8 hours post-dose. Following liquid extraction of the dried blood spots, etoposide concentrations were measured using a validated HPLC-MS/MS assay with teniposide as internal standard. Non-compartmental PK analysis was performed using the linear trapezoidal rule in MS-Excel. Results: 29 subjects participated in this clinical trial. Day 1 PK parameters are presented. Patients were on several different ART regimens, although none were on ritonavir, a known strong inhibitor of etoposide metabolism. PK Parameters of OE PK Parameter Mean Coefficient of Variation (CV%) Range Cmax (ng/mL) 611.7 36 114-1001 Tmax (h) 1.2 35 874-14760 AUC (0-inf) (ng/L.h) 3998 70 874-14760 CL/F (L/h) 18.25 64 3.39-57.21 Vd (L) 107 69 50-420 Conclusions: This study is the first to describe the PK of OE in Kenyans with HIV-associated KS on ART. While OE has exhibited high intersubject variability in prior studies, this study showed higher variability than previously reported: CV% in prior reports has generally been less than 50%, and in the present study is 60-70%. Ongoing analysis is exploring the role, if any, of body composition, co-medications, and genetics on the described PK variability. This preliminary data demonstrates that OE in a SSA population exhibits high intersubject variability, and therefore to ensure safety in this population, further study is needed of etoposide kinetics. Disclosure: All authors have declared no conflicts of interest.

Palliative care-related self-report problems among cancer patients in East Africa: a two-country study.

Palliative care-related problems have not been measured in Africa in line with the WHO definition. This study aimed to measure the three-day period intensity of multidimensional problems (physical, psychological, social, and spiritual) among advanced cancer patients in Kenya and Uganda. Adults with advanced malignant disease gave self-report data to the African Palliative Outcome Scale (POS). Among 210 respondents, more than half had an underlying HIV diagnosis (51.9 %). The worst ranked POS items were pain and information. In three multivariable ordinal logistic regression models with the 3 POS factors as dependent variables, for the first model (factor 1 physical and psychological well-being), as age increased, the well-being also improved (B = 0.022, p = 0.037), and as physical function score worsened, factor score also worsened (B = -0.685, p < 0.001). In the second model (factor 2 interpersonal well-being), a trend toward significance was found for gender, with being male predicting a higher (better) factor score (B = 0.502, p = 0.067). For the third model (factor 3 existential and spiritual), increasing age was predictive of higher (better) factor score (B = 0.023, p = 0.032), and worsening function was predictive of lower (worse) factor score (B = -0.543, p < 0.001). This novel data revealed pain and information to plan for the future to affect patients most severely, underlining the importance of analgesia and social support. HIV infection did not affect the level of need. Our data suggest increasing need as function declines; therefore, home-based models with adequate family support are essential.

Cryptosporidiosis in HIV/AIDS patients in Kenya: clinical features, epidemiology, molecular characterization and antibody responses.

We investigated the epidemiological and clinical features of cryptosporidiosis, the molecular characteristics of infecting species and serum antibody responses to three Cryptosporidium-specific antigens in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients in Kenya. Cryptosporidium was the most prevalent enteric pathogen and was identified in 56 of 164 (34%) of HIV/AIDS patients, including 25 of 70 (36%) with diarrhea and 31 of 94 (33%) without diarrhea. Diarrhea in patients exclusively infected with Cryptosporidium was significantly associated with the number of children per household, contact with animals, and water treatment. Cryptosporidium hominis was the most prevalent species and the most prevalent subtype family was Ib. Patients without diarrhea had significantly higher serum IgG levels to Chgp15, Chgp40 and Cp23, and higher fecal IgA levels to Chgp15 and Chgp40 than those with diarrhea suggesting that antibody responses to these antigens may be associated with protection from diarrhea and supporting further investigation of these antigens as vaccine candidates.

Blood pressure level impacts risk of death among HIV seropositive adults in Kenya: a retrospective analysis of electronic health records.

BackgroundMortality among people with human immunodeficiency virus (HIV) infection is increasingly due to non-communicable causes. This has been observed mostly in developed countries and the routine care of HIV infected individuals has now expanded to include attention to cardiovascular risk factors. Cardiovascular risk factors such as high blood pressure are often overlooked among HIV seropositive (+) individuals in sub-Saharan Africa. We aimed to determine the effect of blood pressure on mortality among HIV+ adults in Kenya.MethodsWe performed a retrospective analysis of electronic medical records of a large HIV treatment program in western Kenya between 2005 and 2010. All included individuals were HIV+. We excluded participants with AIDS, who were <16 or >80 years old, or had data out of acceptable ranges. Missing data for key covariates was addressed by inverse probability weighting. Primary outcome measures were crude mortality rate and mortality hazard ratio (HR) using Cox proportional hazards models adjusted for potential confounders including HIV stage.ResultsThere were 49,475 (74% women) HIV+ individuals who met inclusion and exclusion criteria. Mortality rates for men and women were 3.8 and 1.8/100 person-years, respectively, and highest among those with the lowest blood pressures. Low blood pressure was associated with the highest mortality incidence rate (IR) (systolic <100 mmHg IR 5.2 [4.8-5.7]; diastolic <60 mmHg IR 9.2 [8.3-10.2]). Mortality rate among men with high systolic blood pressure without advanced HIV (3.0, 95% CI: 1.6-5.5) was higher than men with normal systolic blood pressure (1.1, 95% CI: 0.7-1.7). In weighted proportional hazards regression models, men without advanced HIV disease and systolic blood pressure ≥140 mmHg carried a higher mortality risk than normotensive men (HR: 2.39, 95% CI: 0.94-6.08).ConclusionsAlthough there has been little attention paid to high blood pressure among HIV+ Africans, we show that blood pressure level among HIV+ patients in Kenya is related to mortality. Low blood pressure carries the highest mortality risk. High systolic blood pressure is associated with mortality among patients whose disease is not advanced. Further investigation is needed into the cause of death for such patients.

PIN86 - Determinants Of Quality Of Life In Newly Diagnosed Hiv Infected Patients In Kenya

PIN86 - Determinants Of Quality Of Life In Newly Diagnosed Hiv Infected Patients In Kenya

Physician communication behaviors from the perspective of adult HIV patients in Kenya

We describe perceived physician communication behaviors and its association with adherence to care, among HIV patients in Kenya. This cross-sectional study was conducted between July and August 2011. The study was conducted in three adult HIV clinics within the Academic Model Providing Healthcare program in western Kenya. HIV adult patients. Patient's predisposition to attend clinic, missed appointment and missed combined antiretroviral therapy (cART) medication. A total of 400 patients were enrolled and participated in the study; the median age was 38 years (IQR = 33-44) and 56.5% were female. Patients perceived physicians engaged in a high number of communication behaviors (mean = 3.80, range 1-5). A higher perceived general health status (P = 0.01), shorter distance to the health facility (P = 0.03) and lesser time spent at the health facility (P = 0.02) were associated with a higher number of perceived physician communication behaviors. Physician-patient relationship factors were not associated with physician communication behaviors. In addition, a higher number of perceived physician communication behaviors was associated with a very high likelihood of patients' attending the next HIV clinic [adjusted odds ratio (AOR): 1.89, 95% confidence interval (CI): 1.49-2.40], a lower likelihood of patients' missing an appointment (AOR: 0.75, 95% CI: 0.61-0.92) and missing cART medication (AOR: 0.68, 95% CI: 0.52-0.87). Patients' perception of physician communication behaviors was found to be associated with their adherence to HIV care.

Occurrence of etravirine/rilpivirine-specific resistance mutations selected by efavirenz and nevirapine in Kenyan patients with non-B HIV-1 subtypes failing antiretroviral therapy

Resistance to efavirenz and nevirapine has not been associated with mutations at position 138 of reverse transcriptase. In an evaluation of virologic suppression rates in PEPFAR (President's Emergency Plan For AIDS Relief) clinics in Kenya among patients on first-line therapy (RV288), 63% (617/975) of randomly selected patients on antiretroviral therapy were suppressed (HIV RNA<400 copies/ml). Among those with non-nucleoside reverse transcriptase inhibitor resistance (n = 101), 14 (13.8%) had substitutions at 138 (A, G, K or Q), mutations selected only by etravirine and rilpivirine in subtype B viruses. All 14 patients received efavirenz or nevirapine, not etravirine or rilpivirine, and were predominantly subtype A1. This may be the first report of efavirenz and nevirapine selecting these mutations in these subtypes.

Naturally occurring protease inhibitor resistance mutations and their frequencies in HIV proviral sequences of drug-naïve sex workers in Nairobi, Kenya

Sub-Saharan Africa accounts for 69% of the people living with HIV globally. An estimated 1,600,000 Kenyans are living with HIV-1. Antiretroviral therapy (ART) has saved 9 million life-years in Sub-Saharan Africa. However, drug resistance mutations reduce the effectiveness of ART, and need to be monitored for effective ART. Naturally occurring primary antiretroviral drug resistance mutations have not been well analyzed in ART naive HIV+ patients in Kenya. Here we have examined protease inhibitor (PI) resistance mutations in ART naive HIV-1 seropositive women in Pumwani sex worker cohort established in Nairobi, Kenya, wherein HIV-1 infection is predominantly caused by subtypes A and D viruses. We have analyzed consensus sequences of HIV protease from 109 drug-naive patients, as a part of HIV-1 whole-genome sequencing using 454 sequencing methodology. Analysis using HIVdb program revealed a prevalence of 22% (24/109) PI resistance mutations among the study subjects. D30N (3.7%), M46I (0.9%) and V82F (0.9%) are the major mutations observed. D30N mutation is known to confer high-level resistance to nelfinavir. M46I and V82F confer resistance to indinavir, lopinavir, fosamprenavir and nelfinavir. In addition, many minor mutations were found at seven different drug resistance sites. It is important to study the implications of these mutations to the effectiveness of specific PI drug treatment. This study provides valuable data pertaining to primary drug resistance in Kenyan HIV-1 infected patients before ART became available.

Analysis of factors contributing to the low survival of cervical cancer patients undergoing radiotherapy in Kenya.

BackgroundIn contrast to the developed nations, invasive cervical cancer (ICC) is the most common womens malignancy in Kenya and many other locations in sub-Saharan Africa. However, studies on survival from this disease in this area of the world are severely restricted by lack of patient follow-up. We now report a prospective cohort study of ICC in Kenyan women analysing factors affecting tumour response and overall survival in patients undergoing radiotherapy.Methods and FindingsBetween 2008 and 2010, 355 patients with histologically confirmed ICC were recruited at the Departments of Gynaecology and Radiotherapy at Kenyatta National Hospital (KNH). Structured questionnaires were completed recording socio-demographics, tumour response and overall survival following treatment with combinations of external beam radiation (EBRT), brachytherapy and adjuvant chemotherapy. Of the 355 patients, 42% (146) were lost to follow-up while 18% (64) died during the two year period. 80.5% of patients presented with advanced stage IIB disease or above, with only 6.7% of patients receiving optimal combined EBRT, brachytherapy and adjuvant chemotherapy. Kaplan Meier survival curves projected two year survival at <20%.ConclusionCervical cancer is preventable yet poverty, poor education, lack of cancer awareness coupled with an absence of regular screening programs, late patient presentation, sub-optimal diagnosis and treatments are major factors contributing to the alarmingly low survival rate of cervical cancer patients in Kenya. It is concluded that simple cost-effective changes in clinical practice could be introduced which would have a marked impact on patient survival in this setting.

Cognitive malfunction impairment and stigma in HIV/AIDS epileptic patients in Kenya

Cognitive malfunction impairment and stigma in HIV/AIDS epileptic patients in Kenya

Prevalence and Correlates of Pain and Pain Treatment in a Western Kenya Referral Hospital

Pain is often inadequately evaluated and treated in sub-Saharan Africa (SSA). We sought to assess pain levels and pain treatment in 400 hospitalized patients at a national referral hospital in western Kenya, and to identify factors associated with pain and pain treatment. Using face-validated Kiswahili versions of two single-item pain assessment tools, the Numerical Rating Scale (NRS) and the Faces Pain Scale-Revised (FPS-R), we determined patients' pain levels. Additional data collected included patient demographics, prescribed analgesics, and administered analgesics. We calculated mean pain ratings and pain management index (PMI) scores. Averaged between the NRS and FPS-R, 80.5% of patients endorsed a nonzero level of pain and 30% of patients reported moderate to severe pain. Older patients, patients with HIV, and cancer patients had higher pain ratings. Sixty-six percent of patients had been prescribed analgesics at some point during their hospitalization, the majority of which were nonopioids. A majority of patients (66%) had undertreated pain (negative scores on the PMI). This study shows that hospitalized patients in Kenya are experiencing pain and that this pain is often undertreated.

Infectious diarrhoea in antiretroviral therapy-naive HIV/AIDS patients in Kenya

Diarrhoea is a significant cause of morbidity and mortality in immunocompromised patients. The objectives of this study were to investigate the aetiological agents, risk factors and clinical features associated with diarrhoea in HIV/AIDS patients in Kenya. Sociodemographic, epidemiological and clinical data were obtained for 164 HIV/AIDS patients (70 with and 94 without diarrhoea) recruited from Kenyatta National Hospital, Kenya. Stool samples were examined for enteric pathogens by microscopy and bacteriology. Intestinal protozoa and fungi were identified in 70% of patients, more frequently in those with diarrhoea (p<0.001). Helminths were detected in 25.6% of patients overall, and bacterial pathogens were identified in 51% of patients with diarrhoea. Polyparasitism was more common in patients with diarrhoea than those without (p<0.0001). Higher CD4(+) T-cell count (OR = 0.995, 95% CI 0.992-0.998) and water treatment (OR = 0.231, 95% CI 0.126-0.830) were associated with a lower risk of diarrhoea, while close contact with cows (OR = 3.200, 95% CI 1.26-8.13) or pigs (OR = 11.176, 95% CI 3.76-43.56) were associated with a higher risk of diarrhoea. Multiple enteric pathogens that are causative agents of diarrhoea were isolated from stools of antiretroviral therapy-naïve HIV/AIDS patients, indicating a need for surveillance, treatment and promotion of hygienic practices.

Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya

Hepatitis B virus (HBV) genotypes are important in both the clinical manifestation of disease and treatment response. Although Kenya belongs to the African Region (AFR-E) characterized by high mortality and hyperendemicity of HBV, there is a paucity of HBV genotyping data. The aim of this study was to molecularly characterize the basic core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolated from 61 HBsAg-positive liver disease patients attending Kenyatta National Hospital in Nairobi. HBsAg, HBeAg and viral loads were determined. HBV DNA was amplified and sequenced from 58/61 patients. In addition to the complete genome of two isolates, the BCP/PC and the complete S regions of 43 and 38 isolates, respectively were sequenced. Following phylogenetic analysis of the S region, 38 isolates clustered with subgenotype A1, whereas two isolates clustered with genotype D, one with subgenotype D1 and another as an outlier of the clade containing subgenotype D6 and the D/E recombinant. When the complete genome of the latter isolate was sequenced it clustered with D6. The majority of isolates belonged to serological subtype adw2 and only four to ayw2. Three distinct groups of subgenotype A1, distinguished by different amino acid motifs, circulate in Kenya: two in the African cluster and a monophyletic clade in the “Asian” cluster. HBeAg-negativity was a result of G1896A in genotype D isolates, whereas in subgenotype A1, the HBeAg-negativity was a result of mutations in the Kozak region (1809–1812) or precore start codon (1814–1816). Mutations at positions 1762 and 1764 occurred more frequently in HCC patients (p<0.05). In conclusion, subgenotypes A1, D1 and D6 circulate in liver disease patients in Kenya, with A1 predominating.

Profile of HIV Type 1 Coreceptor Tropism Among Kenyan Patients from 2009 to 2010

A switch of HIV coreceptor usage from CCR5 to CXCR4 occurs in AIDS pathogenesis and may play a critical role in the use of entry inhibitors. To determine the potential usefulness of maraviroc and other CCR5 antagonists among drug-naive and experienced patients in Kenya, the env-C2-V3 gene was successfully sequenced in samples from 176 (98 men and 78 female) consenting subjects between January 2009 and December 2012. In silico CPSSM, webPSSM/, and (ds) Kernel tools were used in predicting coreceptor usage. On the basis of the env V3 loop sequences, 84.1% (148) were reported with R-5 tropism, 4.5% (5) were dual tropic, while 13.4% (23) were of X4 tropism. However, similar to previous studies conducted in Kenya on genetic diversity, HIV-1 subtype A1 (73.9%; 130/176) still remains the most dominant subtype. The high levels of R5 tropism among the studied Kenyan infected populations suggested the potential use of CCR5 antagonists as new therapeutic options in Kenya.