Margaret Borok

Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi's sarcoma clinical stage.

ObjectiveTo determine the relationship between human herpesvirus 8 (HHV-8 or Kaposis sarcoma-associated herpesvirus) peripheral blood virus load and Kaposis sarcoma (KS) clinical stage. DesignBlinded, cross-sectional analysis of peripheral blood HHV-8 DNA levels in persons with AIDS-related KS in Harare, Zimbabwe. MethodsSubjects were stratified by KS clinical stage. The amount of HHV-8 DNA in plasma and peripheral blood mononuclear cells (PBMC) was determined by quantitative real-time PCR amplification of the HHV-8 open reading frame 26. ResultsThirty-one HIV-1/HHV-8-coinfected persons were studied: 26 subjects had histologically confirmed KS (one stage II, 11 stage III and 14 stage IV) and five subjects had antibodies to HHV-8 but did not have KS. The age, CD4 lymphocyte count and plasma HIV-1 RNA levels were similar in all groups. HHV-8 DNA was detected in the plasma of all HHV-8-infected subjects (range < 2.4 to 5.2 log10 copies/ml), but plasma HHV-8 DNA levels were not associated with KS disease stage. In contrast, the amount of HHV-8 DNA in PBMC (range < 0.7 to 4.5 log10 copies/μg) was strongly associated with KS clinical stage (P = 0.005). Among stage IV KS cases, there was a linear relationship between plasma and PBMC HHV-8 DNA levels (r2 = 0.42;P = 0.01). ConclusionThe strong association observed between the extent of KS disease and the levels of HHV-8 DNA in PBMC provides further evidence for a relationship between HHV-8 virus load and KS pathogenesis.

Evaluation of Plasma Human Herpesvirus 8 DNA as a Marker of Clinical Outcomes during Antiretroviral Therapy for AIDS-Related Kaposi Sarcoma in Zimbabwe

BACKGROUND The usefulness of plasma human herpesvirus 8 (HHV-8) DNA as a marker of response to treatment for acquired immunodeficiency syndrome-associated Kaposi sarcoma (AIDS-KS) in an African setting is unknown. METHODS We conducted a prospective pilot study at the Parirenyatwa Hospital Kaposi Sarcoma Clinic (Harare, Zimbabwe) to investigate the hypothesis that the clinical response of AIDS-KS is associated with suppression of HHV-8 DNA. Antiretroviral therapy (ART) was provided as coformulation of abacavir, lamivudine, and zidovudine. Clinical response was defined as survival to week 96 with either complete or partial resolution of KS disease. RESULTS Ninety ART-naive participants (62 men and 28 women) aged >18 years who had human immunodeficiency virus type 1 (HIV-1) infection and biopsy-confirmed KS were studied; 82% had stage T1 disease. Fifty participants received adjunctive chemotherapy. The median CD4(+) lymphocyte count increased from 124 cells/microL at baseline to 281 cells/microL, the plasma HIV-1 RNA level decreased from 4.69 to <2.60 log(10) copies/mL, the plasma HHV-8 DNA level decreased from 660 to <25 copies/mL, and HHV-8 DNA level in peripheral blood mononuclear cells decreased from 2790 to 37 copies/10(6) cells (P < .001 for each comparison). There were 14 deaths (16%) and 13 patients (15%) lost to follow-up. The most common cause of death was infection. Clinical response of KS occurred in 17 participants (19%). Pretreatment plasma HHV-8 DNA levels of <660 copies/mL were associated with greater survival (odds ratio, 2.83; 95% confidence interval, 1.07-7.53; P = .04) and a better clinical response (odds ratio, 6.38; 95% confidence interval, 1.68-24.19; P = .006). CONCLUSIONS AIDS-KS tumor responses after ART initiation were limited. Pretreatment plasma HHV-8 DNA level may be a surrogate for KS disease that is in need of intensive clinical management.

Gender differences in AIDS-associated Kaposi sarcoma in Harare, Zimbabwe.

Reasons for gender-related differences in the risk of AIDS-related Kaposi sarcoma (AIDS-KS) are unknown. Four hundred thirty-eight male and 166 female AIDS-KS patients were evaluated in Harare, Zimbabwe. Female patients were younger than male patients in this study (median of 33 vs. 38 years; P < 0.001), mirroring the epidemiology of AIDS in Zimbabwe. In a multivariate model adjusted for CD4 T-cell count, age, prior radiation treatment, and chemotherapy, women were more likely to report fever, diaphoresis, or weight loss (odds ratio = 1.7, 95% confidence interval: 1.1 to 2.7; P = 0.009). These findings suggest an increased severity of KS or other unidentified infections among women with AIDS-KS in Zimbabwe.

Lack of evidence for frequent heterosexual transmission of human herpesvirus 8 in Zimbabwe.

BACKGROUND There is conflicting evidence about the contribution of heterosexual transmission to the spread of human herpesvirus 8 (HHV-8) in southern Africa. This study evaluated the hypothesis that HHV-8 infection is associated with risk factors for human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted infections among Zimbabwean men. METHODS HHV-8 seroprevalence was determined for 2750 participants in the Zimbabwe AIDS Prevention Project cohort of male factory workers in Harare, Zimbabwe. Potential associations of HHV-8 antibody detection with risk factors for HIV-1 infection were examined by univariate analysis. Variables with P < .1 in the univariate analysis were included in a multivariate logistic regression model. HHV-8 seroprevalence was also determined among 297 heterosexual couples. RESULTS Prevalence of HHV-8, HIV-1, and HHV-8 and HIV-1 coinfection was 28.5% (95% confidence interval [CI], 26.8%-30.2%), 19.5% (95% CI, 18.0%-20.9%), and 6.5% (95% CI, 5.6%-7.5%), respectively. Detection of HHV-8 antibodies was independently associated with older age and HIV-1 infection but not with number of recent sex partners, marital status, education, condom use, prior sexually transmitted infections, payment for sex, chronic hepatitis B infection, or incident HIV-1 infection. HHV-8 seroprevalence was 31.7% (95% CI, 26.3-37.0) among wives in the couples tested, but HHV-8 infection of wives was not associated with HHV-8 infection of husbands (odds ratio, 1.08; 95% CI, 0.62-1.88; P = .8). CONCLUSIONS HHV-8 and HIV-1 infection did not have common sexual risk factors among urban Zimbabwean men. Sexual transmission does not explain the high prevalence of HHV-8 in this population.

Feasibility and sustainability of an interactive team-based learning method for medical education during a severe faculty shortage in Zimbabwe

BackgroundIn 2010, in the midst of the human immunodeficiency virus (HIV) epidemic in Zimbabwe, 69% of faculty positions in the Department of Medicine of the University of Zimbabwe College of Health Sciences (UZ-CHS) were vacant. To address the ongoing need to train highly skilled HIV clinicians with only a limited number of faculty, we developed and implemented a course for final-year medical students focused on HIV care using team-based learning (TBL) methods.MethodsA competency-based HIV curriculum was developed and delivered to final-year medical students in 10 TBL sessions as part of a 12 week clinical medicine attachment. A questionnaire was administered to the students after completion of the course to assess their perception of TBL and self-perceived knowledge gained in HIV care. Two cohorts of students completed the survey in separate academic years, 2011 and 2012. Descriptive analysis of survey results was performed.ResultsNinety-six of 120 students (80%) completed surveys. One hundred percent of respondents agreed that TBL was an effective way to learn about HIV and 66% strongly agreed. The majority of respondents agreed that TBL was more stimulating than a lecture course (94%), fostered enthusiasm for the course material (91%), and improved teamwork (96%). Students perceived improvements in knowledge gained across all of the HIV subjects covered, especially in challenging applied clinical topics, such as management of HIV antiretroviral failure (88% with at least a “large improvement”) and HIV-tuberculosis co-infection (80% with at least a “large improvement”).ConclusionsTBL is feasible as part of medical education in an African setting. TBL is a promising way to teach challenging clinical topics in a stimulating and interactive learning environment in a low-income country setting with a high ratio of students to teachers.

Presence of Betapapillomavirus in Kaposi sarcoma lesions

Human herpes virus 8 (HHV 8) is recognized as the necessary cause of Kaposi sarcoma (KS) and in the recent past the human papillomavirus (HPV) has been linked to the development of cutaneous basal cell and squamous cell carcinomas. In a cross sectional study investigating Beta‐HPV infections in skin lesions, an unexpected occurrence of HPV DNA was found in KS lesions of HIV infected individuals. Of the 18 KS cases included in the study 16 (89%) had HPV DNA detected. The most common Betapapillomavirus types were HPV14 [15 cases (83.3%)], HPV12 [8 cases (44.4%)], and HPV24 [7 cases (39%)]. Multiple Beta‐HPV types were detected in 10 (62.5%) of the participants with HPV DNA positive lesions; of these 7 had a CD4+ count below 350 cells/µl and 3 had CD4+ counts above 350 cells/µl. The presence of Beta‐HPV DNA in KS lesions is a newly described phenomenon. Further studies to elucidate the role of Beta‐HPV in KS need to be conducted as it is possible that HHV 8 may not be the solitary viral carcinogen in KS tumorigenesis. J. Med. Virol. 86:1556–1559, 2014.

AIDS-associated Kaposi sarcoma: outcomes after initiation of antiretroviral therapy at a university-affiliated hospital in urban Zimbabwe

OBJECTIVE To retrospectively investigate the outcomes of patients with AIDS-associated Kaposi sarcoma (AIDS-KS) after initiation of antiretroviral therapy (ART), under routine practice conditions, at a university-affiliated hospital in urban Zimbabwe. BACKGROUND While studies from developed nations have demonstrated excellent outcomes for AIDS-KS patients treated with ART, few studies have examined the outcomes of African AIDS-KS patients after starting therapy. METHODS A retrospective cohort of 124 AIDS patients initiating ART under routine practice conditions was studied. Thirty-one patients with AIDS-KS were matched 1:3 to 93 AIDS patients without KS (non-KS). The primary outcome was loss-to-care after initiation of therapy. Multivariate analysis was performed to identify significant predictors of loss-to-care. The percent change in weight at 6 months after starting ART was a secondary outcome. A sub-group analysis evaluated differences in pre-treatment variables between AIDS-KS patients retained-in-care compared to those lost-to-care. RESULTS AIDS-KS patients had significantly greater 2-year proportional loss-to-care than matched non-KS AIDS patients (26.4% vs. 9.5%; p = 0.01) after initiation of ART. In multivariate analysis, the presence of KS (p = 0.02) was the only significant predictor of loss-to-care. AIDS-KS patients had significantly less weight gain after starting ART than non-KS AIDS patients (+3.4% vs. +6.4%; p = 0.03). AIDS-KS patients retained-in-care had significantly higher pre-treatment CD4+ lymphocyte counts than AIDS-KS patients lost-to-care (223 vs. 110 cells/mm(3); p = 0.04). CONCLUSIONS In this retrospective study, AIDS-KS patients experienced significantly worse outcomes than matched non-KS AIDS patients after initiation of ART. AIDS-KS patients with higher pre-treatment CD4+ lymphocyte counts were more likely to be retained in care.

Innovations to Enhance the Quality of Health Professions Education at the University of Zimbabwe College of Health Sciences -NECTAR Program

The University of Zimbabwe College of Health Sciences (UZCHS) is Zimbabwe’s premier health professions training institution. However, several concerns were raised during the past decade over the quality of health education at UZCHS. The number of faculty and students declined markedly until 2010, when there was a medical student intake of 147 while the faculty comprised only 122 (39%) of a possible 314 positions. The economic and political crises that the country experienced from 1999 to 2009 compounded the difficulties faced by the institution by limiting the availability of resources. The Medical Education Partnership Initiative funding opportunity has given UZCHS the stimulus to embark on reforms to improve the quality of health education it offers. UZCHS, in partnership with the University of Colorado School of Medicine, the University of Colorado Denver Evaluation Center, and Stanford University, designed the Novel Education Clinical Trainees and Researchers (NECTAR) program to implement a series of health education innovations to meet this challenge. Between 2010 and 2013, innovations that have positively affected the quality of health professions education at UZCHS include the launch of comprehensive faculty development programs and mentored clinical and research programs for postgraduate students. A competency-based curriculum reform process has been initiated, a health professions department has been established, and the Research Support Center has been strengthened, providing critical resources to institutionalize health education and research implementation at the college. A core group of faculty trained in medical education has been assembled, helping to ensure the sustainability of these NECTAR activities.

Setting the research agenda in a resource-limited setting--viewpoint.

Abstract:The phenomenon of disproportionately large allocations of global health research resources to relatively limited components of the global health burden is widely acknowledged. Factors contributing to this are explored. The development of a national or regional research agenda is a critical step toward attempting to redress this imbalance. Key areas to be considered are a broad vision, dialogue, and commitment from those stakeholders comprising the “health research triangle”: national policy makers and decision makers, key personnel in both health research and health care, and community representatives. The interdependent roles of human, material, and community resources are further examined.

Relationship of vitamin D insufficiency to AIDS-associated Kaposi's sarcoma outcomes: retrospective analysis of a prospective clinical trial in Zimbabwe

OBJECTIVES The prevalence of vitamin D insufficiency in Africans with AIDS-associated Kaposi sarcoma (AIDS-KS) and the role of vitamin D in AIDS-KS progression are unknown. We hypothesized that a high prevalence of vitamin D deficiency would be found in Zimbabweans with AIDS-KS and that low baseline vitamin D would correlate with progression of AIDS-KS. METHODS Ninety subjects were enrolled in a prospective pilot study investigation of the effect of antiretroviral therapy in the treatment of AIDS-KS in Harare, Zimbabwe. Co-formulated abacavir, lamivudine, and zidovudine was initiated; chemotherapy was provided at the discretion of the provider. Participants were followed for 96 weeks. 25-Hydroxyvitamin D was measured in stored specimens collected at study entry. The relationship between vitamin D and clinical response was described by odds ratio and 95% confidence interval. RESULTS Samples were available for 85 participants; 45 (53%) subjects had inadequate (<75 nmol/l) 25-hydroxyvitamin D. HIV-1 RNA was significantly higher among those with insufficient vitamin D (4.7 vs. 4.5 log, p = 0.04). Tumor response, survival, and KS-IRIS were not associated with vitamin D (p ≥ 0.3). CONCLUSIONS Vitamin D insufficiency was common among Zimbabweans with AIDS-KS but not associated with outcomes after initiation of antiretroviral therapy.