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: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]

Diagnosis of KSHV-infected individuals remains a challenge. KSHV prevalence is high in several populations with high prevalence of HIV, leading to increased risk of development of Kaposi's sarcoma (KS). While current assays are reliable for detecting antibodies to KSHV, none are routinely utilized to identify individuals with KSHV infection and thus at increased risk for KS due to assay complexity, lack of access to testing, and cost, particularly in resource-limited settings. Here we describe the addition of KSHV proteins LANA and K8.1 to a previously evaluated HIV/co-infection multiplexed fluorescence immunoassay system. This study demonstrates assay performance by measuring antibody reactivity for KSHV and HIV-1 in a collection of clinical specimens from patients with biopsy-proven KS and sourced negative controls. The KSHV assay correctly identified 155 of 164 plasma samples from patients with biopsy-proven KS and 85 of 93 KSHV antibody (Ab)-negative samples for a sensitivity of 95.1% and specificity of 91.4%. Assay performance for HIV-1 detection was also assessed with 100% agreement with independently verified HIV-1 Ab-positive and Ab-negative samples. These results demonstrate good sensitivity and specificity for detection of antibody to KSHV antigens, and demonstrate the potential for multiplexed co-infection testing in resource-limited settings to identify those at increased risk for HIV-1-related complications., Competing Interests: This manuscript is a result of the collaboration between authors from the University of California, San Diego, the University of Colorado, and the commercial organization MBio Diagnostics, Inc. Funding was provided by the NIH directly to MBio Diagnostics under a Small Business Innovative Research grant for development of diagnostic technologies. Two authors of the manuscript are current employees of MBio Diagnostics, Inc. The authors’ affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

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., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

Background: Kaposi's sarcoma-associated herpesvirus (KSHV) encodes genetically diverse K1 alleles which have unique geographic distributions. Little is known about K1 genetic diversity in Zimbabwe where acquired immunodeficiency syndrome-associated KS (AIDS-KS) is epidemic., Objective: Evaluate K1 diversity in Zimbabwe and compare Zimbabwean K1 diversity to other areas in Africa., Study Design: K1 nucleotide sequence was determined for AIDS-KS cases in Zimbabwe. K1 references sequences were obtained from Genbank., Results: Among 65 Zimbabwean AIDS-KS cases, 26 (40%) were K1 subtype A and 39 (60%) were subtype B. Zimbabwean subtype A sequences grouped only with African intratype A5 variants. Zimbabwean subtype B sequences grouped with multiple intratype African variants: 26 B1 (26%), four B3 (6%) and nine highly divergent B4 (14%). Zimbabwean subtype B had a lower synonymous to nonsynonymous mutation ratio (median 0.59 versus 0.66; P=0.008) and greater distance to the most recent common ancestor (median 0.03 versus 0.009; P<0.001) compared to subtype A. Within the B subgroup, the distribution of intratype B variants differed in Zimbabwe and Uganda (P=0.004)., Conclusions: Greater positive selection and genetic diversity in K1 subtype B compared to subtype A5 exist in Zimbabwe. However, there were no significant associations between K1 subtype and the clinical or demographic characteristics of AIDS-KS cases.

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.

The relationship between Kaposi sarcoma-associated herpesvirus (KSHV) viremia and KS disease was investigated in 500 subjects who received treatment in Harare, Zimbabwe. Subjects were grouped by results of human immunodeficiency virus (HIV) type 1 serological tests, KS diagnosis, and KS clinical stage. The plasma KSHV DNA concentration was associated with concomitant KS and HIV-1 infection (AIDS-KS; P<.001) and AIDS-KS clinical stage (P=.01). Plasma KSHV DNA levels were greater in AIDS-KS than in matched HIV-1-seronegative KS (P=.04). The plasma KSHV DNA level was not associated with age, sex, systemic symptoms, or CD4+ lymphocyte count. Plasma and peripheral blood mononuclear cell KSHV DNA concentrations were linearly related (r2=.44; P<.001), and the nucleotide sequence of the K1 gene highly variable region was identical in both compartments. These findings provide evidence that KSHV viremia is common in advanced AIDS-KS in Zimbabwe and suggest a relationship between KSHV lytic replication and untreated HIV-1 infection.

Objective: To determine the relationship between human herpesvirus 8 (HHV-8 or Kaposi's sarcoma-associated herpesvirus) peripheral blood virus load and Kaposi's sarcoma (KS) clinical stage., Design: Blinded, cross-sectional analysis of peripheral blood HHV-8 DNA levels in persons with AIDS-related KS in Harare, Zimbabwe., Methods: Subjects 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., Results: Thirty-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/microg) 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)., Conclusion: The 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.

Objectives: To establish the ranges of full blood count (FBC), vitamin B12 and folate levels and to determine the prevalence of occult haematological abnormalities in older Zimbabweans., Study Design: Community based cross sectional survey., Subjects: 278 randomly selected healthy Zimbabweans aged > 65 years. INTERVENTIONS/STUDY FACTORS: Haemoglobin level, MCV, folate, B12 alcohol consumption., Results: The median Hb was males 14.0 (range 8 to 18.3), females 13.1 g/dl (7.9 to 18.1). 23% were anaemic (Hb < 13 g/dl in males, < 12 g/dl in females), 3% with microcytic and 20% with macrocytic indices. Overall 13% had low vitamin B12 and 30% had low folate levels. Folate levels were significantly lower in urban subjects and B12 levels were significantly lower in rural subjects. Fifty four subjects (21%) had an MCV > 100 fl. In this group, low folate levels were found in 22, low B12 levels in nine, excessive alcohol in eight and two subjects had elevated TSH. The MCV was higher in urban subjects., Conclusions: This study has revealed a large amount of occult haematological abnormality and interesting differences between rural and urban subjects. It focuses attention on low levels of folate, which should be preventable by simple nutritional education, as an extensive problem in the community.

Fifty consecutive patients presenting with upper gastrointestinal haemorrhage caused by oesophageal varices were subjected to endoscopic sclerotherapy during the period April 1989 to December 1991. Portal hypertension was caused by alcoholic liver cirrhosis in 22 (44pc), Hepatitis B induced liver cirrhosis in seven (14pc), cryptogenic liver cirrhosis in three (six pc), bilharzial portal fibrosis in 17 (34pc) and extrahepatic portal obstruction in one (two pc). Acute bleeding was controlled in 12 out of 13 patients, five of whom with a fresh bleed and eight who rebled while on the endoscopic sclerotherapy regimen. All patients were treated on a weekly sclerotherapy regimen. Reduction in variceal size of two or more grades was achieved in all 30 patients who had completed at least four or more endoscopic sclerotherapy courses with total eradication of varices in 27 (90pc). Three patients died. All deaths were caused by progressive hepatic encephalopathy. Complications usually seen were retrosternal pain, fever, dysphagia and oesophageal ulceration. There were no fatal complications. The study shows that endoscopic sclerotherapy is effective not only in controlling acute bleeding but also in preventing rebleeding. We recommend a weekly schedule for the early eradication of varices.