Annular subvalvular left ventricular aneurysm: a case report

A clinical report on a rare form of disease (Annular sub-valvular left ventricular aneurysm) afflicting mostly black people as observed in Zimbabwe.Annular sub-valvular left ventricular aneurysm is a rare condition that has been described predominantly in southern and western African Black patients. Sporadic cases have, however, been reported among Blacks in several parts of Africa and indeed among a few Caucasians worldwide. A report in 1979 described the case of a Zimbabwean living in South Africa who died of complications related to this condition. Although the features of annular sub-valvular left ventricular aneurysm were recognized as early as 1813, it was Abrahams working in Nigeria in 1962 who described a series of 12 patients identifying this condition as a distinct clinico-pathological entity. In this article we report of a patient with annular sub-valvular aneurysm which perforated initially into the left atrium and later along the free wall causing sudden death of the patient

Acute myocardial infarction in Zimbabwe: the changing scene of coronary artery disease

From 1988 to 1993 (six years), 127 suspected cases of acute myocardial infarction (AMI) were admitted to the Parirenyatwa Hospital coronary care unit. AMI was confirmed in 76 cases, 37 were Black, 27 White, six Indian and six Coloured. For Blacks the male to female ratio was 5:1. The clinical and laboratory features and complications of AMI were similar in all ethnic groups. Compared to other groups, Blacks presented to hospital late, an observation which has important implications for thrombolytic therapy. With the increasing number of cases of AMI now being seen among Black Zimbabweans, the time has come for the evaluation of the changing risk factor profile and the initiation of education and intervention programmes which could contain this rise before it spirals into a major health problem

Metabolic Syndrome Disorders In Urban Black Zimbabweans With Type 2 Diabetes Mellitus

A CAJM field study.Objective: The main aim of the study was to determine the prevalence of metabolic syndrome disorders and their interrelations in black Zimbabwean type 2 diabetic patients. Study Design: Prospective cross sectional study. Setting: Outpatient diabetic clinics at Harare and Parirenyatwa tertiary hospitals. Main Outcome Measures: We recruited 109 adult diabetic subjects attending a tertiary hospital Diabetic Clinic. Anthropometric and metabolic parameters were measured by standard methods. Eighty percent of the patients were hypertensive, 32% dyslipidaemic, 32% obese, 50% hyperinsulinaemic, 61% had poor • glycaemic control and 43% of the participants had the metabolic syndrome. The means of BMI and triglycerides were significantly different in hyperinsulinaemic versus non-hyperinsulinaemic patients (p<0.001 and 0.041 respectively), and diastolic blood pressure was significantly raised in the obese group (p=0.043). The following significant associations were observed, hyperinsulinaemia with the metabolic syndrome (odds ratio=3.9, p<0.001) as well with obesity (odds ratio=4.8, p<0.001), however, only a weak association was observed between hypertension and hyperinsulinaemia (odds ratio=2.5, p=0.064). Patients exhibiting three metabolic disorders (dyslipidaemia, hypertension and obesity) were five times more likely to be hyperinsulinaemic (p=0.025) and hypertensive patients were almost three times more likely to, be hyperinsulinaemic. Conclusion: In comparison to their counterparts from certain ethnic groups, this urban diabetic population is also burdened with a variety of metabolic disorders which are risk factors for coronary artery disease. In this population, hyperinsulinaemia has a relatively weak association with hypertension and the relationship between obesity versus diastolic blood pressure as well as hypertriglyceridaemia versus serum insulin levels requires further investigation

Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052

Background: Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Methods: Complete next-generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). Results: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. Conclusions: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data

Virologic outcomes in early antiretroviral treatment: HPTN 052

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. Methods: 1566 participants who had a viral load (VL) &gt; 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 &lt; 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs &gt; 1000 copies/mL &gt; 24 weeks after ART initiation. Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention

Can Directionality of HIV Transmission be Predicted by Next-Generation Sequencing Data?

Background: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. Methods: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees. Results: DoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. Conclusions: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT

HIV Drug Resistance in Adults Receiving Early vs. Delayed Antiretroviral Therapy: HPTN 052

Introduction: We evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm 3 (early ART arm) or 1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure. Results: HIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure. Conclusions: In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136