Renal and metabolic toxicities following initiation of HIV-1 treatment regimen in a diverse, multinational setting: a focused safety analysis of ACTG PEARLS (A5175).

BACKGROUND: Convenient dosing, potency, and low toxicity support use of tenofovir disoproxil fumarate (TDF) as preferred nucleotide reverse transcriptase inhibitor (NRTI) for HIV-1 treatment. However, renal and metabolic safety of TDF compared to other NRTIs has not been well described in resource-limited settings. METHODS: This was a secondary analysis examining the occurrence of renal abnormalities (RAs) and renal and metabolic serious non-AIDS-defining events (SNADEs) through study follow-up between participants randomized to zidovudine (ZDV)/lamivudine/ efavirenz and TDF/emtricitabine/efavirenz treatment arms within A5175/PEARLS trial. Exact logistic regression explored associations between baseline covariates and RAs. Response profile longitudinal analysis compared creatinine clearance (CrCl) over time between NRTI groups. RESULTS: Twenty-one of 1,045 participants developed RAs through 192 weeks follow-up; there were 15 out of 21 in the TDF arm (P = .08). Age 41 years or older (odds ratio [OR], 3.35; 95% CI, 1.1-13.1), his- tory of diabetes (OR, 10.7; 95% CI, 2.1-55), and lower baseline CrCl (OR, 3.1 per 25 mL/min decline; 95% CI, 1.7-5.8) were associated with development of RAs. Renal SNADEs occurred in 42 participants; 33 were urinary tract infections and 4 were renal failure/insufficiency; one event was attributed to TDF. Significantly lower CrCl values were maintained among patients receiving TDF compared to ZDV (repeated measures analysis, P = .05), however worsening CrCl from baseline was not observed with TDF exposure over time. Metabolic SNADEs were rare, but were higher in the ZDV arm (20 vs 3; P < .001). CONCLUSIONS: TDF is associated with lower serious metabolic toxicities but not higher risk of RAs, serious renal events, or worsening CrCl over time compared to ZDV in this randomized multinational study.

Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients.

OBJECTIVE: To determine the causative organisms and characteristics of patients presenting with features of meningitis. DESIGN: A prospective cross-sectional study. SETTING: Two tertiary university-affiliated hospitals in Harare, Zimbabwe. PATIENTS: Four-hundred and six patients clinically suspected to have meningitis. MAIN OUTCOME MEASURES: Causative organisms of meningitis; clinical and cerebrospinal fluid characteristics. RESULTS: Four-hundred and six predominantly adult (95% were aged > or = 18 years) patients were suspected to have meningitis. Of the 200 patients confirmed to have meningitis, 89 (45%) had cryptococcal meningitis (CM), 54 (27%) had mononuclear meningitis (MM), 31 (16%) had pyogenic meningitis (PM), 24 (12%) had tuberculous meningitis (TBM) and 2 (1%) had undefined meningitis. HIV seropositivity was 100% in CM, 83% in MM, 81% in PM and 88% in TBM patients. In-hospital mortality rate was 38.8% for CM, 34.9% for MM, 68% for PM and 66.7% for TBM. HIV seropositivity was 80% in the 206 patients not found to have meningitis. CONCLUSIONS: All patients suspected to have meningitis had a high HIV sero positivity irrespective of whether they were later confirmed to have meningitis or not. CM was the most common type of meningitis seen. In-hospital mortality was high irrespective of the cause of meningitis.

Myocardial dysfunction in human immunodeficiency virus infection: an echocardiographic study of 157 patients in hospital in Zimbabwe.

OBJECTIVE: To determine the prevalence and characteristics of myocardial dysfunction and other cardiac manifestations in acutely ill hospital patients infected with human immunodeficiency virus (HIV) in Zimbabwe. DESIGN: A prospective echocardiographic survey of acutely ill HIV seropositive patients. SETTING: General medical ward, Harare Central Hospital, Zimbabwe. PATIENTS: One hundred and fifty seven HIV seropositive patients admitted with various acute medical conditions over a 12 month period, January to December 1994. MAIN OUTCOME MEASURES: Detection of myocardial dysfunction and other cardiac abnormalities by cross sectional echocardiography. RESULTS: Eighty (51%) men and 77 women were studied (mean (SD) age 34.4 (8.5), range 15-60 years for males and 31.6 (9.0), range 16-65 years for females). They were all heterosexual. None was haemophiliac or an intravenous drug user. Echocardiographic abnormalities were found in 79 (50%) patients: 14/151 (9%) had dilated cardiomyopathy, 33/151 (22%) left ventricular dysfunction, 9/151 isolated right ventricular dilatation, and 30/157 (19%) pericardial disease (28 with effusions, three having tamponade). There were two cases of constrictive pericarditis and one of ascending aortic aneurysm. CONCLUSIONS: There is a high prevalence of echocardiographically detected myocardial and pericardial disease in this group of acutely ill HIV infected patients. Left ventricular dysfunction without dilatation was common, but its significance was not ascertained.

Hepatitis C virus and HIV antibodies in patients with hepatocellular carcinoma in Zimbabwe: a pilot study.

To determine the role of hepatitis C virus (HCV) infection in the aetiology of hepatocellular carcinoma (HCC) in Zimbabwe, HCV antibodies (anti-HCV) were determined in sera from 63 HCC patients using a second generation enzyme immunoassay. Anti-HCV was found in 15 patients (23.8%), 12 of whom (80%) were males. The mean ages of anti-HCV positive and anti-HCV negative patients were 62.1 (SD = 10.6) and 44.3 (SD = 15.2) years, respectively (P < 0.001). HIV antibodies were found in 17/59 patients (28.8%), 12 of whom (70.6%) were males. The mean ages of HIV positive and HIV negative patients were 39.4 (SD = 15.2) and 51.0 (SD = 15.2) years (P = 0.011). Hepatitis B surface antigen (HBsAg) was detected in 26/61 patients (42.6%) with mean ages of HBsAg positive vs negative patients of 41.5 (SD = 15.4) years for HIV positive and 53.1 (SD = 15.1) years for HIV negative subjects (P = 0.005). Younger HCC patients had high prevalences of HBsAg and anti-HIV and a low prevalence of anti-HCV; while older patients had a high prevalence of anti-HCV and low prevalences of HBsAg and anti-HIV. This study suggested that HCV infection is probably an important aetiological agent of HCC in Zimbabwe; however, the role of HIV infection as a cause of HCC either singly or as a co-factor with hepatitis B virus infection remains speculative and warrants further study.

PIP: Several studies have reported a high prevalence of hepatitis C virus (HCV) antibodies (anti-HCV) in patients with hepatocellular carcinoma (HCC). In addition, HIV infection may be a causative factor for HCC. To determine the role of HCV infection in the etiology of HCC in Zimbabwe, the presence of anti-HCV was assessed in sera from 63 HCC patients using a second-generation enzyme immunoassay. Anti-HCV was isolated in 15 patients (23.8%), of whom 12 were male. The mean ages of anti-HCV-positive and anti-HCV-negative patients were 62.1 and 44.3 years, respectively. HIV antibodies were found in 17 (28.8%) of 59 patients, of whom 12 were male. The mean ages of HIV-positive and HIV-negative patients were 39.4 and 51.0 years, respectively. Hepatitis B surface antigen (HBsAg) was detected in 26 of 61 patients (42.6%), with the mean ages of HBsAg-positive versus HBsAg-negative patients of 41.5 years for HIV-positive and 53.1 years for HIV-negative subjects. Younger HCC patients had high prevalences of HBsAg and anti-HIV, and a low prevalence of anti-HCV, while older patients had a high prevalence of anti-HCV and low prevalences of HBsAg and anti-HIV. These findings suggest that HCV infection is probably an important etiological agent of HCC in Zimbabwe.

Opsoclonus-myoclonus associated with traditional medicine ingestion: case report.

A case of Opsoclonus-Myoclonus occurring in a young man, in association with traditional herbal medicine consumption is presented. Clinical and laboratory investigations did not reveal any of the known aetiological associations of the Opsoclonus-Myoclonus syndrome, raising the possibility that the traditional herbal medicine may be aetiologically implicated. This report highlights the need for proper identification and documentation of the contents of common herbal remedies and their possible side effects amongst Africans.

Echocardiographic assessment of left ventricular hypertrophy diastolic dysfunction and pericardial disease in patients on maintenance haemodialysis.

Echocardiographic study of sixty patients on maintenance haemodialysis (MHD) was undertaken to determine the prevalence and factors associated with left ventricular (LV) hypertrophy (LVH), LV diastolic dysfunction and pericardial disease. The mean age was 34.4 (standard deviation 13.0), range 14-66 years with 31 (51.7%) men. LVH was found in 41 (68%) patients. Of the factors analysed, serum calcium and calcium-phosphate product were significantly associated with LVH (t = 2.01, df = 58, p = 0.046; t = 2.18, df = 58, p = 0.032 respectively). Hypertension in this study was not significantly associated with LVH (p = 0.169). LV diastolic dysfunction was found in 23/41 (56%) patients with LVH, and in 9/19 (47%) patients without LVH (difference is not statistically significant, X2 = 0.12, df = 1, p = 0.725). Small pericardial effusions were detected in 4/60 (7%) patients and two patients had pericardial thickening. We conclude that in our MHD patients LVH, is very common and that diastolic dysfunction is observed equally in patients with and without LVH. However, haemodynamically significant pericardial effusions are rare in patients who have been on dialysis for at least six months.

Differential human immunodeficiency virus risk factors among female general nurses, nurse midwives and office workers/teachers in Zambia.

OBJECTIVES: To determine whether the factors associated with human immunodeficiency virus (HIV) infection are the same among the general nurses, nurse midwives and office workers/teachers. DESIGN: Cross sectional. SETTING: Schools, offices and hospitals. SUBJECTS: A total of 370 consenting females from each of the study groups. MAIN OUTCOME MEASURES: HIV seropositivity, medical and behavioural risk factors for HIV infection. RESULTS: HIV seropositive general nurses were more likely to report a history of sexually transmitted disease since 1980 (OR 5.17; 95pc CI 1.60 to 15.05), particularly genital ulcer (OR 3.59; 95pc CI 1.30 to 10.85), and they were also more likely to have more sexual partners (OR 4.08; 95pc CI 1.54 to 13.11). HIV seropositive nurse midwives were more likely to have had a blood transfusion (OR 2.17; 95pc CI 1.13 to 4.14), and HIV seropositive office workers/teachers were more likely to have scarification (OR 1.66; 95pc CI 1.07 to 2.57). CONCLUSIONS: Our findings support the importance of genital ulcers, blood transfusion and scarification as risk factors for HIV intervention studies should be specifically targeted to the sector of the population under study.

Cardiac disease distribution among patients referred for echocardiography in Harare, Zimbabwe.

OBJECTIVE: To determine the distribution of cardiac diseases seen in a tertiary referral hospital. DESIGN: Cross sectional survey. SETTING: Harare Central Hospital, Harare, Zimbabwe. SUBJECTS: 1,507 patients referred for echocardiographic evaluation. MAIN OUTCOME MEASURE: Cardiac diagnosis. RESULTS: 1,153 (76.5%) echocardiographic studies were abnormal, while 354 were normal. Rheumatic heart disease was the predominant diagnosis (25.1%) with 208 (74.3%) of cases being females. The main valvular lesion in females was mitral stenosis (48.1%), while in males it was mitral regurgitation (61.1%). Other diagnoses were: pericardial disease 250 (22.4%), dilated cardiomyopathy 245 (22.0%), hypertensive heart disease 148 (13.3%) and others (17.4%). There were 65 cases of peripartum cardiomyopathy among the cases of dilated cardiomyopathy and 34 cases of acute myocarditis among "others". CONCLUSION: A detailed clinical, radiological and echocardiographic assessment at the time of echocardiography enabled a credible diagnosis to be assigned to the majority of patients. Echocardiography is appropriate technology in this setting given the range of "echo-friendly" cardiac lesions found.

Why beta blockers should be used in heart failure.

Beta blockade may be beneficial for most patients with congestive cardiac failure (CCF) whether due to ischaemic or idiopathic dilated cardiomyopathy (DCM), although they are more effective if the CCF is idiopathic. Beta blockers are additive to angiotensin converting enzyme (ACE) inhibitors in their effects on CCF. Beta blockers have been shown in most studies to increase ejection fraction, cardiac output, and exercise capacity and are sometimes capable of resolving almost all the symptoms of heart failure. Treatment should begin with the smallest possible dose and this should be gradually increased to the maximum tolerated level.

Endomyocardial fibrosis in Zimbabwe--how rare is it? A report of two cases.

In Africa endomyocardial fibrosis (EMF) is rare outside countries where it is endemic, such as Uganda, Mozambique and Ivory Coast. The only published case in Zimbabwe was in 1957. We describe two female patients aged 22 and 19 years who presented within seven months of each other with typical clinical, electrocardiographic and echocardiogaphic features of right ventricular EMF. We would like to suggest that EMF exists in Zimbabwe and needs to be considered in the differential diagnosis of patients presenting with suggestive clinical features.

Metabolic syndrome disorders in urban black Zimbabweans with type 2 Diabetes mellitus.

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.

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.

Non-condom use among female nurses in Zambia.

OBJECTIVES: To estimate non-condom user rate and to characterize non-condom users among female nurses. DESIGN: Cross sectional. SETTING: Health institutions. SUBJECTS: Data from 640 (86.5pc) out of 740 consenting female nurses were available for analyses. MAIN OUTCOME MEASURE: Non-condom user rate. RESULTS: Non-condom user rate (per 100) among the female nurses was 73.1pc (95pc CI69.7 to 76.5). Non-condom users tended to be aged above 30 years (OR 1.57; 95pc CI 1.02 to 2.40), midwives (OR 1.56; 95pc CI 1.03 to 2.37), married (OR 2.70; 95pc CI 1.73 to 4.21), not to think that spouse/partner has had sex with other partners (OR 1.72; 95pc CI 1.11 to 2.68) and to have had a sexually transmitted disease (OR 2.61; 95pc CI 1.25 to 5.43). CONCLUSION: There was a surprising high level of non-condom users among female nurses, probably due to the inability for females to initiate or negotiate condom use.

PIP: A cross sectional study covering 30 main health institutions in all the 9 provinces of Zambia was carried out using data collected in 1992 from nurses who filled in a self-administered questionnaire. The data from 640 nurses were analyzed: 316 were midwives. 30.9% of this sample was in the 30-34 year old age group and 71.7% were married. The non-condom use rate among them was 73.1%. The results of the bivariate analyses of various factors indicated significant findings: nurses 30 years and older were associated with non-condom use (odds ratio [OR] 1.97); and nurse midwives were 1.78 times more likely not to use condoms. Married nurses were 2.37 times more likely not to use condoms. Nurses who lived in consensual union with their sexual partners were 2.5 times more likely not to use condoms, while nurses who had one sexual partner were 2.65 times more likely not to use condoms. Nurses who did not think that their spouses or partners had sex with other partners were 2.05 times more likely not to use condoms. Nurses who had sexually transmitted diseases were 2.17 times more likely not to use condoms. Logistic regression analysis included age (30 and older), occupation for midwives, marital status, no sex life of spouse-partner with other partners, and ever having STDs. It demonstrated that the ORs and their 95% confidence intervals obtained using forward stepwise logistic regions were exactly the same as for those obtained using the backward stepwise logistic regression. Only the factors relating to the frequency of living together with sexual partners and the number of sexual partners were dropped from the model. The adjusted ORs did not differ statistically from the unadjusted one at the 5% significance level. Further studies to enhance condom use should examine the empowering of both women and men to negotiate for safer sex.

Fine needle aspiration cytology in the diagnosis of hepatocellular carcinoma.

Fine needle aspiration (FNA) of the liver without ultrasound guidance was performed on 110 patients with hepatocellular carcinoma (HCC). The median age was 52 years, with a range of 16 to 86 years. There were 90 males and 20 females (a male: female ratio of 4.5:1), with a median age of 51.5 years (range 16 to 86 years) and 55.5 years (range 17 to 72 years) respectively. FNA was reported as showing malignancy in 92 (84 pc, 95 pc CI 77 to 91 pc) patients; 80 (73 pc) were definite HCC, 12 (11 pc) were malignant unspecified, seven (6 pc) were suspicious of malignancy, seven (6 pc) had no malignant cells and four (4 pc) were non-diagnostic. The only complication observed was dizziness in one patient. We conclude that FNA of the liver for the diagnosis of HCC is a safe, simple and accurate procedure which can be undertaken in settings that would otherwise not be suitable for formal liver biopsy.

Double blind randomised placebo controlled trial of adjunctive prednisolone in the treatment of effusive tuberculous pericarditis in HIV seropositive patients.

OBJECTIVE: To determine the effect of adjunctive prednisolone on morbidity, pericardial fluid resolution, and mortality in HIV seropositive patients with effusive tuberculous pericarditis. DESIGN: Double blind randomised placebo controlled trial. SETTING: Two medical school affiliated referral hospitals in Harare, Zimbabwe. PATIENTS: 58 HIV seropositive patients aged 18-55 years with tuberculous pericarditis. INTERVENTIONS: All patients received standard short course antituberculous chemotherapy and were randomly assigned to receive prednisolone or placebo for six weeks. MAIN OUTCOME MEASURES: Clinical improvement, echocardiographic and radiologic pericardial fluid resolution, and death. RESULTS: 29 patients were assigned to prednisolone and 29 to placebo. After 18 months of follow up there were five deaths in the prednisolone treated group and 10 deaths in the placebo group. Mortality was significantly lower in the prednisolone group (log rank chi(2) = 8. 19, df = 1, p = 0.004). Resolution of raised jugular venous pressure (p = 0.017), hepatomegaly (p = 0.007), and ascites (p = 0.015), and improvement in physical activity (p = 0.02), were significantly more rapid in the prednisolone treated patients. However, there was no difference in the rate of radiologic and echocardiographic resolution of pericardial effusion. CONCLUSIONS: Adjunctive prednisolone for effusive tuberculous pericarditis produced a pronounced reduction in mortality. It is suggested prednisolone should be added to standard short course chemotherapy to treat HIV related effusive tuberculous pericarditis.

Cryptococcus myelitis: atypical presentation of a common infection.

Cryptococcus neoformans is associated with as much as 45% of meningitis in patients admitted for hospital care in Zimbabwe, and it is an important opportunistic infection in patients infected with the human immunodeficiency virus. Cases of cryptococcosis presenting as a spinal cord syndrome have been reported from Zimbabwe and South Africa, but these were all cases of Cryptococcus vertebral osteomyelitis. We describe 3 unusual patients who presented with a myelitis-like syndrome without vertebral osteomyelitis.

Cryptococcal meningitis in human immunodeficiency virus-infected patients in Harare, Zimbabwe.

A prospective observational study was conducted over a 10-month period to determine the clinical and laboratory manifestations of cryptococcal meningitis in Zimbabwe, a country where antifungal agents are not widely available. Eighty-nine patients with cryptococcal meningitis (median age, 34 years; range, 11-63 years; 56 males) were identified from 406 patients for whom a clinical diagnosis of meningitis had been made. All patients tested were positive for antibody to human immunodeficiency virus. Cryptococcal meningitis was the first AIDS-defining illness in 88% of patients. Typical presentations were headache, mental impairment, and meningism (median duration, 14 days; range, 1-180 days). The median CD4+ cell count was 70/microL (range, 0-651/microL). The cumulative median survival from the time of diagnosis was 14 days (range, 0-233 days); 22% of patients survived for >30 days. Independent indicators of a good prognosis were not identified. This study provides a unique basis for the development of novel management strategies for patients with cryptococcal meningitis who reside in resource-poor countries.

Comparative skin testing with PPD tuberculin, Mycobacterium avium and M. scrofulaceum sensitin in schoolchildren in Saudi Arabia.

SETTING: Jizan region, Saudi Arabia. OBJECTIVE: To test methodology for studies of tuberculin sensitivity and effectiveness of BCG vaccination programme. DESIGN: School children (n = 315) aged 6-12 years simultaneously tested intradermally with PPD tuberculin RT23, 2TU and 0.1 microgram Mycobacterium avium or M. scrofulaceum sensitin. Presence of BCG scar as evidence of previous BCG vaccination. Cervical lymph nodes palpated. RESULTS: BCG coverage was 75%. The prevalences of positive reactions (induration > or = 6 mm) were higher among children with than without scar. Prevalences of positive reactions to PPD and M. scrofulaceum sensitin were higher among girls than boys. In children with scar, the mean size of positive reactions to PPD was larger among girls than boys, and the prevalence of positive reactions was smaller in this group among children with than without palpable cervical lymph nodes. The sizes of reactions both to M. avium and to M. scrofulaceum sensitin were correlated to the size of the tuberculin reactions. Previous admission to hospital was reported less often by children with than without scar. CONCLUSIONS: The technique applied and training of staff was satisfactory. In further studies, however, we will apply three simultaneous tests to each person.