A viral genome wide association study and genotypic resistance testing in patients failing first line antiretroviral therapy in the first large countrywide Ethiopian HIV cohort.

BACKGROUND: Antiretroviral therapy (ART) was rolled-out in Ethiopia in 2005, but there are no reports on outcome of ART and human immunodeficiency virus drug resistance (HIVDR) at national level. We described acquired drug resistance mutations in pol gene and performed a viral genome wide association study in virologic treatment failure patients who started first line ART during 2009-2011 in the first large countrywide HIV cohort in Ethiopia. METHODS: The outcome of tenofovir (TDF)- and zidovudine (ZDV)-based ART was defined in 874 ART naïve patients using the on-treatment (OT) and intention-to-treat (ITT) analyses. Genotypic resistance testing was done in patients failing ART (> 1000 copies/ml) at month 6 and 12. Near full-length genome sequencing (NFLG) was used to assess amino acid changes in HIV-1 gag, pol, vif, vpr, tat, vpu, and nef genes between paired baseline and month 6 samples. RESULTS: High failure rates were found in ITT analysis at month 6 and 12 (23.3%; 33.9% respectively). Major nucleoside and non-nucleoside reverse transcriptase (NRTI/NNRTI) drug resistance mutations were detected in most failure patients at month 6 (36/47; 77%) and month 12 (20/30; 67%). A high rate of K65R was identified only in TDF treated patients (35.7%; 50.0%, respectively). No significant difference was found in failure rate or extent of HIVDR between TDF- and ZDV- treated patients. All target regions of interest for HIVDR were described by NFLG in 16 patients tested before initiation of ART and at month 6. CONCLUSION: In this first Ethiopian national cohort, a high degree of HIVDR was seen among ART failure patients, independent on whether TDF- or ZDV was given. However, the major reason to ART failure was lost-to-follow-up rather than virologic failure. Our NFLG assay covered all relevant target genes for antiretrovirals and is an attractive alternative for HIVDR surveillance.

Baseline predictors of antiretroviral treatment failure and lost to follow up in a multicenter countrywide HIV-1 cohort study in Ethiopia.

BACKGROUND: Antiretroviral therapy (ART) has been rapidly scaled up in Ethiopia since 2005, but factors influencing the outcome are poorly studied. We therefore analysed baseline predictors of first-line ART outcome after 6 and 12 months. MATERIAL AND METHODS: 874 HIV-infected patients, who started first-line ART, were enrolled in a countrywide prospective cohort. Two outcomes were defined: i) treatment failure: detectable viremia or lost-to-follow-up (LTFU) (confirmed death, moved from study sites or similar reasons); ii) LTFU only. Using stepwise logistic regression, four multivariable models identified baseline predictors for odds of treatment failure and LTFU. RESULTS: The treatment failure rates were 23.3% and 33.9% at 6 and 12 months, respectively. Opportunistic infections (OI), tuberculosis (TB), CD4 cells <50/µl, and viral load >5 log10 copies/ml increased the odds of treatment failure both at 6 and 12 months. The odds of LTFU at month 6 increased with baseline functional disabilities, WHO stage III/IV, and CD4 cells <50/µl. TB also increased the odds at month 12. Importantly, ART outcome differed across hospitals. Compared to the national hospital in Addis Ababa, patients from most regional sites had higher odds of treatment failure and/or LTFU at month 6 and/or 12, with the exception of one clinic (Jimma), which had lower odds of failure at month 6. CONCLUSIONS: In this first countrywide Ethiopian HIV cohort, a high ART failure rate was identified, to the largest extent due to LTFU, including death. The geographical region where the patients were treated was a strong baseline predictor of ART failure. The difference in ART outcome across hospitals calls the need for provision of more national support at regional level.

Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing.

Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also next generation sequencing (NGS) was used in a subset of 109 baseline samples of patients. Treatment outcome after 6- and 12-months was assessed by on-treatment (OT) and intention-to-treat (ITT) analyses. Transmitted drug resistance (TDR) was detected in 3.9% (18/461) of successfully sequenced samples by PBSS. However, NGS detected sDRM more often (24%; 26/109) than PBSS (6%; 7/109) (p = 0.0001) and major integrase strand transfer inhibitors (INSTI) DRMs were also found in minor viral variants from five patients. Patients with sDRM had more frequent treatment failure in both OT and ITT analyses. The high rate of TDR by NGS and the identification of preexisting INSTI DRMs in minor wild-type HIV-1 subtype C viral variants infected Ethiopian patients underscores the importance of TDR surveillance in low- and middle-income countries and shows added value of high-throughput NGS in such studies.

Coreceptor Tropism and Maraviroc Sensitivity of Clonally Derived Ethiopian HIV-1C Strains Using an in-house Phenotypic Assay and Commonly Used Genotypic Methods.

OBJECTIVES: Genotypic Tropism Testing (GTT) tools are generally developed based on HIV-1 subtype B (HIV-1B) and used for HIV-1C as well but with a large discordance of prediction between different methods. We used an established phenotypic assay for comparison with GTT methods and for the determination of in vitro maraviroc sensitivity of pure R5-tropic and dual-tropic HIV-1C. METHODS: Plasma was obtained from 58 HIV-1C infected Ethiopians. Envgp120 was cloned into a luciferase tagged NL4-3 plasmid. Phenotypic tropism was determined by in house method and the V3 sequences were analysed by five GTT methods. In vitro maraviroc sensitivity of R5-tropic and dual-tropic isolates were compared in the TZMbl cell-line. RESULTS: The phenotypes were classified as R5 in 92.4% and dual tropic (R5X4) in 7.6% of 79 clones. The concordance between phenotype and genotype ranged from 64.7% to 84.3% depending on the GTT method. Only 46.9% of the R5 phenotypes were predicted as R5 by all GTT tools while R5X4 phenotypes were predicted as X4 by four methods, but not by Raymond's method. All six tested phenotypic R5 clones, as well as five of six of dual tropic clones, showed a dose response to maraviroc. CONCLUSION: There is a high discordance between GTT methods, which underestimates the presence of R5 and overestimates X4 strains compared to a phenotypic assay. Currently available GTT algorithms should be further improved for tropism prediction in HIV-1C. Maraviroc has an in vitro activity against most HIV-1C viruses and could be considered as an alternative regimen in individuals infected with CCR5-tropic HIV-1C viruses.

Prediction of coreceptor usage by five bioinformatics tools in a large Ethiopian HIV-1 subtype C cohort.

BACKGROUND: Genotypic tropism testing (GTT) has been developed largely on HIV-1 subtype B. Although a few reports have analysed the utility of GTT in other subtypes, more studies using HIV-1 subtype C (HIV-1C) are needed, considering the huge contribution of HIV-1C to the global epidemic. METHODS: Plasma was obtained from 420 treatment-naïve HIV-1C infected Ethiopians recruited 2009-2011. The V3 region was sequenced and the coreceptor usage was predicted by five tools: Geno2Pheno clinical-and clonal-models, PhenoSeq-C, C-PSSM and Raymond's algorithm. The impact of baseline tropism on antiretroviral treatment (ART) outcome was evaluated. RESULTS: Of 352 patients with successful baseline V3 sequences, the proportion of predicted R5 virus varied between the methods by 12.5% (78.1%-90.6%). However, only 58.2% of the predictions were concordant and only 1.7% were predicted to be X4-tropic across the five methods. Compared pairwise, the highest concordance was between C-PSSM and Geno2Pheno clonal (86.4%). In bivariate intention to treat (ITT) analysis, R5 infected patients achieved treatment success more frequently than X4 infected at month six as predicted by Geno2Pheno clinical (77.8% vs 58.7%, P = 0.004) and at month 12 by C-PSSM (61.9% vs 46.6%, P = 0.038). However, in the multivariable analysis adjusted for age, gender, baseline CD4 and viral load, only tropism as predicted by C-PSSM showed an impact on month 12 (P = 0.04, OR 2.47, 95% CI 1.06-5.79). CONCLUSION: Each of the bioinformatics models predicted R5 tropism with comparable frequency but there was a large discordance between the methods. Baseline tropism had an impact on outcome of first line ART at month 12 in multivariable ITT analysis but only based on prediction by C-PSSM which thus possibly could be used for predicting outcome of ART in HIV-1C infected Ethiopians.

Establishing a Multicenter Longitudinal Clinical Cohort Study in Ethiopia: Advanced Clinical Monitoring of Antiretroviral Treatment Project.

BACKGROUND: The purpose of this paper is to describe the establishment of the Advanced Clinical Monitoring of ART Project in Ethiopia for monitoring and evaluation of the longitudinal effectiveness of the ART program and to show the opportunities it presents. This cohort was established in response to the 2005 call by WHO for establishing additional mechanisms for stronger monitoring of ART and the need for creating the platform to generate evidence to guide the care given for the ever increasing number of patients on ART in Ethiopia. METHOD: A participatory and multi-stage process which started from a consensus building workshop and steered by a mother protocol as well as guiding documents which dictated the degree of engagement and expectations was followed. The primary and secondary aims of the study were agreed upon. A multi-site longitudinal observational clinical cohort was established by a consortium of stakeholders including seven Ethiopian medical schools and their affiliated referral hospitals, John Hopkins University, Ethiopian Public Health Institute, Ministry of Science and Technology, US Centers for Disease Prevention and Control - CDC-Ethiopia, and the Federal Ministry of Health. Adult and adolescent cohorts covering the age range of 14+ years) and pediatric cohorts covering those below age 14 years were the two main cohorts. During the initial recruitment of these cohorts information was extracted from existing documents for a total of 2,100 adult participants. In parallel, a prospective cohort of 1,400 adult and adolescent patients were enrolled for ART initiation and follow-up. Using similar recruitment procedures, a total of 120 children were enrolled in each of retrospective and prospective cohorts. Replacement of participants were made in subsequent years based on lost follow up and death rates to maintain adequacy of the sample to be followed-up. ACHIEVEMENTS: Between January 2005 and August 2013 a total of 4,339 patients were followed for a median of 41.6 months and data on demographic characteristics, baseline and ongoing clinical features, hospitalization history, medication and laboratory information were collected. 39,762 aliquots and 25,515 specimens of plasma and dryblood-spots respectively were obtained and stored longitudinally from October 2009 to August 2013. The project created a research platform for researchers, policy and decision makers. Moreover, it encouraged local and international investigators to identify and answer clinically and programmatically relevant research questions using the available data and specimens. Calls for concept notes paired with multiple trainings to stimulate investigators to conduct analyses further boosted the potential for doing research. CONCLUSIONS: A comprehensive and resourceful mechanism for scientific inquiry was established to support the national HIV/ART program. With meaningful involvement and defined roles, establishment of a study, which involved multiple institutions and investigators, was possible. Since ACM is the largest multi-site clinical cohort of patients on antiretroviral treatment in Ethiopia-which can be used for research and for improving clinical management-considering options to sustain the project is crucial.

Predictors of Survival among Adult Ethiopian Patients in the National ART Program at Seven University Teaching Hospitals: A Prospective Cohort Study.

BACKGROUND: In Ethiopia, the publicly funded antiretroviral treatment (ART) program was started in 2005. Two hundred seventy-five thousand patients were enrolled in the national ART program by 2012. However, there is limited data on mortality and predictors of death among adult patients in the ART program. The study aimed to estimate mortality and risk factors for death among adult, ART-naïve patients, started in the national ART program from January 2009 to July 2013. METHODS: Multi-site, prospective, observational cohort study of adult, age > 18 years, ART-naïve patients, started in the national ART program at seven university-affiliated hospitals from January 2009 - July 2013. Kaplan-Meier and Cox regression analyses were used to estimate survival and determine risk factors for death. RESULTS: A total of 976 patients, 594 females (60.9 %), were enrolled into the study. Median age of the cohort was 33years. The median CD4 count at start of ART was 144 cells/µl (interquartile range (IQR) 78-205), and 34.2% (330/965) had CD4 < 100. Sixty-three percent (536/851) had viral load greater than 5 log copies/ml (IQR 4.7-5.7) at base line. One hundred and one deaths were recorded during follow-up period, all-cause mortality rate 10.3%; 5.4 deaths/100 person years of observation, 95% confidence interval 4.4-6.5. Seventy percent of the deaths occurred within six months of starting ART. Cox regression analyses showed that the following measures independently predicted mortality: age >51 years, (Adjusted Hazard Ratio (AHR) 4.01, P=0.003), WHO stages III&IV, (AHR 1.76, p = 0.025), CD4 count, <100, (AHR 2.36, p =0.006), and viral load >5 log copies /ml (CHR 1.71, p = 0.037). CONCLUSION: There is high early on- ART mortality in patients presenting with advanced immunodeficiency. Detecting cases and initiating ART before onset of advanced immunodeficiency might improve survival.

Monophylogenetic HIV-1C epidemic in Ethiopia is dominated by CCR5-tropic viruses-an analysis of a prospective country-wide cohort.

BACKGROUND: CCR5 coreceptor using HIV-1 subtype C (HIV-1C) has been reported to dominate the Ethiopian epidemic. However, almost all data have been obtained from two large cities in the central and north-west regions and recent data is lacking. METHODS: Plasma were obtained from 420 treatment-naïve patients recruited 2009-2011 to a large country-wide Ethiopian cohort. The V3 region was sequenced and the co-receptor tropism was predicted by the clinical and clonal models of the geno2pheno tool at different false positive rates (fpr) and for subtype. In an intention to treat analysis the impact of baseline tropism on outcome of antiretroviral therapy was evaluated. RESULTS: V3 loop sequencing was successful in 352 (84%) patients. HIV-1C was found in 350 (99.4%) and HIV-1A in two (0.6%) patients. When comparing the geno2pheno fpr10% clonal and clinical models, 24.4% predictions were discordant. X4-virus was predicted in 17.0 and 19.0%, respectively, but the predictions were concordant in only 6%. At fpr5%, concordant X4-virus predictions were obtained in 3.1%. The proportion of X4-tropic virus (clonal fpr10%) increased from 5.6 to 17.3% (p < 0.001) when 387 Ethiopian V3 loop sequences dated from 1984 to 2003 were compared with ours. In an intention to treat analysis, 67.9% reached treatment success at month 6 and only 50% at month 12. Only age and not tropism predicted therapy outcome and no difference was found in CD4+ cell gain between R5-tropic and X4-tropic infected patients. At viral failure, R5 to X4 switch was rare while X4 to R5 switch occurred more frequently (month 6: p = 0.006; month 12: p = 0.078). CONCLUSION: The HIV-1C epidemic is monophylogenetic in all regions of Ethiopia and R5-tropic virus dominates, even in patients with advanced immunodeficiency, although the proportion of X4-tropic virus seems to have increased over the last two decades. Geno2pheno clinical and clonal prediction models show a large discrepancy at fpr10%, but not at fpr5%. Hence further studies are needed to assess the utility of genotypic tropism testing in HIV-1C. In ITT analysis only age and not tropism influenced the outcome.

No association of cryptococcal antigenemia with poor outcomes among antiretroviral therapy-experienced HIV-infected patients in Addis Ababa, Ethiopia.

INTRODUCTION: There are limited data on clinical outcomes of ART-experienced patients with cryptococcal antigenemia. We assessed clinical outcomes of a predominantly asymptomatic, ART-experienced cohort of HIV+ patients previously found to have a high (8.4%) prevalence of cryptococcal antigenemia. METHODS: The study took place at All Africa Leprosy, Tuberculosis and Rehabilitative Training Centre and Black Lion Hospital HIV Clinics in Addis Ababa, Ethiopia. A retrospective study design was used to perform 12-month follow-up of 367 mostly asymptomatic HIV-infected patients (CD4<200 cells/µl) with high levels of antiretroviral therapy use (74%) who were previously screened for cryptococcal antigenemia. Medical chart abstraction was performed approximately one year after initial screening to obtain data on clinic visit history, ART use, CD4 count, opportunistic infections, and patient outcome. We evaluated the association of cryptococcal antigenemia and a composite poor outcome of death and loss to follow-up using logistic regression. RESULTS: Overall, 323 (88%) patients were alive, 8 (2%) dead, and 36 (10%) lost to follow-up. Among the 31 patients with a positive cryptococcal antigen test (titers ≥1∶8) at baseline, 28 were alive (all titers ≤1∶512), 1 dead and 2 lost to follow-up (titers ≥1∶1024). In multivariate analysis, cryptococcal antigenemia was not predictive of a poor outcome (aOR = 1.3, 95% CI 0.3-4.8). A baseline CD4 count <100 cells/µl was associated with an increased risk of a poor outcome (aOR 3.0, 95% CI 1.4-6.7) while an increasing CD4 count (aOR 0.1, 95% CI 0.1-0.3) and receiving antiretroviral therapy at last follow-up visit (aOR 0.1, 95% CI 0.02-0.2) were associated with a reduced risk of a poor outcome. CONCLUSIONS: Unlike prior ART-naïve cohorts, we found that among persons receiving ART and with CD4 counts <200 cells/µl, asymptomatic cryptococcal antigenemia was not predictive of a poor outcome.

Turn-over rate of academic faculty at the College of Health Sciences, Addis Ababa University: a 20-year analysis (1991 to 2011).

BACKGROUND: Faculty turn-over affects both workers and organizations. Turnover of faculty and researchers is increasing alarmingly and costing the universities and the country at large. Fast turnover of health professionals from the health system and from academic institutions has recently received substantial attention from both academia and health sector managers. This paper calculates the faculty turnover rate at the College of Health Sciences of Addis Ababa University during the period of September 1991 to August 2011. METHODS: The study was conducted at the College of Health Sciences, Addis Ababa University. Retrospective analysis of employee records was done. All records of the faculty that were working in the College during the 20-year period, starting from September 1991 to August 2011 were retrospectively reviewed. Data were collected from the employee records accessed from the College's human resources database and supplemented by payroll sheets and different reports. A structured checklist was used to extract the required data from the database. The crude turnover rate for academic faculty was calculated. RESULTS: Within the 20-year period of September 1991 to August 2011, a total of 120 faculty members left. The overall turn-over rate was 92.8 %. The rate in the most recent five years (172 %) is 8.5 times higher than the rate for the first five years (20 %). The average retention period before the termination of an employment contract was 4.9 years. The top five departments where employment contracts were relatively higher include: Nursing 15 (15.6 %), Internal Medicine 12 (12.5%), Public Health 10 (10.4%), Pediatrics 9 (9.4%) and Surgery 9 (9.4%). About two thirds (66.6%) of the faculty who were leaving were at the ranks of assistant professorship and above. CONCLUSION: This study revealed that outflow of faculty has been continuously increasing in the period reviewed. This implies that the College had been losing highly skilled professionals with considerably higher costs in monetary terms. In this regard, an urgent response is required to retain or significantly decrease the outflow of faculty. Different motivation and retention mechanisms should be identified and implemented. Various modalities of faculty development programs should also be initiated.

High prevalence of Cryptococcal antigenemia among HIV-infected patients receiving antiretroviral therapy in Ethiopia.

BACKGROUND: Cryptococcal disease is estimated to be responsible for significant mortality in Sub-Saharan Africa; however, only scarce epidemiology data exists. We sought to evaluate the prevalence of and risk factors for cryptococcal antigenemia in Ethiopia. METHODS: Consecutive adult HIV-infected patients from two public HIV clinics in Addis Ababa, Ethiopia were enrolled into the study. A CD4 count ≤ 200 cells/µl was required for study participation. Patients receiving anti-retroviral therapy (ART) were not excluded. A cryptococcal antigen test was performed for all patients along with an interview, physical exam, and medical chart abstraction. Logistic regression analysis was used to assess risk factors for cryptococcal antigenemia. RESULTS: 369 HIV-infected patients were enrolled; mean CD4 123 cells/µl and 74% receiving ART. The overall prevalence of cryptococcal antigenemia was 8.4%; 11% in patients with a CD4 count <100 cells/µl, 8.9% with CD4 100 to 150 cells/µl and 5.7% with CD4150-200 cell/µl. 84% of patients with cryptococcal antigenemia were receiving ART. In multivariable analysis, increasing age, self reported fever, CD4 count <100 cells/µl, and site of screening were associated with an increased risk of cryptococcal antigenemia. No individual or combination of clinical symptoms had optimal sensitivity or specificity for cryptococcal antigenemia. CONCLUSION: Cryptococcal antigenemia is high in Ethiopia and rapid scale up of screening programs is needed. Screening should be implemented for HIV-infected patients with low CD4 counts regardless of symptoms or receipt of ART. Further study into the effect of location and environment on cryptococcal disease is warranted.

Adverse drug reactions associated with antiretroviral treatment among adult Ethiopian patients in a tertiary hospital.

BACKGROUND: Adverse drug reactions (ADRs) are frequently encountered among patients taking Antiretroviral Treatment (ART). The aim of this study was to describe the type and frequency of ADRs among adult Ethiopians on ART. OBJECTIVE: to describe the type and frequency of short term adverse drug reactions among adult Ethiopian patients on ART at Tikur Anbessa teaching Hospital in Addis Ababa, Ethiopia. METHODS: From October 2008 to December 2009, 228 HIV positive patients were enrolled to a tertiary teaching hospital in Addis Ababa. Patients were closely monitored for ADRs for a median observation period of 18 weeks (79 total person-years of observation). Time-dependent occurrence of clinical adverse effects and abnormal laboratory values as defined by the AIDS Clinical Trial Group were analyzed (41). RESULTS: A total of 392 ARV drug related ADRs occurred Mild GI disturbances (36.8%) and headache (35.9%) were the most frequently reported symptoms. Thirty (7.7%) of the ADRs were severe requiring change or interruption of therapy (19 hematological and 11 hepatotoxic). Severe hematological complications were anemia (4.8%), neutropenia (2.6%) and thrombocytopenia (0.9%). Anemia occurred earl), in the first 4 weeks of ART treatment. Hepatic toxicity was also seen early but continued throughout the observation period, decreasing over time. Other ADRs encountered were grade I/II toxicities of rash, peripheral neuropathy, and metabolic disturbances. CONCLUSION AND RECOMMENDATIONS: ADRs occurred frequently in patients receiving ART. Grade III/IV toxicity that required withholding or change of treatment occurred in nearly 10% of the patients. Regular clinical, and laboratory monitoring appropriate to centers with limited resources need to be devised to monitor toxicity of ART Patient education on the easily recognizable ADRs could also reduce severe drug toxicities.

Prevalence of highly active antiretroviral therapy associated metabolic abnormalities and lipodystrophy in HIV infected patients.

BACKGROUND: Highly active antiretroviral therapy (HAART) improves the longevity of HIV patients. However, the side effect of the drugs leads to development of chronic metabolic and cardiovascular complications. OBJECTIVE: The aim of the study was to determine the prevalence and risk factors of the metabolic abnormalities and lipodystrophy among adult Ethiopian HIV infected patients on ART for one year and above. METHODS: A cross-sectional study was conducted among HIV infected patients on HAART for one year or more, attending the ART clinics of Tikur Anbessa Specialized hospital in Addis Ababa. A total of consecutive 356 HIV infected patients volunteered to participate in the study from July 2007 to January 2008. Data was collected using clinical interview technique on structured questionnaires and physical examination of the patient, 319 had biochemical tests performed. RESULTS: Three hundred fifty six HIV patients; 261 (73.1%) females and 95 (26%) males were studied. Two hundred nine (59.7%) patients were on Stavudine based and 135 (41.3%) were on Zidovudine based ART therapy. The overall prevalence of lipodystrophy was 68.3% (243), prevalence of hyperlipademia among 319 HIV patient was 56.9% Among these, the prevalence of hypercholesterolemia was 38.2%, high LDL cholesterol was 54.2% hypertryglyceredimeia was 15.2% Fasting hyperglycemia was 17.8% (IFG in 10.9% and overt diabetes in 6.9%). History of smoking was significantly associated with lipoatrophy and lipohypertrophy. ART regimen d4T was significantly associated with lipoatrophy. Duration of ART treatment > or = 1 yr was significantly associated with both lipoatrophy, lipohypertrophy and hypertriglyceredemia. CONCLUSIONS AND RECOMMENDATIONS: Lipodystrophies occurred in majority of patients on ART treatment for longer than one year, hyperlipaedemia and hyperglycaemia were also seen commonly in Ethiopian HIV patients on HAART. We recommend careful monitoring of metabolic abnormalities, examination of the patient for early detection of the side effect, change of the offending agents management of metabolic abnormalities.

Prevalence of oral and perioral manifestations in HIV positive adults at Tikur Anbessa Teaching Hospital Addis Ababa, Ethiopia.

BACKGROUND: Oral lesions are often characteristic in HIV patients and in the majority of cases can be diagnosed by their clinical features alone. To date there is no study addressing the prevalence of oral and perioral lesions in HIV patients in Ethiopia. OBJECTIVES: To assess prevalence of oral and perioral manifestations, the clinical symptoms of oral disease, and to assess the association of oral and perioral lesions to the socio- demographic status and CD4 count of ART naive HIV patients. METHODS: A cross-sectional study on 384 consecutive HIV patients before initiation of ARV treatment was conducted. Oral and perioral lesions were diagnosed according to the EC-clearinghouse's classification and diagnostic criteria for oral lesions in HIV infection and WHO collaborating centre on oral manifestations of HIV, 1992. RESULTS: One hundred and twenty six (32.8%) of the study subjects were males and 258 (67.2%) were females and mean age was 35.4 +/- 9.94 years (range of 14-84 years). Overall prevalence of oral lesions was 64.3%, and perioral lesions was 15.4%. Nearly half (44%) had dental caries. Pseudomembraneous candidiasis (20.1%), linear gingival erythema (11.7%), and erythematous candidiasis (9.1%) were the three most common HIV associated oral lesions. Angular cheilitis (8%) and molluscum contagiosum (4%) were the two most common perioral conditions. The most common oral symptoms reported were dry mouth (34.4%), difficulty eating (27.9%), and oral pain (27.3%). Oral symptoms and a CD4 count < 200 mm(-3) were significantly (X2 = 22.4, P = 0.0001) associated with presence of oral and perioral lesions. Age above 40 years (31%) was significantly associated with oral lesions (P = 0.016), but not with perioral lesions (P = 0.26). CONCLUSION: Oral and perioral lesions were common in HIV positive adults at Tikur Anbessa Specialized hospital and represent a treatable morbidity associated with this disease. Thus, a comprehensive oral examination is important in the clinical evaluation, management, and follow up of patients with HIV.

Morbidity and mortality of adult patients with HIV/AIDS at Tikur Anbessa Teaching Hospital, Addis Ababa, Ethiopia.

A one year (January 1-December 31, 2000) prospective study of consecutive HIV seropositive patients admitted to the medical wards to Tikur Anbessa Teaching Hospital was made to determine the morbidity, mortality, and spectrum of HIV-associated disease among medical inpatients. During the study period, there were 1813 medical admissions and 568 hospital deaths. Of the medical inpatients, 566 were tested for HIV-1 antibody because of clinical suspicion and for treatment decision. Of these, 237(42%) patients tested positive and this accounted for 13% of the annual medical admission. The male to female ratio was 1.4:1. The mean age +/- SD was 32.8 +/- 8.9 years with a range of 17-70 years. The mean length of hospital stay was 27.5 days (range: 0.5-103 days). Ninety two percent (218/237) of the patients were in WHO clinical stage IV at the time of hospital admission. Thirty one percent(73/237) of the patients died in hospital during the study period, accounting for 13%(73/568) of the annual hospital deaths among medical inpatients. Tuberculosis, central nervous system mass lesion suggestive of CNS toxoplasmosis, and sepsis were the three most common disease complexes among admissions and deaths. It is, therefore, recommended that similar studies estimating disease burden at different levels of health care system be made so as to assess the overall morbidity and mortality associated with HIV/AIDS in the country.