Infectious Diseases Institute (IDI)

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    Etiology of pruritic papular eruption with HIV infection in Uganda
    (American Medical Association., 200-12-01) Resneck, Jack S ; Beek, Marta Van ; Furmanski, Lisa ; Oyugi, Jessica ; LeBoit, Philip E. ; Katabira, Elly. ; Kambugu, Fred ; Maurer, Toby ; Berger, Tim ; Pletcher, Mark J. ; Machtinger, Edward L.
    Context A frequent cause of human immunodeficiency virus (HIV)–related morbidity in sub-Saharan Africa is a commonly occurring, intensely pruritic skin rash. The resulting scars are disfiguring and stigmatizing. Despite the substantial prevalence of pruritic papular eruption (PPE) among HIV-infected Africans, the cause has been elusive. Objective To determine the etiology of PPE occurring in HIV-infected individuals. Design, Setting, and Patients Cross sectional study of HIV-infected patients with active PPE from clinics in Uganda conducted from May 19 through June 6, 2003. Enrollment occurred in the month preceding May 19. Each participant was clinically examined by 2 dermatologists, had laboratory studies performed, was administered an epidemiologic questionnaire, and had a skin biopsy of a new lesion evaluated by a dermatopathologist. Main Outcome Measures Histological characteristics of new pruritic lesions. Other assessments included CD4 cell count, eosinophil count, and physician-assessed rash severity. Results Of 109 patients meeting inclusion criteria, 102 (93.6%) completed the study. The CD4 cell counts in this study population were generally low (median, 46/μL) and inversely related to increasing rash severity (median CD4 cell counts: 122 for mild, 41 for moderate, and 9 for severe; P .001 for trend). Eighty-six patients (84%; 95% confidence interval, 77%-91%) had biopsy findings characteristic of arthropod bites. Patients with arthropod bites on biopsy had significantly higher peripheral eosinophil counts (median, 330 vs 180/μL; P=.02) and had a trend toward lower CD4 cell counts (median, 40 vs 99/μL; P=.07) than those without histological evidence of arthropod bites. Conclusions Pruritic papular eruption occurring in HIV-infected individuals may be a reaction to arthropod bites. We hypothesize that this condition reflects an altered and exaggerated immune response to arthropod antigens in a subset of susceptible HIV-infected patients.
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    The academic alliance for AIDS care and prevention in Africa
    (The Johns Hopkins University AIDS Service, 2001-11) Quinn, Thomas C.
    In the continent of Africa, AIDS is the leading cause of death, responsible for over 20% of all fatalities. To date, over 16 million people in Africa have died from AIDS, and approximately 26 million or 70% of the world’s total of HIV infected people reside in sub-Saharan Africa. Howe ve r, little or no treatment, either for HIV infection itself or for its complications, is available to HIV infected Africans. This inequity in care between Africa and western countries has been attributed to lack of infrastructure, poverty, lack of financial support from developed countries, insufficient health care delivery systems, lack of knowledge by African physicians on the use of these drugs, insufficient laboratory support,political inaction, and many other factors. Although increasing attention has been focused on the problem, particularly in the lay press, and although pharmaceutical companies have reduced the cost of their drugs, most Africans still cannot afford these medicines, and little has been done to bring good clinical care to the millions of HIV infected Africans. To address this problem, a new organization was formed in June 2001 called "The Academic Alliance for AIDS Care and Prevention in Africa," led by a group of Ugandan physicians from Makerere University and the Infectious Diseases Society of America with HIV/AIDS care experts from North America.
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    Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting
    (Lippincott Williams & Wilkins, 2004) Oyugi, Jessica H. ; Byakika-Tusiime, Jayne ; Charlebois, Edwin D. ; Kityo, Cissy ; Mugerwa, Roy ; Mugyenyi, Peter ; Bangsberg, David R.
    Background: There are no validated measures of adherence to HIV antiretroviral therapy in resource-poor settings. Such measures are essential to understand the unique barriers to adherence as access to HIV antiretroviral therapy expands. Methods: We assessed correspondence between multiple measures of adherence and viral load suppression in 34 patients purchasing generic Triomune antiretroviral therapy (coformulated stavudine, lamivudine, and nevirapine; CIPLA, Ltd., Mumbai, India) in Kampala, Uganda. Measures included 3-day patient self-report, 30-day visual analog scale, electronic medication monitoring, and unannounced home pill count. HIV-1 load was determined at baseline and 12 weeks. Results: Mean adherence was 91%–94% by all measures. Seventysix percent of subjects had a viral load of<400copies/mLat12weeks. All measures were closely correlated with each other(R=0.77–0.89). Each measure was also significantly associated with 12-week HIV load. There was no significant difference between patient-reported and objective measures of adherence. Conclusions: This sample of patients purchasing generic HIV antiretroviral therapy has among the highest measured adherence reported to date. Patient-reported measures were closely associated with objective measures. The relative ease of administration of the 30-day visual analog scale suggests that this may be the preferred method to assess adherence in resource-poor settings.
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    Risk factors for and types of oesophageal cancer
    (The Lancet, 2004) Wabinga, H. R. ; Colebunders, B. ; Odida, M. ; Ocama, P. ; Colebunders, R.
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    Treatment of HIV/AIDS. Do the dilemmas only increase?
    (American Medical Association, 2004) Sande, Merle A. ; Ronald, Allan
    Physicians and other health care professionals who treat patients with human immunodeficiency virus (HIV)/AIDS are confronted daily with complex challenges. Fortunately, several articles in this theme issue of JAMA on HIV/AIDS help to increase the coping index for clinicians and researchers. The International AIDS Society-USA (IAS-USA) report in this issue represents a biennial update of the criterion standard for HIV care.1 Experts evaluated the research, conferred, integrated new information, graded the evidence basis for their decisions (an advance over their previous reports), and provided an up-to-date document that can serve as an evidence-based foundation for guiding HIV adult care in developed countries. These new guidelines have not changed dramatically but do reflect the contribution of new drugs and make more definite judgments about the most- effective regimens while remaining relatively consistent on when to start or to switch therapy.
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    The liver in HIV in Africa
    (International Medical Press, 2005) Feld, Jordan J. ; Ocama, Ponsiano ; Ronald, Allan
    As access to antiretroviral therapy improves across the African continent, liver disease is emerging as an important cause of morbidity and mortality among HIV-infected individuals. Although coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV), along with highly active antiretroviral therapy (HAART)- induced hepatotoxicity appear to be the major causes of liver disease in this population, other diseases endemic to Africa with hepatic manifestations are influenced by HIV infection as well. In this review we present the available data on liver disease in HIV-infected populations in Africa and discuss relevant data from the rest of the world. In addition, we highlight important areas for further study.
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    The International HIV Dementia Scale: a new rapid screening test for HIV dementia
    (Lippincott Williams & Wilkins, 2005) Sacktora, Ned C. ; Wong, Matthew ; Nakasujja, Noeline ; Skolasky, Richard L. ; Selnes, Ola A. ; Musisi, Seggane ; Robertson, Kevin ; McArthur, Justin C. ; Ronald, Allan ; Katabira, Elly
    Objective: HIV dementia is an important neurological complication of advanced HIV infection. The use of a cross-cultural screening test to detect HIV dementia within the international community is critical for diagnosing this condition. The objective of this study was to evaluate the sensitivity and specificity of a new screening test for HIV dementia, the International HIV Dementia Scale (IHDS) in cohorts from the US and Uganda. Design: Two cross-sectional cohort studies designed to evaluate for the presence of HIV dementia. Methods: Sixty-six HIV-positive individuals in the US and 81 HIV-positive individuals in Uganda received the IHDS and full standardized neurological and neuropsychological assessments. The sensitivity and specificity of varying cut-off scores of the IHDS were evaluated in the two cohorts. Results: In the US cohort, the mean IHDS score for HIV-positive individuals without dementia and with dementia were 10.6 and 9.3 respectively (P < 0.001). Using the cutoff of 10, the sensitivity and specificity for HIV dementia with the IHDS were 80% and 57% respectively in the US cohort, and 80% and 55% respectively in the Uganda cohort. Conclusions: The IHDS may be a useful screening test to identify individuals at risk for HIV dementia in both the industrialized world and the developing world. Full neuropsychological testing should then be performed to confirm a diagnosis of HIV dementia.
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    Rolling out antiretrovirals in Africa: there are still challenges ahead
    (Infectious Diseases Society of America, 2005-08) Colebunders, R. ; Ronald, A. ; Katabira, E. ; Sande, M.
    In their article “Lessons Learned from Highly Active Antiretroviral Therapy in Africa,” Akileswaran et al. [1] review the effectiveness of HAART programs in Africa. They report positive health outcomes, including high levels of treatment adherence and virological suppression that are comparable to those of industrialized countries [1]. Most of these studies, however, were performed in settings with significant external financial support, and the duration of patient follow-up was relatively short. Also, many of the studies are only currently available as abstracts, and as a result, a critical analysis of the strengths and weaknesses of the various programs is not possible. There is no doubt that the availability of antiretroviral drugs in Africa from the President’s Emergency Plan for AIDS Relief; the Global Fund for AIDS, Tuberculosis, and Malaria; and other donor programs is an extremely important life-saving initiative, especially when it is strategically linked to well-organized, community-based HIV-prevention programs. However, the challenge to roll out antiretrovirals in Africa to all those who need them and to obtain achievable long-term results is daunting. In this commentary, we detail some of these challenges.
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    Palliative care in sub-Saharan Africa
    ( 2005-08-13) Colebunders, Robert ; John, L ; Muganzi, A. ; Lynen, L. ; Kambugu, A.
    We agree with Richard Harding and Irene Higginson (June 4, p 1971) and Anne Merriman and Manjit Kaur (p 1909) that improving palliative care services for people living with HIV/AIDS in sub-Saharan Africa is extremely important despite the increasing access to antiretroviral treatment (ART). However, by far the most effective means of improving symptoms and the wellbeing of patients with AIDS is by successfully treating opportunistic infections and starting ART. With simple, affordable drugs and the free provision of antituberculous and antifungal therapy, most opportunistic infections can be cured. Numerous studies have shown the effectiveness of ART in Africa.3–5 We therefore agree with Merriman and Kaur’s view that palliative care in the era of ART should be clearly defined
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    Free antiretrovirals must not be restricted only to treatment-naive patients: experience in Uganda suggests that restricting access is not the way forward
    (Public Library of Science, 2005-10) Colebunders, Robert ; Kamya, Moses ; Semitala, Fred ; Castelnuovo, Barbara ; Katabira, Elly ; McAdam, Keith
    No Abstract
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    Tuberculosis immune reconstitution inflammatory syndrome in countries with limited resources
    (International Union Against Tuberculosis and Lung Disease, 2006) Colebunders, Robert ; John, L ; Huyst, V ; Kambugu, A ; Scano, F ; Lynen, L
    Mycobacterium tuberculosis infection accounts for probably one third of human immunodeficiency virus (HIV)related immune reconstitution inflammatory syndrome (IRIS) events, particularly in developing countries where HIV and tuberculosis (TB) co-infection is very common. Small cohort studies of HIV-positive patients with active TB treated with antiretroviral therapy (ART) suggest an incidence of TB IRIS varying between 11% and 45%.Risk factors for TB IRIS that have been suggested in certain studies but not in others include: starting ART within 6 weeks of starting TB treatment; extra-pulmonary or disseminated disease; a low CD4 lymphocyte count and a high viral load at the start of ART; and a good immunological and virological response during highly active antiretroviral therapy (HAART). It is important to agree on a clinical case definition of TB IRIS that could be used in resource-limited settings. Such a case definition could be used to determine the exact incidence and consequences of TB IRIS and would be valuable worldwide in clinical trials that are needed to answer questions on how this phenomenon could be prevented and treated.
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    Tuberculosis immune reconstitution inflammatory syndrome in countries with limited resources
    (International Union Against Tuberculosis and Lung Disease, 2006) Colebunders, Robert ; John, L. ; Huyst, V. ; Kambugu, Andrew ; Scano, F. ; Lynen, L.
    Mycobacterium tuberculosis infection accounts for probably one third of human immunodeficiency virus (HIV)related immune reconstitution inflammatory syndrome (IRIS) events, particularly in developing countries where HIV and tuberculosis (TB) co-infection is very common. Small cohort studies of HIV-positive patients with active TB treated with antiretroviral therapy (ART) suggest an incidence of TB IRIS varying between 11% and 45%.Risk factors for TB IRIS that have been suggested in certain studies but not in others include: starting ART within 6 weeks of starting TB treatment; extra-pulmonary or disseminated disease; a low CD4 lymphocyte count and a high viral load at the start of ART; and a good immunological and virological response during highly active antiretroviral therapy (HAART). It is important to agree on a clinical case definition of TB IRIS that could be used in resource-limited settings. Such a case definition could be used to determine the exact incidence and consequences of TB IRIS and would be valuable worldwide in clinical trials that are needed to answer questions on how this phenomenon could be prevented and treated.
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    A new model to monitor the virological efficacy of antiretroviral treatment in resource-poor countries
    (Elsevier, 2006) Colebunders, Robert ; Laurence, John ; Shihab, Hasan M. ; Semitala, Fred ; Lutwama, Fred ; Bakeera-Kitaka, Sabrina ; Lynen, Lut ; Spacek, Lisa ; Reynolds, Steven J. ; Quinn, Thomas C. ; Viner, Brant ; Mayanja-Kizza, Harriet ; Kamya, Moses, R.
    Monitoring the efficacy of antiretroviral treatment in developing countries is difficult because these countries have few laboratory facilities to test viral load and drug resistance. Those that exist are faced with a shortage of trained staff, unreliable electricity supply, and costly reagents. Not only that, but most HIV patients in resource poor countries do not have access to such testing. We propose a new model for monitoring antiretroviral treatment in resource-limited settings that uses patients’ clinical and treatment history, adherence to treatment, and laboratory indices such as haemoglobin level and total lymphocyte count to identify virological treatment failure, and offers patients future treatment options. We believe that this model can make an accurate diagnosis of treatment failure in most patients. However, operational research is needed to assess whether this strategy works in practice.
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    Measuring the outcomes of a comprehensive HIV care course: pilot test at the Infectious Diseases Institute, Kampala, Uganda
    (Lippincott Williams & Wilkins, 2006) Weaver, Marcia R ; Nakitto, Cecilia ; Schneider, Gisela ; Kamya, Moses R. ; Kambugu, Andrew ; Lukwago, Robinah ; Ronald, Allan ; McAdam, Keith ; Sande, Merle A.
    Objective: To evaluate the effects of the Infectious Diseases Institute’s 4-week course for African doctors on comprehensive management of HIV including antiretroviral therapy on four outcomes: (1) clinical skills, (2) clinical activities, (3) monitoring of HIV patients, and (4) training activities Design: Clinical exam at beginning and end of course and at followup 3 to 4 months later, and a cross-section telephone survey. Methods: Forty-seven doctors attending the course (October 2004, November 2004, March 2005, and April 2005) agreed to participate. A 17-item Clinical Exam Checklist was used to assess clinical skills. A telephone survey was conducted 1 month after the course to collect data in four areas: clinical activities, monitoring of HIV patients, case studies on initiation of ART, and training activities. Results: The course improved the clinical skills of doctors. Between the beginning and end of the course, their clinical skills improved significantly in 11 of 17 areas (n = 34). Between the end of the course and follow-up, their skills improved significantly in three areas (n = 14). The trainees were practicing HIV care and training. The telephone survey (n = 46) showed that 93% of trainees treated HIV patients, 35% provided training on HIV, and 47% monitored the weight of the last HIV patient treated (patient’s weight was a clinical end point to measure health status). At follow-up, everyone provided training and trained an average of 20 people per month.
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    Prevalence, incidence and predictors of severe anaemia with zidovudine-containing regimens in African adults with HIV infection within the DART trial
    (International Medical Press, 2006) Ssali, Francis ; Stöhr, Wolfgang ; Munderi, Paula ; Reid, Andrew ; Walker, A Sarah ; Gibb, Diana M. ; Mugyenyi, Peter ; Kityo, Cissy ; Grosskurth, Heiner ; Hakim, James ; Byakwaga, Helen ; Katabira, Elly ; Darbyshire, Janet H. ; Gilks, Charles F.
    Objective: To describe the prevalence, incidence and predictors of severe anaemia in previously untreated symptomatic HIV-infected adults with CD4+ T-cells <200 cells/mm3 initiating zidovudine-containing regimens in Africa. Design: DART is a randomized trial comparing two strategies for HIV/AIDS management in Uganda and Zimbabwe. Methods: We analysed the occurrence of anaemia at weeks 4 and 12, and then every 12 weeks. We also evaluated sex, age, WHO stage, body mass index (BMI), baseline laboratory measurements and first regimen as predictors of developing grade 4 anaemia (<6.5 mg/dl) by week 48 using logistic regression. Results: To May 2005, 3,314 participants (65% women, 23% at WHO stage 4, median age=37 years, baseline CD4+ T-cell=86 cells/mm3 and median baseline haemoglobin= 11.4 g/dl) had a median 72 weeks follow-up. Prevalence of grade 4 anaemia was 0.7%, 2.0%, 0.5% and <0.5% at weeks 4, 12, 24 and ≥36, respectively. Overall, 219 (6.6%) participants developed grade 4 anaemia by week 48; women and those with lower haemoglobin, CD4+ T-cell count and BMI at baseline were at significantly higher risk (P<0.05), but not those with lower neutrophils or receiving cotrimoxazole at baseline. Conclusions: We observed a higher incidence of grade 4 anaemia than in studies from industrialized countries, which is likely to be due in part to population characteristics and in part to a higher rate of concurrent HIV-related clinical events. Clinical vigilance and haemoglobin measurements 4, 8 and 12 weeks after starting zidovudine could help to manage serious anaemia.
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    Laboratory medicine in Africa: a barrier to effective health care
    (University of Chicago Press, 2006) Petti, Cathy A ; Polage, Christopher R ; Quinn, Thomas C. ; Ronald, Allan R. ; Sande, Merle A.
    Providing health care in sub-Saharan Africa is a complex problem. Recent reports call for more resources to assist in the prevention and treatment of infectious diseases that affect this population, but policy makers, clinicians, and the public frequently fail to understand that diagnosis is essential to the prevention and treatment of disease. Access to reliable diagnostic testing is severely limited in this region, and misdiagnosis commonly occurs. Understandably, allocation of resources to diagnostic laboratory testing has not been a priority for resource-limited health care systems, but unreliable and inaccurate laboratory diagnostic testing leads to unnecessary expenditures in a region already plagued by resource shortages, promotes the perception that laboratory testing is unhelpful, and compromises patient care. We explore the barriers to implementing consistent testing within this region and illustrate the need for a more comprehensive approach to the diagnosis of infectious diseases, with an emphasis on making laboratory testing a higher priority.
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    HIV Eosinophilic Folliculitis in Uganda
    (American Medical Association (AMA), 2006) Colebunders, Robert ; Castelnuovo, Barbara ; Byakwaga, Hellen
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    Are the best antiretrovirals being used in Africa?
    (Mediscript Limited, 2006) John, Laurence ; Kambugu, Andrew ; Songa, Patricia ; castelnouvo, Barbara ; Colebunders, Robert ; Kamya, Moses
    No Abstract
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    When to switch for antiretroviral treatment failure in resource-limited settings?
    (Lippincott Williams & Wilkins., 2007) Vekemansa, Marc ; Johnb, Laurence ; Colebunders, Robert
    Thanks to the leadership of the World Health Organisation (WHO), and massive financial support from programmes such as the Global Fund and the US President’s Emergency Plan for AIDS Relief (PEPFAR), the number of HIV-infected individuals accessing antiretroviral therapy (ART) in resource-limited settings has tripled from 2001 to 2005. An estimated 1.3 million HIV-infected individuals were on ART in 2005, representing 20% of those in need of treatment.
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    Symptomatic hyperlactatemia associated with nucleoside analogue reverse-transcriptase inhibitor use in HIV-infected patients: a report of 24 cases in a Resource-Limited Setting (Uganda).
    (University of Chicago Press, 2007) Songa, Patricia Mwebaze ; Castelnuovo, Barbara ; Mugasha, Estella Birabwa ; Ocama, Ponsiano ; Kambugu, Andrew
    We describe 24 Ugandan patients with human immunodeficiency virus infection who developed symptomatic hyperlactatemia associated with the use of nucleoside analogues. All patients were receiving combination therapy that contained stavudine. The median serum lactate level was 6.6 mmol/L. All patients had their antiretroviral treatment regimen discontinued. Hospital admission was required for 5 patients. Five patients died.