Does tuberculosis accelerate the progression of HIV disease? Evidence from basic science and epidemiology.
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Disease Progression↗
Biomedical subjects
K M De Cock
Publications and source records attributed to K M De Cock.
Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.
BACKGROUND: There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS: Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS: Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION: In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.
AIDS-Related Opportunistic Infections↗
Lack of protection against HIV-1 infection among women with HIV-2 infection.
OBJECTIVE: To assess whether HIV-2 infection protects against HIV-1 infection by comparing the rate of HIV-1 seroconversion among HIV-negative and HIV-2-seropositive women followed in a cohort study in Abidjan, Côte d'Ivoire. DESIGN: Prospective cohort study METHODS: HIV seroconversion was assessed in 266 HIV-seronegative, 129 HIV-1-seropositive, and 127 HIV-2-seropositive women participating in a closed cohort study of mother-to-child transmission of HIV conducted during 1990-1994. Participants were seen every 6 months, and blood samples were obtained. All blood samples were screened for HIV antibodies by enzyme immunoassay (EIA) and confirmed by line immunoassay (LIA) and Western blot. Among women who were HIV-seronegative at enrolment, seroconversion was defined as new EIA-reactivity confirmed on LIA and Western blot. Among HIV-1- or HIV-2-seropositive women, seroconversion to dual reactivity was defined as new dual reactivity on the LIA that was confirmed by reactivity on both HIV-1- and HIV-2-monospecific EIA. RESULTS: Five HIV-seronegative women became HIV-1-seropositive [seroconversion rate, 1.1 per 100 person-years; 95% confidence interval (CI), 0.3-2.5), and none became HIV-2-seropositive. No HIV-1-seropositive women became HIV-1/2 dually reactive, whereas six HIV-2-seropositive women acquired HIV-1 seroreactivity and thus became HIV-1/2 dually reactive (seroconversion rate 2.9 per 100 person-years; 95% CI, 1.1-6.3). HIV-2-seropositive women were more likely to acquire HIV-1 seroreactivity than were HIV-seronegative women (rate ratio, 2.7; 95% CI, 0.7-11.2), but this difference was not statistically significant (P>0.15). CONCLUSION: HIV-2 infection does not appear to protect against HIV-1 infection.
Adolescent↗
Risk factors for pulmonary mycobacterial disease in South African gold miners. A case-control study.
Pulmonary mycobacterial disease is common in miners. Risk factors for nontuberculous pulmonary mycobacterial (NTM) disease and tuberculosis (TB) in gold miners were identified in a retrospective case-control study that included 206 NTM patients and 381 TB patients of known human immunodeficiency virus (HIV) status diagnosed between 1993 and 1996. A total of 180 HIV-tested trauma/surgical inpatients were selected as control patients. Both HIV infection (odds ratio [OR] 3.6 for NTM and 4.5 for TB patients) and higher grades of silicosis (OR 5.0 for NTM and 4.9 for TB patients) were significantly more common in NTM and TB patients than in control patients. HIV prevalence rose in the control and both case groups during the study period. The overall HIV prevalence was 13.1% in NTM patients, 14.2% in TB patients, and 5.6% in control patients. Previous TB (OR 9.6), premorbid focal radiological scarring (OR 7.4) and a dusty job at diagnosis (OR 2.4) were additional significant risk factors for NTM disease. These findings suggest that the historically high incidence of NTM disease in miners is largely attributable to chronic chest disease from silica dust inhalation and prior TB. HIV infection has recently become an additional risk factor for mycobacterial disease in miners and is likely to become increasingly important as the HIV epidemic progresses.
Adult↗
The impact of HIV infection on Mycobacterium kansasii disease in South African gold miners.
The impact of human immunodeficiency virus (HIV) infection on Mycobacterium kansasii disease in miners was investigated with a retrospective study covering a single workforce. M. kansasii, isolated from 43 HIV-positive and 202 HIV-negative miners, was the most common nontuberculous mycobacterial (NTM) species in both HIV groups. CD4 counts were unusually high for M. kansasii disease (mean 490 x 10(6)/L, from 14 HIV-positive men). Treatment outcomes were similar: mortality during treatment was higher in HIV-positive than in HIV-negative men (9% and 2%, respectively), but not significantly so. The majority of a sample of 31 HIV-positive and 92 HIV-negative men had radiological silicosis and/or old tuberculosis scarring prior to M. kansasii disease. A normal premorbid radiograph was more common in HIV-positive men (45% versus 24%; odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.01 to 6.67). New cavitation was less common (55% versus 78%; OR, 0.34; 95% CI, 0.13 to 0.88) and new hilar adenopathy more common (OR, 5.07; 95% CI, 1.24 to 21.9) in HIV-positive than in HIV-negative men. Miners, who have additional NTM risk factors, develop M. kansasii disease that occurs at an earlier stage of HIV infection and more closely resembles disease in HIV-negative men than has been found for HIV-associated M. kansasii disease in other settings.
AIDS-Related Opportunistic Infections↗
Nontuberculous mycobacteria: defining disease in a prospective cohort of South African miners.
A gold mining work force was followed prospectively over 1 yr for sputum nontuberculous mycobacterial (NTM) isolates. NTM were isolated from 118 men, of whom 32 (27%) met the American Thoracic Society (ATS) case-definitions for pulmonary NTM disease (23 M. kansasii, seven M. scrofulaceum, one M. avium, and one M. abscessus). Determining isolate significance was difficult because most men had been started on presumptive TB treatment before isolate identification (70%). Histologic criteria were considered inappropriate for this high M. tuberculosis incidence population, particularly for patients who had stabilized on presumptive TB treatment. Among men not meeting case-definitions, indicators of disease were significantly more prevalent for M. kansasii than for M. fortuitum, the local laboratory contaminant (ORs: 6.5 for cough, 7. 2 for smear-positivity, 36.0 for radiologic changes, and 14.3 for presumptive TB treatment), suggesting underdiagnosis of M. kansasii disease. Of 53 men with definite or possible M. kansasii disease, 18 (34%) were HIV-positive. HIV-associated M. kansasii disease occurred at an early stage of immunosuppression (median CD4 count, 381 x 10(6)/L) with a good outcome (83% cured after 12 mo of treatment). ATS case-definitions for NTM disease are difficult to apply in this population, and treatment decisions should be guided by the pathogenic potential of the isolate.
Adult↗
Use of miniradiographs to detect silicosis. Comparison of radiological with autopsy findings.
Radiological and routine autopsy findings from 241 South African gold miners were compared, using pathology as the "gold standard." Previous annual screening miniradiographs were read independently by two readers, using the International Labor Office (ILO) grading system, without reference to personal identifiers. Individual and consensus silicosis grades were recorded for each subject. When pathological and radiological silicosis were defined as any abnormal grade, the sensitivity and specificity of the radiological diagnosis was 67.5% and 80%, with positive and negative predictive values of 63% and 83%. Most undetected autopsy silicosis was early-grade. Using higher pathological and radiological grades to define silicosis (5 nodules or more and ILO grades 1/1 and above), sensitivity and specificity increased to 71% and 96%, and positive and negative predictive values increased to 76% and 95%, respectively. Use of a consensus grade made little difference to results from individual readers. For each radiological definition, sensitivity was considerably higher than, but specificity was similar to, that found in a previous study of South African gold miners which used the same pathology source and standard sized films. The difference between these two study findings, and unexpected demonstration of higher sensitivity from miniradiographs, suggests that further research is required into factors affecting radiological interpretation before silicosis grading can be considered to be adequately standardized.
Adult↗
Risk of cancer in patients with HIV disease. London African HIV/AIDS Study Group.
The aim of this study was to compare cancer incidence in a cohort of HIV-infected patients with the incidence rates in the population of South East England. Data collected for a retrospective cohort study of 2048 HIV-infected patients were analysed to examine the incidence of cancer. Cases of cancer occurring in South East England from 1985-1995 were obtained from the Thames Cancer Registry. Standardized incidence ratios were calculated by comparison of the observed number of cases for each cancer type in HIV-infected non-Africans with the numbers expected, calculated from the age and sex specific registration rates for the South East England population using person-years of observation. The crude incidence rates of cancer were calculated for HIV-infected Africans. The incidence of non-AIDS defining cancers such as Hodgkin's disease (standardized incidence ratio 22; 95% CI: 3-80) and anal cancer (standardized incidence ratio 125; 95% CI: 3-697) were significantly increased for non-African males with HIV disease. Anal cancer was also significantly increased for non-African females (standardized incidence ratio 1667; 95% CI: 43-9287). Kaposi's sarcoma (KS) was the commonest cancer among HIV-infected Africans and males had an incidence which was nearly 3 times that of females. There is evidence to suggest that the risks for other non-AIDS defining cancers were significantly increased in persons with HIV disease which may have implications for HIV/AIDS surveillance.
Adult↗
DOTS and drug resistance: a silver lining to a darkening cloud.
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Antitubercular Agents↗
Risk factors for tuberculosis in patients with AIDS in London: a case-control study.
OBJECTIVE: To identify risk factors for the acquired immune-deficiency syndrome (AIDS) associated with tuberculosis, in patients with AIDS attending 11 of the largest human immunodeficiency virus (HIV)/AIDS Units in London. DESIGN: Case-control study nested in a retrospective cohort of 2048 HIV-1 positive patients. Cases were defined as patients with a definitive diagnosis of tuberculosis, and controls as patients with AIDS and without tuberculosis during follow-up. RESULTS: Of 627 patients diagnosed with AIDS, 121 had a definitive diagnosis of tuberculosis. Significant risk factors for tuberculosis in the univariate analysis were sex, ethnicity, age, HIV exposure category and hospital attended, and in the multiple regression analysis ethnicity, age and hospital attended. African ethnicity was the strongest risk factor for tuberculosis (adjusted odds ratio [AOR] 5.9, 95% confidence interval 3.4-10.2). The risk of tuberculosis was higher in the younger age groups (test for trend P < 0.001). The hospital-associated risk of tuberculosis was more heterogeneous in the non-African group, and non-Africans attending Hospital 1 had an increased risk of tuberculosis which was statistically significant. CONCLUSIONS: The risk factors for AIDS-associated tuberculosis in London are sub-Saharan African origin, younger age group, and, among the non-Africans only, attending one hospital in east London. Different transmission patterns and mechanisms for the development of tuberculosis may operate in different settings depending on the background risk of tuberculous infection. Screening for tuberculosis infection and disease among HIV-positive individuals in London is important for the provision of preventive or curative therapy, and prophylaxis policies need to be designed in accordance with the transmission patterns and mechanisms of disease.
Acquired Immunodeficiency Syndrome↗
Will DOTS do it? A reappraisal of tuberculosis control in countries with high rates of HIV infection.
In 1993 the WHO declared tuberculosis a global emergency, and subsequently introduced the DOTS strategy, a technical and management package based on earlier work of the IUATLD and international experience with directly observed therapy. Despite successful implementation of most of the elements of this strategy in several African countries and settings, tuberculosis case rates continue to escalate where the prevalence of HIV infection is high. We explore possible reasons for the failure to control tuberculosis even in the context of tuberculosis programmes that have been considered models for others to emulate. In many African countries half or more of tuberculosis patients are now HIV-infected; in such settings, the overall epidemiology of tuberculosis is disproportionately affected by what happens in the HIV-infected subpopulation of the community. Persons with HIV infection are at increased risk of rapid progression following primary infection or re-infection, and also from reactivation of latent infection with Mycobacterium tuberculosis. More intensive strategies need to be targeted to the HIV-infected to interrupt on-going transmission (active and passive case detection; prevention of nosocomial transmission) and reactivation (preventive therapy). The high burden of other HIV-related disease in patients with tuberculosis, such as other bacterial infections, toxoplasmosis and other manifestations of AIDS, require that tuberculosis programmes integrate their activities better with those of HIV/AIDS programmes, including those for provision of HIV/AIDS care. Enhanced epidemiological surveillance is required to follow tuberculosis trends in the HIV-positive and negative sub-populations of communities, which may respond differently to control efforts. Strategies for tuberculosis control programmes in countries of high and low HIV prevalence cannot be the same, but must take into account the epidemiology of HIV infection. HIV/AIDS in Africa poses severe challenges of purpose and identity to tuberculosis control programmes, which have not adapted to the altered realities of the HIV/AIDS era. DOTS alone is unlikely to control tuberculosis in sub-Saharan Africa; one major achievement of DOTS when implemented, however, has been its apparent ability to limit the development and spread of drug resistance.
AIDS-Related Opportunistic Infections↗
Mycobacterium kansasii and M. scrofulaceum isolates from HIV-negative South African gold miners: incidence, clinical significance and radiology.
SETTING: A South African gold mining hospital. OBJECTIVE: To investigate the clinical significance of non-tuberculous mycobacteria (NTM) isolates, and estimate NTM disease incidence in human immunodeficiency virus (HIV) negative miners. DESIGN: Retrospective case series describing clinical and radiological features associated with NTM sputum isolates from HIV-negative miners between January 1993 and July 1996, and a comparison group with Mycobacterium tuberculosis infection. RESULTS: Of miners with NTM isolates, 90% had been HIV-tested and 81% were HIV-negative. M. kansasii and M. scrofulaceum accounted for 202 (68%) and 41 (14%) isolates respectively. More than 80% of miners with M. kansasii or M. scrofulaceum were smear positive, and new cavitation was present in 78% and 74% respectively. Treatment failure occurred in 3% of M. kansasii and 12% of M. scrofulaceum patients. A normal pre-morbid radiograph was significantly less common in NTM than M. tuberculosis patients (odds ratio 0.26 and 0.10 for M. kansasii and M. scrofulaceum, respectively). NTM disease incidence, defined as NTM isolate plus new cavitation, was estimated at 66 and 12 per 100000 person-years for M. kansasii and M. scrofulaceum, respectively. CONCLUSIONS: M. kansasii and M. scrofulaceum disease are common in HIV-negative South African gold miners. Most isolates are associated with new cavitation against a background of silicosis or old TB scarring.
Adult↗
Mycobacterial disease in South African gold miners in the era of HIV infection.
SETTING: Mining company tuberculosis (TB) clinic, Freestate Province, South Africa. OBJECTIVES: To investigate the impact of the human immunodeficiency virus (HIV) on tuberculosis case rates and case detection methods in miners. DESIGN: Demographic and clinical data were extracted from the central computerised TB database for the period 1990-1996. RESULTS: A total of 7450 miners had TB, which was smear- or culture-positive in 81% of pulmonary cases. Incidence rates more than doubled between 1990 and 1996, from 1174 to 2476 per 100000 per year. Non-tuberculous mycobacteria, predominantly Mycobacterium kansasii, were isolated more commonly from retreatment than from new cases (19.5% and 11.5% respectively, P < 0.001). HIV prevalence in TB patients increased from 15% in 1993 to 45% in 1996 (P < 0.001). There was no significant association between HIV and smear status, but HIV-positive patients were more likely than HIV-negative patients to present passively with symptoms rather than through the active radiological screening programme (OR 1.9, P < 0.0001). The overall proportion of patients presenting passively increased from 23% in 1990 to 51% in 1996 (P < 0.001). CONCLUSION: The HIV epidemic has lead to increased TB incidence in South African miners to very high rates, and appears to be impacting on the efficacy of the active radiological screening programme.
Adult↗
Disease progression and survival in HIV-1-infected Africans in London.
OBJECTIVE: To examine differences in progression to AIDS and death between HIV-1-positive Africans (most infected in sub-Saharan Africa and therefore with non-B subtypes) and HIV-1-positive non-Africans in London. DESIGN: Retrospective cohort study of 2048 HIV-1-positive individuals. SETTING: HIV-1-infected individuals attending 11 of the largest HIV/AIDS units in London. PATIENTS: Subjects were 1056 Africans and 992 non-Africans seen between 1982-1995. RESULTS: There were no differences in crude survival from presentation to death between Africans and non-Africans (median 82 and 78 months, respectively; P = 0.22). Africans progressed more rapidly to AIDS [hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.02-1.45] but after adjustment for age, sex, Centers for Disease Control and Prevention category B symptoms and CD4+ lymphocyte count at presentation, year of HIV diagnosis and hospital attended, this difference was no longer significant (adjusted HR, 1.15; 95% CI, 0.93-1.43). Africans with AIDS had a reduced risk of death compared with non-Africans (HR, 0.78; 95% CI, 0.63-0.96) but not after adjustment for age, CD4+ lymphocyte count at AIDS, initial AIDS-defining conditions (ADC) and hospital attended (HR, 0.98; 95% CI, 0.76-1.27). Tuberculosis as the first ADC was associated with a 64% reduction in the risk of death. CD4+ lymphocyte decline was not significantly different between Africans and non-Africans (P = 0.18). CONCLUSIONS: Differences in progression to AIDS and death and CD4+ lymphocyte decline between HIV-1-infected Africans and non-Africans in London could not be attributed to ethnicity or different viral subtypes. Age and the clinical and immunological stage at presentation, or AIDS, were the major determinants of outcome. Compared with other diagnoses, tuberculosis as the initial ADC was associated with increased survival. Lack of access to health care and exposure to environmental pathogens are the most likely causes of reduced survival with AIDS in Africa, rather than inherently different rates of progression of immune deficiency due to racial differences or viral subtypes.
Acquired Immunodeficiency Syndrome↗
Disease progression and survival following specific AIDS-defining conditions: a retrospective cohort study of 2048 HIV-infected persons in London.
OBJECTIVE: To assess the impact of specific AIDS-defining conditions on survival in HIV-infected persons, with emphasis on the effect of tuberculosis. METHODS: A retrospective cohort analysis of HIV-infected Africans and non-Africans attending 11 specialist HIV/AIDS units in London enrolled for a comparison of the natural history of HIV/AIDS in different ethnic groups. RESULTS: A total of 2048 patients were studied of whom 627 (31%) developed 1306 different AIDS indicator diseases. Pneumocystis carinii pneumonia accounted for 159 (25%) of initial AIDS episodes and tuberculosis for 103 (16%). In patients with HIV disease, tuberculosis had the lowest risk [relative risk (RR), 1.11; 95% confidence interval (CI), 0.75-1.63], and high-grade lymphoma had the highest risk (RR, 20.56; 95% CI, 2.70-156.54) for death. For patients with a prior AIDS-defining illness, the development of subsequent AIDS indicator diseases such as Pneumocystis carinii pneumonia (RR, 1.18; 95% CI, 0.77-1.83) and tuberculosis (RR, 1.36; 95% CI, 0.76-2.47) had the best survival, and non-Hodgkin's lymphoma had the worst survival (RR, 9.67; 95% CI, 1.26-74.33). Patients with tuberculosis had a lower incidence of subsequent AIDS-defining conditions than persons with other initial AIDS diagnoses (rate ratio, 0.47; 95% CI, 0.37-0.59). CONCLUSIONS: Considerable variation exists in the relative risk of death following different AIDS-defining conditions. The development of any subsequent AIDS-defining condition is associated with an increased risk of death that differs between diseases, and this risk should be considered when evaluating the impact of specific conditions. Like other AIDS-defining conditions, incident tuberculosis was associated with adverse outcome compared with the absence of an AIDS-defining event, but we found no evidence of major acceleration of HIV disease attributable to tuberculosis.
AIDS-Related Opportunistic Infections↗
The Côte d'Ivoire national HIV counseling and testing program for tuberculosis patients: implementation and analysis of epidemiologic data.
OBJECTIVES: To describe the implementation of a free, voluntary and confidential HIV counseling and testing program for patients with newly diagnosed tuberculosis at the eight large outpatient tuberculosis centers in Côte d'Ivoire, and to present epidemiologic findings on participating patients. DESIGN: HIV counseling and testing program with ongoing HIV serosurveillance. METHODS: HIV counseling and testing services were established at the two tuberculosis centers in Abidjan in 1989 and were extended to six centers in the Côte d'Ivoire interior in the first half of 1994. Characteristics of counseled patients, acceptance rates of HIV testing, and HIV serologic results were analyzed for all eight centers from 1994 to 1996. Temporal trends in HIV seropositivity rates were examined for the two centers of Abidjan from 1989 to 1996. RESULTS: From July 1994 through December 1996, 17 946 (91.8%) out of 19 594 patients who were counseled at the eight centers in Côte d'Ivoire consented to HIV testing, of whom 7749 (43.2%) were HIV-seropositive. The highest rates of 47.0 and 45.6% were found in the two centers in Abidjan, with rates ranging from 32.9 to 42.4% in the six centers in the interior. HIV-seropositive tuberculosis patients from each of the 50 districts in Côte d'Ivoire were identified. In Abidjan, the HIV seropositivity rate remained relatively stable among men (46.7% in 1989, 48.5% in 1991, 43.6% in 1996), but rose sharply among women from 32.7% in 1989 to 50.1% in 1996. CONCLUSIONS: The high HIV seropositivity rates among tuberculosis patients in all geographic regions of Côte d'Ivoire indicate that the HIV epidemic has now spread throughout the country. However, the successful implementation of an extensive HIV counseling and testing program for more than 37000 tuberculosis patients to date demonstrates the commitment of the Côte d'Ivoire Ministry of Health to integrating HIV/AIDS prevention activities with tuberculosis control efforts. When logistically and economically feasible, the extension of HIV-related social and clinical services to HIV-seropositive tuberculosis patients should be considered by other national tuberculosis control programs in Africa.
AIDS Serodiagnosis↗
From exceptionalism to normalisation: a reappraisal of attitudes and practice around HIV testing.
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Anonymous Testing↗
The growing challenge of HIV/AIDS in developing countries.
The burden of HIV infection and disease continues to increase in many developing countries. An emerging theme is of an HIV pandemic composed of mini-epidemics, each with its own characteristics in terms of the trends in HIV prevalence, those affected, and the HIV-related opportunistic diseases observed. A number of explanations for the observed differences in the spread of HIV infection have been proposed but since the factors concerned, such as sexual behaviour and the prevalence of other sexually transmitted diseases, are closely interrelated, it is difficult to tease out which are the most important. Among HIV-related opportunistic diseases, tuberculosis stands out as the most important cause of morbidity and mortality in most developing countries, but the relative prevalence of other diseases shows considerable regional variation. Thus, there is a need for local approaches to the global problem of managing HIV disease. The most pressing public health challenges are to use existing knowledge of strategies to reduce HIV transmission, and to apply them in ways appropriate to the local situation, and to develop, evaluate and implement interventions to prolong healthy life in those already infected.
AIDS-Related Opportunistic Infections↗