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Biomedical subjects

Stephen D Lawn

Publications and source records attributed to Stephen D Lawn.

At least 19 recordsLinked to original sources
PubMed2006

Short-term risk of AIDS or death in people infected with HIV-1 before antiretroviral therapy in South Africa: a longitudinal study.

BACKGROUND: In sub-Saharan Africa, data for short-term risk of AIDS or death, which might inform decisions about when to start antiretroviral therapy (ART), are scarce. Our aim was to investigate these risks in patients who had no access to ART or who were given zidovudine alone. METHODS: 6-month risks (%) of death, AIDS, and combined risk of AIDS and death (AIDS/death) were calculated according to CD4-cell count category of less than 200 cells per microL, 200-350 cells per microL, or greater than 350 cells per microL, stratified by WHO clinical stages 1 and 2 combined, 3, or 4 in untreated patients (n=1399) seeking care in tertiary public-sector HIV clinics before widespread availability of ART in Cape Town, South Africa. FINDINGS: Risk of death for WHO stages 1 and 2 was 3.5% for those with less than 200 cells per microL, 2.8% for 200-350 cells per microL, and 1.2% for greater than 350 cells per microL. The corresponding rates for WHO stage 3 were 10.8%, 4.3%, and 4.9% and for stage 4, 22.2%, 10.3%, and 13.8%. 52% (90) of deaths took place in patients without AIDS. 6-month risk of AIDS for WHO stages 1 and 2 was 3.5% for those with less than 200 cells per microL, 1.6% for 200-350 cells per microL, and zero for greater than 350 cells per microL. The corresponding rates for those with WHO stage 3 disease were 17.4%, 7.0%, and 2.2%. INTERPRETATION: In this study, risk of AIDS in patients with a CD4-cell count of less than 200 cells per microL or greater than 350 cells per microL was similar to that previously reported from European cohorts, but was 1.9 times greater for those with CD4-cell counts of between 200 and 350 cells per microL. The high death rate before development of AIDS and a high risk of AIDS in those with CD4-cell counts of 200-350 cells per microL indicate that delay in initiation of ART is associated with increased morbidity and mortality. These findings might help to amend criteria for start of ART in resource-limited settings.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control.

BACKGROUND: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program. METHODS: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register. RESULTS: Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals. CONCLUSIONS: PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals.

Adolescent↗
PubMed2006

Determinants of mortality and nondeath losses from an antiretroviral treatment service in South Africa: implications for program evaluation.

BACKGROUND: The scale-up of antiretroviral treatment (ART) services in resource-limited settings requires a programmatic model to deliver care to large numbers of people. Understanding the determinants of key outcome measures--including death and nondeath losses--would assist in program evaluation and development. METHODS: Between September 2002 and August 2005, all in-program (pretreatment and on-treatment) deaths and nondeath losses were prospectively ascertained among treatment-naive adults (n=1235) who were enrolled in a community-based ART program in South Africa. RESULTS: At study censorship, 927 patients had initiated ART after a median of 34 days after enrollment in the program. One hundred twenty-one (9.8%) patients died. Mortality rates were 33.3 (95% CI, 25.5-43.0), 19.1 (95% CI, 14.4-25.2), and 2.9 (95% CI, 1.8-4.8) deaths/100 person-years in the pretreatment interval, during the first 4 months of ART (early deaths), and after 4 months of ART (late deaths), respectively. Pretreatment and early treatment deaths together accounted for 87% of deaths, and were independently associated with advanced immunodeficiency at enrollment. Late deaths were comparatively few and were only associated with the response to ART at 4 months. Nondeath program losses (loss to follow-up, 2.3%; transfer-out, 1.9%; relocation, 0.7%) were not associated with immune status and were evenly distributed during the study period. CONCLUSIONS: Loss to follow-up and late mortality rates were low, reflecting good cohort retention and treatment response. However, the extremely high pretreatment and early mortality rates indicate that patients are enrolling in ART programs with far too advanced immunodeficiency. Causes of late access to the ART program, such as delays in health care access, health system delays, or inappropriate treatment criteria, need to be addressed.

Adult↗
PubMed2006

Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control.

OBJECTIVES: To determine burden and risk factors for tuberculosis (TB) in an antiretroviral treatment (ART) programme and its impact on ART outcomes. DESIGN: Prospective cohort study. METHODS: Prevalent TB was assessed at baseline and incident TB was ascertained prospectively over 3 years among 944 patients accessing a community-based ART programme in South Africa. RESULTS: At enrollment, median CD4 cell count was 96 cells/microl and 52% of patients had a previous history of TB. Prevalent TB (current antituberculosis treatment or active TB) was present in 25% and was strongly associated with advanced immunodeficiency. During 782 person-years of ART, 81 cases of TB were diagnosed. The incidence was 22.1/100 person-years during the first 3 months of ART and decreased to an average of 4.5/100 person-years during the second and third years. In multivariate analysis, risk of incident TB during follow-up was only associated with the current absolute CD4 cell count at that time point; an increase of 100 cells/mul was associated with a 25% lower risk (P = 0.007). Although prevalent and incident TB were associated with greater than two-fold increased mortality risk, they did not compromise immunological and virological outcomes among survivors at 48 weeks. CONCLUSIONS: Late initiation of ART was associated with a major burden of TB in this ART programme. TB reduced survival but did not impair immunovirological outcomes. Reductions in TB incidence during ART were dependent on CD4 cell count; however, after 3 years of treatment, rates were still 5- to 10-fold higher than among non-HIV-infected people. Earlier initiation of ART may reduce this burden of TB.

Adult↗
PubMed2006

CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa.

BACKGROUND: Patients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency. Previous data suggest that such patients may have diminished capacity for CD4 cell count recovery. METHODS: Rates of CD4 cell increase were determined over 48 weeks among ART-naïve individuals (n = 596) commencing ART in a South African community-based ART programme. RESULTS: The CD4 cell count increased from a median of 97 cells/microl at baseline to 261 cells/microl at 48 weeks and the proportion of patients with a CD4 cell count < 100 cells/microl decreased from 51% at baseline to just 4% at 48 weeks. A rapid first phase of recovery (0-16 weeks, median rate = 25.5 cells/microl/month) was followed by a slower second phase (16-48 weeks, median rate = 7.7 cells/microl/month). Compared to patients with higher baseline counts, multivariate analysis showed that those with baseline CD4 counts < 50 cells/microl had similar rates of phase 1 CD4 cell recovery (P = 0.42), greater rates of phase 2 recovery (P = 0.007) and a lower risk of immunological non-response (P = 0.016). Among those that achieved a CD4 cell count > 500 cells/microl at 48 weeks, 19% had baseline CD4 cell counts < 50 cells/microl. However, the proportion of these patients that attained a CD4 count 200 cells/microl at 48 weeks was lower than those with higher baseline CD4 cell counts. CONCLUSION: Patients in this cohort with baseline CD4 cell counts < 50 cells/microl have equivalent or greater capacity for immunological recovery during 48 weeks of ART compared to those with higher baseline CD4 cell counts. However, their CD4 counts remain < 200 cells/microl for a longer period, potentially increasing their risk of morbidity and mortality in the first year of ART.

Adult↗
PubMed2006

Impact of HIV infection on the epidemiology of tuberculosis in a peri-urban community in South Africa: the need for age-specific interventions.

BACKGROUND: In August 2005, the World Health Organization declared the tuberculosis (TB) epidemic in Africa to be a regional emergency. Current TB-control measures are failing, largely as a result of the human immunodeficiency virus (HIV) epidemic. Evaluation of additional control interventions requires detailed understanding of the epidemiological relationship between these diseases at the community level. METHODS: We examined age- and sex-specific trends in TB notifications and their association with the prevalence of HIV infection in a peri-urban township in South Africa during 1996-2004. Denominators for TB notifications were derived from population census data. The local TB-control program used the World Health Organization directly observed treatment, short-course (DOTS) strategy. RESULTS: TB notification rates increased 2.5-fold during the period, reaching a rate of 1468 cases per 100,000 persons in 2004 (P=.007, by test for trend); the estimated population prevalence of HIV infection increased from 6% to 22% during the same period. After stabilization of prevalence of HIV infection, the TB notification rate continued to increase steeply, indicating ongoing amplification of the TB epidemic. In 2004, at least 50% of children aged 0-9 years who developed TB were HIV infected. Annual TB notification rates among adolescents increased from 0 cases in 1996-1997 to 436 cases per 100,000 persons in 2003-2004, and these increases were predominantly among female. However, 20-39-year-old persons were affected most, with TB notification rates increasing from 706 to 2600 cases per 100,000 persons among subjects in their 30s. In contrast, TB rates among persons aged >50 years did not change. CONCLUSIONS: HIV infection is driving the TB epidemic in this population, and use of the DOTS strategy alone is insufficient. TB notifications have reached unprecedented levels, and additional targeted, age-specific interventions for control of TB and HIV infection in such populations are needed.

Adolescent↗
PubMed2006

Interactions between HIV infection and leprosy: a paradox.

Early in the HIV epidemic it was feared that the disease would undermine leprosy control, as has occurred with tuberculosis. It was predicted that patients with leprosy and HIV coinfection would have an increased risk of lepromatous disease and a faster clinical evolution, and that the leprosy would be more difficult to treat. None of these concerns have materialised and the interaction between HIV and Mycobacterium leprae seems to be far more subtle than that between HIV and tuberculosis. We review the epidemiological, clinical, and pathological data relating to leprosy/HIV coinfection. The published epidemiological data are limited in quality but show neither an increased HIV prevalence among leprosy cases nor an alteration in clinical spectrum of leprosy among coinfected patients. Some data suggest that immune-mediated reactions that complicate leprosy occur at a higher frequency in coinfected patients. Leprosy has now been reported presenting as immune reconstitution disease among patients commencing highly active antiretroviral treatment. Histopathological observations reveal a normal spectrum of appearances in biopsies of leprosy lesions from coinfected patients, even among those with advanced immunodeficiency. These observations suggest that cell-mediated immune responses to M leprae are preserved at the site of disease despite evidence that these responses are abrogated systemically, by contrast with tuberculosis, in which the host granulomatous response is impaired by HIV coinfection. We speculate that this paradox may relate to differences between the activation state and rates of cell turnover within leprosy and tuberculosis granulomas that differentially affect the susceptibility of the granulomas to HIV. The interactions between leprosy and HIV have been little studied and further research on the clinical, pathological, and management aspects of this coinfection is warranted.

Female↗
PubMed2005

Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design.

OBJECTIVES: To determine rates, risk factors and causes of death among patients accessing a community-based antiretroviral treatment (ART) programme both prior to and following initiation of treatment. METHODS: All in-programme deaths were ascertained between September 2002 and March 2005 among treatment-naive patients enrolled into a prospective community-based ART cohort in Cape Town, South Africa. RESULTS: Of 712 patients (median CD4 cell count, 94 cells/microl), 578 (81%) started triple ART a median of 29 days after enrollment. 68 (9.5%) patients died during 563 person-years of observation. The high pretreatment mortality rate of 35.6 deaths/100 person-years [95% confidence interval (CI), 23.0-55.1) decreased to 2.5/100 person-years (95% CI, 0.9-6.6) at 1 year among those who received ART. However, within the first 90 days from enrollment, 29 of 44 (66%) deaths occurred among patients awaiting ART; these would not be identified by an on-treatment analysis. Multivariate analysis showed that risk of death (both pre-treatment and on-treatment) was independently associated with baseline CD4 cell count and World Health Organization (WHO) clinical stage; stage 4 disease was the strongest risk factor. Major attributed causes of death were wasting syndrome, tuberculosis, acute bacterial infections, malignancy and immune reconstitution disease. CONCLUSIONS: Most early in-programme deaths occurred among patients with advanced immunodeficiency but who had not yet started ART. Programme evaluation using on-treatment analyses greatly underestimated early mortality. This mortality would be reduced by minimizing unnecessary in-programme delays in treatment initiation and by starting ART before development of WHO stage 4 disease.

Adolescent↗
PubMed2005

Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort.

OBJECTIVES: To determine the long-term incidence of tuberculosis (TB) and associated risk factors among individuals receiving HAART in South Africa. DESIGN: Prospective cohort study. METHODS: Microbiologically or histologically confirmed incident TB was identified in a hospital-based cohort of 346 patients receiving HAART between 1996 and 2005 in Cape Town. RESULTS: The TB incidence density rate was 3.5/100 person-years in the first year and significantly decreased during follow-up, reaching 1.01/100 person-years in the fifth year (P = 0.002 for trend). TB incidence during the study was highest among patients with baseline CD4 cell counts < 100 cells/microl and those with World Health Organization (WHO) clinical stage 3 or 4 disease (5.71 and 3.88/100 person-years, respectively). Risk of TB was independently associated with CD4 cell count < 100 cells/microl (adjusted risk ratio [ARR], 2.38; 95% confidence interval (CI), 1.01-5.60; P = 0.04), WHO stage 3 or 4 disease (ARR, 3.60; 95% CI, 1.32-9.80; P = 0.01) and age < 33 years (ARR, 2.86; 95% CI, 1.29-6.34; P = 0.01). Risk of TB was not independently associated with plasma viral load, previous history of TB, low socioeconomic status or sex. Despite similar virological responses to HAART, blood CD4 cell count increases were much smaller among patients who developed TB than among those who remained free of TB. CONCLUSIONS: Incidence of TB continues to decrease during the first 5 years of HAART and so HAART may contribute more to TB control in low-income countries than was previously estimated from short-term follow-up. Patients with advanced pretreatment immunodeficiency had persistently increased risk of TB during HAART; this may reflect limited capacity for immune restoration among such patients.

AIDS-Related Opportunistic Infections↗