OpenUCT :: Browsing by Author "Wood, Robin"

Browsing by Author "Wood, Robin"

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Open Access
Acute dichromate poisoning following the use of toxic purgatives
(1990) Wood, Robin
During the last ten years, several patients have presented to the Renal Unit of Groote Schuur Hospital with acute renal failure following the use of traditional (N'anga or Gqirha) medication. The history together with abnormal liver-function tests and renal failure was thought to be suggestive of a toxic aetiology. The specific toxin however remained unknown, until during the admission of one patient, a relative brought in the medication, analysis of which revealed a high concentration of potassium dichromate. Subsequently elevated levels of chromium were demonstrated by atomic absorption spectrometry in the blood and urine of this patient. Following this case there have been six further cases of acute renal failure resulting from use of dichromate containing traditional remedies. These remedies were obtained from a variety of sources including street-hawkers, herbal chemists, and traditional healers. Clinical and laboratory data relating to these seven patients will be presented.
Open Access
Acute dichromate poisoning following the use of toxic purgatives
(1990) Wood, Robin
During the last ten years, several patients have presented to the Renal Unit of Groote Schuur Hospital with acute renal failure following the use of traditional (N'anga or Gqirha) medication. The history together with abnormal liver-function tests and renal failure was thought to be suggestive of a toxic aetiology. The specific toxin however remained unknown, until during the admission of one patient, a relative brought in the medication, analysis of which revealed a high concentration of potassium dichromate. Subsequently elevated levels of chromium were demonstrated by atomic absorption spectrometry in the blood and urine of this patient. Following this case there have been six further cases of acute renal failure resulting from use of dichromate containing traditional remedies. These remedies were obtained from a variety of sources including street-hawkers, herbal chemists, and traditional healers. Clinical and laboratory data relating to these seven patients will be presented.
Open Access
Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa
(Public Library of Science, 2010) Brinkhof, Martin W G; Spycher, Ben D; Yiannoutsos, Constantin; Weigel, Ralf; Wood, Robin; Messou, Eugène; Boulle, Andrew; Egger, Matthias; Sterne, Jonathan A C; (IeDEA), for the International epidemiological Database to Evaluate AIDS
BACKGROUND: Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up. Methods and FINDINGS: Treatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9-6.5%) to 10.9% (9.6-12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9-11.6%) to 16.9% (15.0-19.1%), with relative increases in mortality ranging from 27% to 73% across programmes. CONCLUSIONS: Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.
Open Access
Antiretroviral therapy in a community clinic - early lessons from a pilot project
(Health and Medical Publishing Group, 2003) Bekker, Linda-Gail; Orrell, Catherine; Reader, Larissa; Matoti, Larissa; Cohen, Karen; Martell, Rob; Abdullah, Fareed; Wood, Robin
Objectives. To report on operational and clinical problems encountered during the first 6 months of a community-based antiretroviral therapy (ART) programme. Methods. ART was implemented in a primary care setting utilising an easily replicable service-delivery model based on a medical officer and nurse. Therapeutic counsellors, themselves HIV-infected, provided counselling and adherence support. Drug and monitoring costs were charitably funded and provincial health authorities supplied the medical infrastructure. The HIV Research Unit, University of Cape Town, supplied training and additional clinical support. Local HIV primary care clinics provided patient referrals. Standardised ART regimens were used with strict entry criteria (AIDS or CD4 count < 200 cells/µl). Results. Demand for the service was high. Referred patients had advanced disease (AIDS 57%, median CD4 count 96/µl) and high pre-treatment mortality (83/100 person-years). Mycobacterial disease was a major contributor to this mortality (40%). Scheduled clinic visit hours were six times higher during recruitment than maintenance. Attributable costs were: drugs 61%, staff 27%, viral load and CD4 cell counts 10% and safety monitoring 2%. Viral load after 16 weeks of therapy was < 400 copies/ml in the first 16 patients. Conclusions. ART can be successfully implemented within a primary care setting. Drug purchases and staff salaries drive programme costing. The service model is capable of managing 250 - 300 patients on chronic ART, but staffing needs to be increased during recruitment. Attention must be given to the diagnosis of tuberculosis during screening and early ART. Incorporating therapeutic counsellors into the programme increased community involvement and utilised a valuable and previously untapped resource.
Open Access
Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods
(Public Library of Science, 2011) Kranzer, Katharina; Lewis, James J; White, Richard G; Glynn, Judith R; Lawn, Stephen D; Middelkoop, Keren; Bekker, Linda-Gail; Wood, Robin
BACKGROUND: Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported. METHODS: This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods. RESULTS: The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data. CONCLUSION: The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.
Open Access
Are the effects of isoniaid preventive therapy and highly active antiretroviral therapy additive in preventing HIV-associated tuberculosis
(2009) Wood, Robin; Lawn, Stephen D; Bekker, Linda-Gail
Golub et al. [1] recently reported a retrospective analysis of rates of incident tuberculosis (TB) in a large observational cohort of 2778 patients accessing HIV care in rural and urban South Africa. The TB incidence rate was highest [7.1/100 person-years; 95% confidence interval (CI)¼ 6.2–8.2] during the period of care when patients did not receive isoniazid preventive therapy (IPT) or highly active antiretroviral therapy (HAART). The rates were lower during person-time that accrued throughout follow-up after initiation of IPT (5.2/100 person-years; 95% CI¼ 3.4–7.8) and throughout follow-up on HAART alone (4.6/100 person-years, 95% CI¼ 3.4– 6.2). The rate was lower still (1.1/100 person-years 95% CI¼ 0.2–7.6) during person-time accrued during sequential IPT and HAART (IPTþ HAART). The authors concluded that TB risk was significantly reduced by IPT in HAART-treated adults. It was further concluded that 'the dramatic reduction in TB risk' demonstrated in this study together with supportive data from a similarly analysed study from Brazil [2] indicates that widespread use 1444 AIDS 2009, Vol 23 No 11 Fig. 1. T2-weighted flair image demonstrating enhancing lesion in the right precentral gyrus. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. of IPT should be implemented in conjunction with the roll-out of HAART.
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Are the effects of isoniaid preventive therapy and highly active antiretroviral therapy additive in preventing HIV-associated tuberculosis
(2009) Wood, Robin; Lawn, Stephen D; Bekker, Linda-Gail
Golub et al. [1] recently reported a retrospective analysis of rates of incident tuberculosis (TB) in a large observational cohort of 2778 patients accessing HIV care in rural and urban South Africa. The TB incidence rate was highest [7.1/100 person-years; 95% confidence interval (CI)¼ 6.2–8.2] during the period of care when patients did not receive isoniazid preventive therapy (IPT) or highly active antiretroviral therapy (HAART). The rates were lower during person-time that accrued throughout follow-up after initiation of IPT (5.2/100 person-years; 95% CI¼ 3.4–7.8) and throughout follow-up on HAART alone (4.6/100 person-years, 95% CI¼ 3.4– 6.2). The rate was lower still (1.1/100 person-years 95% CI¼ 0.2–7.6) during person-time accrued during sequential IPT and HAART (IPTþ HAART). The authors concluded that TB risk was significantly reduced by IPT in HAART-treated adults. It was further concluded that ‘the dramatic reduction in TB risk’ demonstrated in this study together with supportive data from a similarly analysed study from Brazil [2] indicates that widespread use 1444 AIDS 2009, Vol 23 No 11 Fig. 1. T2-weighted flair image demonstrating enhancing lesion in the right precentral gyrus. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. of IPT should be implemented in conjunction with the roll-out of HAART.
Open Access
Asking the right questions: developing evidence-based strategies for treating HIV in women and children
(BioMed Central Ltd, 2011) Karim, Quarraisha; Banegura, Anchilla; Cahn, Pedro; Christie, Celia; Dintruff, Robert; Distel, Manuel; Hankins, Catherine; Hellmann, Nicholas; Katabira, Elly; Lehrman, Sandra; Montaner, Julio; Purdon, Scott; Rooney, James; Wood, Robin; Heidari, Shiri
In July 2010, the World Health Organization (WHO) issued formal revisions of its guidelines on the use of highly active antiretroviral therapy for HIV. The new guidelines greatly expand eligibility for treatment of adults and children, as well as for pregnant women seeking prophylaxis for vertical HIV transmission. WHO's new recommendations bring the guidelines closer to practices in developed countries, and its shift to earlier treatment alone will increase the number of treatment-eligible people by 50% or more.Scaling up access to HIV treatment is revealing important gaps in our understanding of how best to provide for all those in need. This knowledge gap is especially significant in developing countries, where women and children comprise a majority of those living with HIV infection. Given the magnitude and significance of these populations, the International AIDS Society, through its Industry Liaison Forum, prioritized HIV treatment and prophylaxis of women and children. In March 2010, the International AIDS Society and 15 partners launched a Consensus Statement outlining priority areas in which a relative lack of knowledge impedes delivery of optimal prevention of mother to child transmission (PMTCT) and treatment to women and children.The Consensus Statement, "Asking the Right Questions: Advancing an HIV Research Agenda for Women and Children", makes a special appeal for a more gender-sensitive approach to HIV research at all stages, from conception to design and implementation. It particularly emphasizes research to enhance the understanding of sex-based differences and paediatric needs in treatment uptake and response. In addition to clinical issues, the statement focuses on programmatic research that facilitates access and adherence to antiretroviral regimens. Better coordination of HIV management with sexual and reproductive healthcare delivery is one such approach.We discuss here our knowledge gaps concerning effective, safe PMTCT and treatment for women and children in light of the expansion envisioned by WHO's revised guidelines. The guideline's new goals present an opportunity for advancing the women and children's agenda outlined in the Consensus Statement.
Open Access
Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis: association with sputum mycobacterial load
(Public Library of Science, 2013) Kerkhoff, Andrew D; Wood, Robin; Lowe, David M; Vogt, Monica; Lawn, Stephen D
BACKGROUND: Increasing evidence suggests that neutrophils play a role in the host response to Mycobacterium tuberculosis . We determined whether neutrophil counts in peripheral blood are associated with tuberculosis (TB) and with mycobacterial load in sputum in HIV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Adults enrolling in an antiretroviral treatment (ART) clinic in a Cape Town township were screened for TB regardless of symptoms. Paired sputum samples were examined using liquid culture, fluorescence microscopy, and the Xpert MTB/RIF assay. Absolute neutrophil counts (ANC) were measured in blood samples. Of 602 HIV-infected patients screened, 523 produced one or more sputum samples and had complete results available for analysis. Among these 523 patients, the median CD4 count was 169×10 9 /L (IQR, 96-232) and median ANC was 2.6×10 9 /L (IQR, 1.9-3.6). Culture-positive pulmonary tuberculosis was diagnosed in 89 patients. Patients with TB had a median ANC of 3.4×10 9 /L (IQR, 2.4-5.1) compared to 2.5×10 9 /L (IQR, 1.8-3.4) among those who were culture negative (p<0.0001). In multivariable analyses, having pulmonary TB was associated with an adjusted risk ratio (aRR) of 2.6 (95%CI, 1.5-4.5) for having an ANC level that exceeded the median value (ANC ≥2.6×10 9 /L; p = 0.0006) and an aRR of 6.8 (95%CI, 2.3-20.4) for having neutrophilia defined by a neutrophil count exceeding the upper limit of the normal range (ANC >7.5×10 9 /L; p = 0.0005). Patients were then classified into four mutually exclusive groups with increasing sputum mycobacterial load as defined by the results of culture, Xpert MTB/RIF and sputum smear microscopy. Multivariable analyses demonstrated that increasing sputum mycobacterial load was positively associated with blood ANC ≥2.6×10 9 /L and with neutrophilia. Conclusions/Significance Increased blood neutrophil counts were independently associated with pulmonary TB and sputum mycobacterial burden in this HIV-infected patient group. This observation supports the growing body of literature regarding the potential role for neutrophils in the host response to TB.
Open Access
Burden of new and recurrent tuberculosis in a major South African city stratified by age and HIV-status
(Public Library of Science, 2011) Wood, Robin; Lawn, Stephen D; Caldwell, Judy; Kaplan, Richard; Middelkoop, Keren; Bekker, Linda-Gail
Aim: To describe the burden of tuberculosis (TB) in Cape Town by calculating TB incidence rates stratified by age and HIV-status, assessing the contribution of retreatment disease and estimating the cumulative lifetime TB risk in HIV-negative individuals. METHODS: Details of TB cases were abstracted from the 2009 electronic TB register. Population denominators were estimated from census data and actuarial estimates of HIV prevalence, allowing calculation of age-specific and HIV-stratified TB notification rates. RESULTS: The 2009 mid-year population was 3,443,010 (3,241,508 HIV-negative and 201,502 HIV-positive individuals). There were 29,478 newly notified TB cases of which 56% were laboratory confirmed. HIV status was recorded for 87% of cases and of those with known HIV-status 49% were HIV-negative and 51% were positive. Discrete peaks in the incidence of non-HIV-associated TB occurred at three ages: 511/100,000 at 0-4 years of age, 553/100,000 at 20-24 years and 628/100,000 at 45-49 years with 1.5%, 19% and 45% being due to retreatment TB, respectively. Only 15.5% of recurrent cases had a history of TB treatment failure or default. The cumulative lifetime risks in the HIV-negative population of all new TB episodes and new smear-positive TB episodes were 24% and 12%, respectively; the lifetime risk of retreatment disease was 9%. The HIV-positive notification rate was 6,567/100,000 (HIV-associated TB rate ratio = 17). Although retreatment cases comprised 30% of the HIV-associated TB burden, 88% of these patients had no history of prior treatment failure or default. CONCLUSIONS: The annual burden of TB in this city is huge. TB in the HIV-negative population contributed almost half of the overall disease burden and cumulative lifetime risks were similar to those reported in the pre-chemotherapy era. Retreatment TB contributed significantly to both HIV-associated and non-HIV-associated TB but infrequently followed prior inadequate treatment. This likely reflects ongoing TB transmission to both HIV-negative and positive individuals.
Open Access
CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa
(BioMed Central Ltd, 2006) Lawn, Stephen; Myer, Landon; Bekker, Linda-Gail; Wood, Robin
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-naive 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/mul at baseline to 261 cells/mul at 48 weeks and the proportion of patients with a CD4 cell count <100 cells/mul 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/mul/month) was followed by a slower second phase (16-48 weeks, median rate = 7.7 cells/mul/month). Compared to patients with higher baseline counts, multivariate analysis showed that those with baseline CD4 counts <50 cells/mul 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/mul at 48 weeks, 19% had baseline CD4 cell counts <50 cells/mul. However, the proportion of these patients that attained a CD4 count 200 cells/mul 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/mul 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/mul for a longer period, potentially increasing their risk of morbidity and mortality in the first year of ART.
Open Access
A century of tuberculosis epidemiology in the northern and southern hemisphere: the differential impact of control interventions
(Public Library of Science, 2015) Hermans, Sabine; Jr, C Robert Horsburgh; Wood, Robin
BACKGROUND: Cape Town has one of the highest TB burdens of any city in the world. In 1900 the City of Cape Town, New York City and London had high mortality of tuberculosis (TB). Throughout the 20th century contemporaneous public health measures including screening, diagnosis and treatment were implemented in all three settings. Mandatory notification of TB and vital status enabled comparison of disease burden trajectories. METHODS: TB mortality, notification and case fatality rates were calculated from 1912 to 2012 using annual TB notifications, TB death certifications and population estimates. Notification rates were stratified by age and in Cape Town by HIV status (from 2009 onwards). RESULTS: Pre-chemotherapy, TB mortality and notification rates declined steadily in New York and London but remained high in Cape Town. Following introduction of combination chemotherapy, mean annual case fatality dropped from 45-60% to below 10% in all three settings. Mortality and notification rates subsequently declined, although Cape Town notifications did not decline as far as those in New York or London and returned to pre-chemotherapy levels by 1980. The proportional contribution of childhood TB diminished in New York and London but remained high in Cape Town. The advent of the Cape Town HIV-epidemic in the 1990s was associated with a further two-fold increase in incidence. In 2012, notification rates among HIV-negatives remained at pre-chemotherapy levels. CONCLUSIONS: TB control was achieved in New York and London but failed in Cape Town. The TB disease burden trajectories started diverging before the availability of combination chemotherapy in 1952 and further diverged following the HIV epidemic in 1990. Chemotherapy impacted case fatality but not transmission, evidenced by on-going high childhood TB rates. Currently endemic TB results from high on-going transmission, which has been exacerbated by the HIV epidemic. TB control will require reducing transmission, which is inexorably linked to prevailing socio-economic factors.
Open Access
Childhood tuberculosis infection and disease: A spatial and temporal transmission analysis in a South African township
(2009) Middelkoop, Keren; Bekker, Linda-Gail; Morrow, Carl; Zwane, Eugene; Wood, Robin
Background. Tuberculosis (TB) remains a leading cause of South African mortality and morbidity. While adult TB arises from both recent and prior infection, childhood TB results from recent infection and reflects ongoing transmission occurring despite current TB control strategies. Setting. A South African community with high rates of TB and HIV disease. Outcomes. A Geographic Information System was used to spatially and temporally define the relationships between TB exposure, infection and disease in children <15 years of age, with exposure to adult HIV-positive and HIV-negative TB disease on residential plots between 1997 and 2007. Results. During the study period the annual adult TB notification rate increased from 629 to 2106/100,000 and <15yrs TB notification rate ranged between 664/100,000 and 1044/100,000. The mean exposure to adult TB for uninfected children, TB-infected, TB cases was 5.1%, 5.4% and 33% per annum and the mean number of adult smear-positive cases per exposed child was 1.0, 1.6 and 1.9 respectively. Acquisition of TB infection was not associated with HIV status of adult exposure TB case and 36% of child TB cases were diagnosed prior to the temporally closest adult case on their plot. Conclusions. Childhood infection and disease were quantitatively linked to infectious adult TB prevalence in an immediate social network. Childhood infection should be monitored in high burden settings as a marker of ongoing TB transmission. Improved knowledge of township childhood and adult social networks may also facilitate targeted active case finding, which may provide an adjunct to presently failing TB control strategies.
Open Access
The clinical and economic impact of point-of-care CD4 testing in Mozambique and other resource-limited settings: a cost-effectiveness analysis
(Public Library of Science, 2014) Hyle, Emily P; Jani, Ilesh V; Lehe, Jonathan; Su, Amanda E; Wood, Robin; Quevedo, Jorge; Losina, Elena; Bassett, Ingrid V; Pei, Pamela P; Paltiel, A David
Emily Hyle and colleagues conduct a cost-effectiveness analysis to estimate the clinical and economic impact of point-of-care CD4 testing compared to laboratory-based tests in Mozambique. Please see later in the article for the Editors' Summary
Open Access
A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment
(Journal of the International AIDS Society, 2015-12-16) Johnson, Leigh F; Dorrington, Rob E; Laubscher, Ria; Hoffmann, Christopher J; Wood, Robin; Fox, Matthew P; Cornell, Morna; Schomaker, Michael; Prozesky, Hans; Tanser, Frank; Davies, Mary-Ann; Boulle, Andrew
Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil ID numbers, and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91 548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa’s civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously-documented improvements in ART mortality over time may be biased if based only on data from patient records.
Open Access
Comparison of six methods to estimate adherence in an ART-naïve cohort in a resource-poor setting: which best predicts virological and resistance outcomes?
(BioMed Central, 2017-04-04) Orrell, Catherine; Cohen, Karen; Leisegang, Rory; Bangsberg, David R; Wood, Robin; Maartens, Gary
Background: Incomplete adherence to antiretroviral therapy (ART) results in virologic failure and resistance. It remains unclear which adherence measure best predicts these outcomes. We compared six patient-reported and objective adherence measures in one ART-naïve cohort in South Africa. Methods: We recruited 230 participants from a community ART clinic and prospectively collected demographic data, CD4 count and HIV-RNA at weeks 0, 16 and 48. We quantified adherence using 3-day self-report (SR), clinicbased pill count (CPC), average adherence by pharmacy refill (PR-average), calculation of medication-free days (PR-gaps), efavirenz therapeutic drug monitoring (TDM) and an electronic adherence monitoring device (EAMD). Associations between adherence measures and virologic and genotypic outcomes were modelled using logistic regression, with the area under the curve (AUC) from the receiver operator characteristic (ROC) analyses derived to assess performance of adherence measures in predicting outcomes. Results: At week 48 median (IQR) adherence was: SR 100% (100–100), CPC 100% (95–107), PR-average 103% (95– 105), PR-gaps 100% (95–100) and EAMD 86% (59–94), and efavirenz concentrations were therapeutic (>1 mg/L) in 92%. EAMD, PR-average, PR-gaps and CPC best predicted virological outcome at week 48 with AUC ROC of 0.73 (95% CI 0.61–0.83), 0.73 (95% CI 0.61–0.85), 0.72 (95% CI 0.59–0.84) and 0.64 (95% CI 0.52–0.76) respectively. EAMD, PR-gaps and PR-average were highly predictive of detection of resistance mutations at week 48, with AUC ROC of 0.92 (95% CI 0.87–0.97), 0.86 (0.67–1.0) and 0.83 (95% CI 0.65–1.0) respectively. SR and TDM were poorly predictive of outcomes at week 48. Conclusion: EAMD and both PR measures predicted resistance and virological failure similarly. Pharmacy refill data is a pragmatic adherence measure in resource-limited settings where electronic monitoring is unavailable. Trial registration The trial was retrospectively registered in the Pan African Clinical Trials Registry, number PACTR201311000641402, on the 13 Sep 2013 (www.pactr.org). The first participant was enrolled on the 12th July 2012. The last patient last visit (week 48) was 15 April 2014
Open Access
Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study
(Public Library of Science, 2013) Pathai, Sophia; Lawn, Stephen D; Shiels, Paul G; Weiss, Helen A; Cook, Colin; Wood, Robin; Gilbert, Clare E
BACKGROUND: Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults. METHODS: Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma. RESULTS: The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00-2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12-6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD. CONCLUSIONS: The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.
Open Access
Correcting mortality for loss to follow-up: a nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa
(Public Library of Science, 2011) Egger, Matthias; Spycher, Ben D; Sidle, John; Weigel, Ralf; Geng, Elvin H; Fox, Matthew P; MacPhail, Patrick; van Cutsem, Gilles; Messou, Eugène; Wood, Robin
Background: The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART. Methods and Findings: We developed a nomogram to correct mortality estimates for loss to follow-up, based on the fact that mortality of all patients starting ART in a treatment programme is a weighted average of mortality among patients lost to follow-up and patients remaining in care. The nomogram gives a correction factor based on the percentage of patients lost to follow-up at a given point in time, and the estimated ratio of mortality between patients lost and not lost to follow-up. The mortality observed among patients retained in care is then multiplied by the correction factor to obtain an estimate of programme-level mortality that takes all deaths into account. A web calculator directly calculates the corrected, programme-level mortality with 95% confidence intervals (CIs). We applied the method to 11 ART programmes in sub-Saharan Africa. Patients retained in care had a mortality at 1 year of 1.4% to 12.0%; loss to follow-up ranged from 2.8% to 28.7%; and the correction factor from 1.2 to 8.0. The absolute difference between uncorrected and corrected mortality at 1 year ranged from 1.6% to 9.8%, and was above 5% in four programmes. The largest difference in mortality was in a programme with 28.7% of patients lost to follow-up at 1 year. Conclusions: The amount of bias in mortality estimates can be large in ART programmes with substantial loss to follow-up. Programmes should routinely report mortality among patients retained in care and the proportion of patients lost. A simple nomogram can then be used to estimate mortality among all patients who started ART, for a range of plausible mortality rates among patients lost to follow-up.
Open Access
Correction to: Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol
(2020-08-24) Patterson, Benjamin; Koch, Anastasia; Gessner, Sophia; Dinkele, Ryan; Gqada, Melitta; Bryden, Wayne; Cobelens, Frank; Little, Francesca; Warner, Digby F; Wood, Robin
An amendment to this paper has been published and can be accessed via the original article
Open Access
Cost effectiveness of cryptococcal antigen screening as a strategy to prevent HIV-associated cryptococcal meningitis in South Africa
(Public Library of Science, 2013) Jarvis, Joseph N; Harrison, Thomas S; Lawn, Stephen D; Meintjes, Graeme; Wood, Robin; Cleary, Susan
Objectives Cryptococcal meningitis (CM)-related mortality may be prevented by screening patients for sub-clinical cryptococcal antigenaemia (CRAG) at antiretroviral-therapy (ART) initiation and pre-emptively treating those testing positive. Prior to programmatic implementation in South Africa we performed a cost-effectiveness analysis of alternative preventive strategies for CM. Design Cost-effectiveness analysis. METHODS: Using South African data we modelled the cost-effectiveness of four strategies for patients with CD4 cell-counts <100 cells/µl starting ART 1) no screening or prophylaxis (standard of care), 2) universal primary fluconazole prophylaxis, 3) CRAG screening with fluconazole treatment if antigen-positive, 4) CRAG screening with lumbar puncture if antigen-positive and either amphotericin-B for those with CNS disease or fluconazole for those without. Analysis was limited to the first year of ART. RESULTS: The least costly strategy was CRAG screening followed by high-dose fluconazole treatment of all CRAG-positive individuals. This strategy dominated the standard of care at CRAG prevalence ≥0.6%. Although CRAG screening followed by lumbar puncture in all antigen-positive individuals was the most effective strategy clinically, the incremental benefit of LPs and amphotericin therapy for those with CNS disease was small and additional costs were large (US$158 versus US$51per person year; incremental cost effectiveness ratio(ICER) US$889,267 per life year gained). Both CRAG screening strategies are less costly and more clinically effective than current practice. Primary prophylaxis is more effective than current practice, but relatively cost-ineffective (ICER US$20,495). CONCLUSIONS: CRAG screening would be a cost-effective strategy to prevent CM-related mortality among patients initiating ART in South Africa. These findings provide further justification for programmatic implementation of CRAG screening.