Robin Wood | University of Cape Town (original) (raw)

Papers by Robin Wood

Southern African Journal of HIV Medicine, 2016

In response to this challenge, the HIV Resistance Response Database Initiative (RDI) has develope... more In response to this challenge, the HIV Resistance Response Database Initiative (RDI) has developed computational models to assist in the selection of the most effective combinations of drugs from those available. 5,6 The models are able to predict accurately virological response to combination antiretroviral therapy, with or without genotypic information, the latter basing their predictions on viral loads, CD4 counts, treatment history and time to follow-up. 7,8 The RDI models are trained using longitudinal data from clinical cases where the HIV treatment has been changed and followed up. A case with all the necessary data (e.g. viral load and Background: Selecting the optimal combination of HIV drugs for an individual in resourcelimited settings is challenging because of the limited availability of drugs and genotyping. Objective: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, using cases from the Phidisa cohort in South Africa. Methods: Cases from Phidisa of treatment change following failure were identified that had the following data available: baseline CD4 count and viral load, details of failing and previous antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV Resistance Response Database Initiative's (RDI's) models used these data to predict the probability of a viral load < 50 copies/mL at follow-up. The models were also used to identify effective alternative combinations of three locally available drugs. Results: The models achieved accuracy (area under the receiver-operator characteristic curve) of 0.72 when predicting response to therapy, which is less accurate than for an independent global test set (0.80) but at least comparable to that of genotyping with rules-based interpretation. The models were able to identify alternative locally available three-drug regimens that were predicted to be effective in 69% of all cases and 62% of those whose new treatment failed in the clinic. Conclusion: The predictive accuracy of the models for these South African patients together with the results of previous studies suggest that the RDI's models have the potential to optimise treatment selection and reduce virological failure in different patient populations, without the use of a genotype.

Journal of Infectious Diseases, 1994

The safety, immunologic, and antiviral effects of a recombinant biologic product that combines th... more The safety, immunologic, and antiviral effects of a recombinant biologic product that combines the second and third domains of the CD4 molecule and Pseudomonas exotoxin A (PE40) were evaluated in 21 human immunodeficiency virus (HIV)-infected subjects in a phase III open-label dose-ranging study. Subjects with CD4+ lymphocyte counts of 100-500/mm3 received CD4-PE40 at 40, 80, or 160 micrograms/m2 by infusion three to seven times over 10 days. At the maximum tolerated dose (80 micrograms/m2), peak CD4-PE40 levels were 65-130 ng/mL with a serum half-life of 3.6 +/- 1.5 h. Toxicity, primarily increased hepatic transaminases, was dose-related and reversible. HIV DNA proviral levels in peripheral blood mononuclear cells and plasma HIV RNA remained stable during and after CD4-PE40 infusions. The relative resistance of clinical isolates of HIV, limits of the tolerated dose, and the immunogenicity and short half-life of the protein may explain the lack of in vivo antiviral effect of CD4-PE40.

The Journal of Infectious Diseases, 2017

Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in... more Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed.

Mycobacterial Diseases, 2016

Much of our current knowledge of Mycobacterium tuberculosis (MTB) transmission originates from se... more Much of our current knowledge of Mycobacterium tuberculosis (MTB) transmission originates from seminal human-to-guinea pig in vivo studies, carried out in the 1950s. Similar methodology has been used to investigate human immunodeficiency virus (HIV) co-infection and multidrug resistant TB. However, all these studies have had to reconcile the need to use high facility ventilation rates in order to decrease risks of human-to-human infection while demonstrating human-to-guinea pig transmission. While these studies demonstrate tuberculosis (TB) contagion can be airborne they also estimated extremely low infectivity of TB cases. However, calculated infectivity was based on a theoretical concept of quantal infection and assumed that the guinea pig model was 100% sensitivity for the remote detection of viable TB organisms in highly diluted air exhausted from the facility. High facility ventilation markedly decreases the probability of a successful guinea pig infection by both dilution of the exhaled breath and decreasing the proportion of air sampled by guinea pigs. In this study, we used a new mathematical model based on Poisson distribution and previous guinea pig experimental data to quantify a more realistic estimate of the number of infective organisms required to produce a successful infection for exposed guinea pigs in the in vivo studies. Furthermore, we explored the probability of exposed guinea pigs acquiring infection in these studies. We found that the in vivo studies to date were underestimated to demonstrate transmission derived from any but the most productive infectious cases. All four in vivo studies have remarkably low probability of infection of exposed guinea pigs due to either high ventilation rates or insensitive mathematical model used in these studies. Therefore, our analysis would suggest that the production of infective organisms by TB cases might have been markedly underestimated. This reassessment of the infectivity of guinea pigs is compatible with recent findings of very high numbers of TB genomes present in health care environments and the very diverse distribution of TB strains present in highly endemic settings which indicates a multiplicity of infective sources.

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde

Despite rapid expansion of antiretroviral therapy (ART) in sub-Saharan Africa there are few longi... more Despite rapid expansion of antiretroviral therapy (ART) in sub-Saharan Africa there are few longitudinal data describing programme performance during rapid scale-up. We compared mortality, viral suppression and programme retention in 3 consecutive years of a public sector community-based ART clinic in a South African township. Data were collected prospectively from establishment of services in October 2002 to the censoring date in September 2005. Viral load and CD4 counts were monitored at 4-monthly intervals. Community-based counsellors provided adherence and programme support. During the study period 1139 ART-naïve patients received ART (161, 280 and 698 in the 1st, 2nd and 3rd years respectively). The median CD4 cell counts were 84 cells/microl (interquartile range (IQR) 42-139), 89 cells/microl (IQR 490-149), and 110 cells/microl (IQR 55-172), and the proportions of patients with World Health Organization (WHO) clinical stages 3 and 4 were 90%, 79% and 76% in each sequential yea...

Antiviral Therapy

Background This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in th... more Background This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa. Methods This was an observational cohort. Genotypic resistance testing was performed on treatment-naive individuals and those failing first-line ART (confirmed HIV-1 RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002–2007). Resistance profiles and mutations relative to timing of known virological failure were examined. Results In total, 230 patients (120 treatment-naive and 110 with virological failure) were included: 98% had clade C virus. Among treatment-naive patients, prevalence of primary resistance was 2.5% (95% confidence interval 0.0–5.3). Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A. Among treatment-experienced patients, 95 (86%) individuals had therapy-limiting NNRTI mutations, including ...

Open Forum Infectious Diseases, 2017

BackgroundReports of a single case of human immunodeficiency virus (HIV) eradication suggest that... more BackgroundReports of a single case of human immunodeficiency virus (HIV) eradication suggest that elimination of HIV from individuals is possible. Anticipating both increased research funding and the development of effective, durable cure technologies, we describe the circumstances under which a cure might improve survival and be cost-effective in South Africa.MethodsWe adapted a simulation model comparing a hypothetical cure strategy (“Cure”) to the standard of care, lifetime antiretroviral therapy (“LifetimeART”) among adherent South Africans (58% female; mean age 33.8 years; mean CD4 257/µL; virologic suppression ≥1 year). We portrayed cure as a single intervention, producing sustained viral eradication without ART. We considered both a plausible, more imminently achievable “Baseline Scenario” and a more aspirational “Optimistic Scenario”. Inputs (Baseline/Optimistic) included the following: 50%/75% efficacy; 0.6%/0.0% fatal toxicity; 0.37%/0.085% monthly relapse over 5 years (0....

The International Journal of Tuberculosis and Lung Disease, Apr 1, 2010

Background: With increased enrollment and time spent on ART in resource-limited settings, more AR... more Background: With increased enrollment and time spent on ART in resource-limited settings, more ART-recipients may face virologic failure on 1st-line and require 2nd-line regimens. However, there are few reports on 2nd-line ART effectiveness and factors related to virologic suppression in community-based settings in South Africa. Methods: We analyzed data on patients switched to 2nd-line ART consisting of AZT, ddi, and LPV/r (national treatment guidelines) in a community-based ART program in a Cape Town township. We focused on 24-week virologic suppression (HIV RNA <400 copies/ml) on 2nd-line. We conducted both an “intent to treat (ITT)” analysis, assuming that those with missing data were not suppressed, and an “as-treated” analysis where we excluded missing data. We examined whether early (≤ 90 days) or late (> 90 days) switching after virologic failure (2 consecutive HIV RNA >1000 copies/ml) affected 24-week virologic suppression on 2nd-line ART. Results: Of 2,603 patient...

Journal of the Indian Medical Association, 2009

Infection with human immunodeficiency virus (HIV) is found to increase the occurrence of drug res... more Infection with human immunodeficiency virus (HIV) is found to increase the occurrence of drug resistant tuberculosis. The data for HIV and multidrug resistant tuberculosis (MDR-TB) coinfection is scarce in India. The study aims to find out the prevalence of MDR-TB and extensively drug resistant tuberculosis (XDR-TB) among chronic TB patients and to identify their trend with HIV coinfection over time. Non-responding chronic pulmonary tuberculosis patients were selected for the study from 2004 to 2007. They were all subjected to HIV screening and drug susceptibility testing (DST) for anti-TB drugs. In all 2927 chronic tuberculosis patients were assessed for DST and HIV coinfection; 2156 patients (73.7%) had culturable Mycobacterium tuberculosis in their sputum specimens; 1651 patients (56.4%) were found to have drug resistant mutants to one or more anti-TB drugs; 993 patients (33.9%) had MDR-TB and 48 (1.6%) had XDR-TB. Significantly, 17.9% of 1651 patients with drug resistance were f...

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2014

Objective: To identify determinants of tuberculosis (TB) case fatality including the impact of an... more Objective: To identify determinants of tuberculosis (TB) case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. Methods: Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients aged $15 years. Multivariable Cox proportional hazard models were used to determine the risk factors for TB case fatality in these patients.

The Lancet Infectious Diseases, 2007

Journal of the International AIDS Society, 2008

Journal of the International AIDS Society, 2012

Antiviral Therapy, 2011

Background More patients in resource-limited settings are starting second-line antiretroviral tre... more Background More patients in resource-limited settings are starting second-line antiretroviral treatment (ART) following first-line ART failure. We aimed to describe predictors of lack of virological suppression in HIV-infected patients on second-line ART in a roll-out programme in South Africa. Methods A retrospective analysis was performed on an adult HIV treatment cohort who started second-line ART (lopinavir/ritonavir, didanosine and zidovudine) after virological failure of first-line ART (two consecutive HIV RNA>1,000 copies/ml). Predictors of week 24 lack of suppression (HIV RNA>400 copies/ml) on second-line ART were determined by bivariate analysis where missing equals failure. A multivariable model that adjusted for gender, age and time to ART switch was used. We tested these findings in sensitivity analyses defining lack of suppression at week 24 as HIV RNA>1,000 and >5,000 copies/ml. Results Of 6,339 patients on ART, 202 started second-line ART. At week 24, an e...

levels of soluble urokinase-type plasminogen activator receptor (su-PAR) and early mortality risk... more levels of soluble urokinase-type plasminogen activator receptor (su-PAR) and early mortality risk among patients enrolling for antiretro-viral treatment in South Africa. Bmc Infectious Diseases, 7. ISSN

Clinical Infectious Diseases, 2009

Short-term clinical disease progression in HIV-infected patients receiving combination antiretrov... more Short-term clinical disease progression in HIV-infected patients receiving combination antiretroviral therapy: results from the TREAT Asia HIV Observational Database. Clin Infect Dis 2009; 48: 940-50. 3. The Antiretroviral Therapy in Lower Income Countries Collaboration Group. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between lowincome and high-income countries. Lancet 2006; 367:817-24. 4. World Health Organization (WHO). Global tuberculosis control-epidemiology, strategy, financing. WHO report 2009.

The tuberculosis (TB) pandemic demands urgent interventions such as those designed to interrupt M... more The tuberculosis (TB) pandemic demands urgent interventions such as those designed to interrupt Mycobacterium tuberculosis (Mtb) transmission, a challenge exacerbated by our poor understanding of the events enabling successful transfer of infectious bacilli between hosts. To address this problem, we developed the Respiratory Aerosol Sampling Chamber (RASC), a personal clean-room equipped with high-efficiency filtration and sampling technologies that allow biosafe capture and isolation of particulate matter – including Mtb bacilli – released by patients during natural breathing and (non-induced) cough. Here, we demonstrate the use of DMN-trehalose labelling to detect and quantify live Mtb bacilli among complex bioaerosol samples arrayed in a bespoke nanowell device following capture in the RASC. A pilot study identified Mtb in more than 85 % of known TB patients, improving significantly on previous work which has relied on animal infection and cough sampling to estimate transmission ...