OpenUCT :: Browsing by Author "Johnson, Leigh F"

Browsing by Author "Johnson, Leigh F"

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Open Access
A multi-state model of treatment states in an antiretroviral treatment programme cohort in Cape Town
(2022) Moolla, Haroon; Johnson, Leigh F
Introduction A recent systematic review estimated that almost a quarter of patients in low- and middle-income countries are not retained on antiretroviral treatment (ART) beyond one year. Further, it is difficult to determine whether a patient who is not retained in care has interrupted their treatment, transferred to another treatment facility, or died. Previous studies have been deterministic in classifying loss to follow-up and treatment interruption. This study investigates treatment interruption and resumption rates when accounting for uncertainty in the occurrence of interruptions. The primary objective is to estimate the rate at which ART is interrupted and the rate at which ART is resumed after an interruption. Methods We fitted a multi-state model to data from the Khayelitsha cohort of the International Epidemiologic Databases to Evaluate AIDS. Between 2001 and 2012, 6796 adult patients starting ART were included. Potential treatment interruption periods were defined between contact points 3 or more months apart. To aid the model in determining if a patient truly interrupted treatment a CD4 count model was used. CD4 counts were modelled to drop to baseline by 3 months after the start of a treatment interruption. Bayesian estimation and Markov chain Monte Carlo were used to obtain posterior distributions of parameters. Several scenarios were used in sensitivity testing, including varying the threshold used to define potential treatment interruption periods, and either adjusting or excluding the data of those with CD4 counts that drop below baseline. Results The baseline annual rate of treatment interruption had a posterior mean of 0.060 (95% CI 0.038- 0.087) which is significantly lower than the prior distribution that had a mean of 0.145 (95% CI 0.080-0.229). The posterior distribution of the baseline annual rate of treatment resumption (mean 1.09; 95% CI 0.68-1.65) was consistent with the prior distribution (mean 1.46; 95% CI 0.21-3.90). The posterior distributions of the parameters related to treatment interruption and resumption did not change significantly in sensitivity testing. Conclusion This study indicates that treatment interruption rates may be significantly lower than previously estimated. The methodology of this study may be useful to those measuring retention within ART programmes. An important limitation was that the CD4 count model did not allow for CD4 counts to fall below baseline during periods of treatment interruption. This limits the generalisability of the posterior estimates of the parameters of the CD4 count model. Further research may require a more flexible CD4 count model.
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
Epidemiologic synergy - the contribution of heterosexual HIV transmission to the spread of HIV among men who have sex with men (MSM) in South Africa
(2016) Mulongeni, Pancho; Johnson, Leigh F
Background: Could heterosexual HIV transmission be a driver of HIV infections that occur in men who have sex with men (MSM)? Noting the disproportionately high HIV prevalence among MSM across a variety of settings, this subpopulation is often considered as sources of new infections, overlooking the possibility of HIV transmission from the heterosexual – general – population to MSM. Objective: To assess the relative contribution of heterosexual transmission of HIV for onwards transmission of HIV from one man to another. Method: An agent based model of heterosexual transmission of HIV in South Africa was extended to simulate the HIV epidemic among MSM from 1990 to 2012. The model included gay men (who only have sex with men), bisexual men (who have partners of both sexes) in addition to men who have sex with women. HIV prevalence and sexual behaviour data collected among MSM in South Africa served as calibration data. Results: The model estimated that 28.7% (IQR: 27.4-28.9%) of MSM were HIV positive in 2010. By simulating a counterfactual HIV epidemic in South Africa, where HIV only spreads via male-male sex, we observe a decline in HIV incidence occurring in MSM by 56% over the period of 1990-2010, relative to the historical reality of HIV spreading via heterosexual and male-male sex. Analogously, HIV prevalence among MSM in 2010 under the counterfactual scenario reached only 10.0% (IQR 2.8- 17.4%), substantially less than HIV prevalence estimates from samples of MSM in South Africa. Conclusion: Roughly half of the HIV infections among MSM in South Africa can be attributed to the high levels of HIV prevalence in the general population. Scale up of interventions to target high risk behaviours with male partners should dispel possible misconceptions of bisexually active or heterosexual MSM as lower risk partners, relative to those MSM in gay communities.
Open Access
Estimation of adult antiretroviral treatment coverage in South Africa
(2009) Adam, Muhammad Aarif; Johnson, Leigh F
Objectives: To estimate the annual numbers of individuals receiving antiretroviral treatment in South Africa up to mid-2008, and the coverage of antiretroviral treatment in adults according to various definitions of need. Methods: Antiretroviral coverage is defined as the number of patients receiving antiretroviral treatment at a point in time, divided by the number needing treatment. Numbers of patients receiving antiretroviral treatment are estimated from public sector data and data provided by disease management programmes and NGO programmes. The unmet need for treatment in adults is estimated using a Markov model of HIV progression in adults, combined with estimates of annual new HIV infections from a national AIDS and demographic model. Results: By the middle of 2008, 547 000 adults and children were receiving antiretroviral treatment in South Africa, with the public health sector accounting for 78% of this total. Using the current Department of Health criteria for defining antiretroviral eligibility (CD4+ count <200/μl or WHO stage 4), antiretroviral coverage in adults was 38.4% in 2008, up from 4.9% in 2004. Coverage increases to 52.6% if eligibility is based on WHO stage 4 only, but reduces to 21.2% if the South African HIV Clinicians Society guidelines are used to define eligibility. Coverage in 2007 varied between provinces, from 14.6% in Free State to 58.3% in the Western Cape. Conclusions: Significant progress has been made in expanding access to antiretroviral treatment in South Africa since 2004, but there remains a substantial unmet need for treatment in adults.
Open Access
Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study
(Public Library of Science, 2012) Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F
Morna Cornell and colleagues investigate differences in mortality for HIV-positive men and women on antiretroviral therapy in South Africa.
Open Access
Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa
(2022-03-09) Nyemba, Dorothy C.; Peters, Remco P H; Medina-Marino, Andrew; Klausner, Jeffrey D; Ngwepe, Phuti; Myer, Landon; Johnson, Leigh F; Joseph Davey, Dvora L
Background Sexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes. Methods We combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics. Results Among 619 women, 61% (n = 380) were from Tshwane District and 39% (n = 239) from Cape Town; 79% (n = 486) were women living with HIV. The prevalence of any STI was 37% (n = 228); C. trachomatis, 26% (n = 158), T. vaginalis, 18% (n = 120) and N. gonorrhoeae, 6% (n = 40). There were 93% (n = 574) singleton live births, 5% (n = 29) miscarriages and 2% (n = 16) stillbirths. Among the live births, there were 1% (n = 3) neonatal deaths, 7% (n = 35) low birthweight in full-term babies and 10% (n = 62) preterm delivery. There were 24% (n = 146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95–2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89–5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04–2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09–3.08), were each independently associated with the composite adverse outcome in women living with HIV. Conclusion Treated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation.
Open Access
Increased alpha-9 human papillomavirus species viral load in human immunodeficiency virus positive women
(2014-01-31) Mbulawa, Zizipho Z; Johnson, Leigh F; Marais, Dianne J; Gustavsson, Inger; Moodley, Jennifer R; Coetzee, David; Gyllensten, Ulf; Williamson, Anna-Lise
Abstract Background Persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR-HPV viral load are associated with the development of cancer. This study investigated the effect of human immunodeficiency virus (HIV) co-infection, HIV viral load and CD4 count on the HR-HPV viral load; and also investigated the predictors of cervical abnormalities. Methods Participants were 292 HIV-negative and 258 HIV-positive women. HR-HPV viral loads in cervical cells were determined by the real-time polymerase chain reaction. Results HIV-positive women had a significantly higher viral load for combined alpha-9 HPV species compared to HIV-negative women (median 3.9 copies per cell compared to 0.63 copies per cell, P = 0.022). This was not observed for individual HPV types. HIV-positive women with CD4 counts >350/μl had significantly lower viral loads for alpha-7 HPV species (median 0.12 copies per cell) than HIV-positive women with CD4 ≤350/μl (median 1.52 copies per cell, P = 0.008), but low CD4 count was not significantly associated with increased viral load for other HPV species. High viral loads for alpha-6, alpha-7 and alpha-9 HPV species were significant predictors of abnormal cytology in women. Conclusion HIV co-infection significantly increased the combined alpha-9 HPV viral load in women but not viral loads for individual HPV types. High HR-HPV viral load was associated with cervical abnormal cytology.
Open Access
The interaction between HIV and other sexually transmitted infections in South Africa: a model-based evaluation
(2008) Johnson, Leigh F; Dorrington, Rob; Bradshaw, Debbie
Sexually transmitted infections (STIs) have been shown to increase the probability of HIV transmission, but there remains much uncertainty regarding the role of STI treatment in HIV prevention. This thesis aims to develop a mathematical model to estimate the prevalence of STIs in South Africa, the contribution of STIs to the spread of HIV, and the effects of changes in sexual behaviour and changes in STI treatment. A deterministic model is developed to simulate the transmission of HIV and six other STIs (syphilis, genital herpes, chancroid, gonorrhoea, chlamydial infection and trichomoniasis), as well as the incidence of bacterial vaginosis and vaginal candidiasis in women. The model is fitted to national HIV prevalence survey data, STI prevalence data from sentinel surveys and data from sexual behaviour surveys, using Bayesian techniques. Model results suggest that South Africa has some of the highest STI prevalence levels in the world, but that certain STIs â€“ notably syphilis, chancroid, gonorrhoea and trichomoniasis â€“ have declined in prevalence since the mid-1990s, following the introduction of syndromic management programmes and increases in condom use. STIs account for more than half of new HIV infections, and genital herpes is the most significant STI promoting the transmission of HIV. Syndromic management programmes reduced HIV incidence in South Africa by 3-10% over the decade following their introduction (1994-2004). Further reductions in HIV incidence could be achieved by promoting patient-initiated treatment of genital herpes, by addressing rising levels of drug resistance in gonococcal isolates, and by encouraging prompt health seeking for STIs. Concurrent partnerships are a major factor driving HIV transmission, accounting for 74-87% of new HIV infections over the 1990-2000 period. Halving unprotected sex in non-spousal relationships would reduce HIV incidence over the 2010 -2020 period by 32-43%. This thesis contributes to the understanding of HIV/AIDS epidemiology in South Africa by quantifying the contribution of various behavioural and biological factors to HIV transmission. This thesis also high lights several opportunities for reducing the future incidence of HIV. In addition, this thesis advances the assessment of uncertainty in STI models by proposing a Bayesian approach to incorporating sexual behaviour data and STI prevalence data into the parameter estimation process
Open Access
An investigation into the extent of uncertainty surrounding estimates of the impact of HIV/AIDS in South Africa
(Academy of Science of South Africa, 2007) Johnson, Leigh F; Dorrington, Rob E; Matthews, Alan P
HIV / AIDS statistics have been the source of much controversy in South Africa, but often the extent of uncertainty around these estimates is ignored. There is need for an assessment of the range of uncertainty around often-quoted HIV / AIDS statistics. This analysis determines ranges of uncertainty around the inputs and outputs of the ASSA2002 AIDS and Demographic model of the South African HIV / AIDS epidemic, using a generalized likelihood uncertainty estimation approach. A sample of 500 parameter combinations was drawn by weighting randomly generated parameter combinations by likelihood functions defined on the basis of four South African HIV / AIDS data sets. The estimated number of HIV infections in mid-2005 was 5.1 million (95% prediction interval: 4.2-6.0 million), equivalent to an HIV prevalence rate of 11.1% (9.1-13.1%). Between mid-2004 and mid-2005, the estimated number of new HIV infections was 490 000 (370 000-590 000) and the estimated number of AIDS deaths was 320 000 (270 000-380 000). The posterior mean HIV survival time was estimated to be 11.5 years (95% credibility interval: 10.0-12.9 years), longer than estimated for elsewhere in the developing world. This analysis confirms that South Africa is experiencing a severe HIV / AIDS epidemic, and suggests that HIV / AIDS epidemiology in the country probably differs from that elsewhere in Africa.
Open Access
Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study
(Public Library of Science, 2013) Estill, Janne; Egger, Matthias; Johnson, Leigh F; Gsponer, Thomas; Wandeler, Gilles; Davies, Mary-Ann; Boulle, Andrew; Wood, Robin; Garone, Daniela; Stringer, Jeffrey S A
Objectives Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference. Design: Mathematical modelling study based on data from ART programmes. METHODS: We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained. RESULTS: RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality. CONCLUSIONS: VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.
Open Access
Precarious transition: a mortality study of South African ex-miners
(BioMed Central, 2018-07-11) Bloch, Kim; Johnson, Leigh F; Nkosi, Mlindeli; Ehrlich, Rodney
Background Despite their burden of a triple epidemic of silicosis, tuberculosis and HIV infection, little is known about the mortality experience of miners from the South African mining industry once they leave employment. Such information is important because of the size and dispersion of this population across a number of countries and the progressive nature of these diseases. Methods This study included 306,297 South African miners who left the industry during 2001–2013. The study aimed to calculate crude and standardised mortality rates, identify secular trends in mortality and model demographic and occupational risk factors for mortality. Results Crude mortality rates peaked in the first year after exit (32.8/1000 person-years), decreasing with each year from exit. Overall mortality was 20% higher than in the general population. Adjusted annual mortality halved over the 12 year period. Mortality predictors were being a black miner [adjusted hazard ratio (aHR) 3.30; 95% confidence interval (CI) 3.15–3.46]; underground work (aHR 1.33; 95% CI 1.28–1.39); and gold aHR 1.15 (95% CI 1.12–1.19) or multiple commodity employment (aHR 1.15; 95% CI 1.11–1.19). Conclusions This is the first long-term mortality assessment in the large ex-miner population from the South African mining industry. Mortality patterns follow that of the national HIV-tuberculosis epidemic and antiretroviral treatment availability. However, ex-miners have further elevated mortality and a very high mortality risk in the year after leaving the workforce. Coordinated action between the mining industry, governments and non-governmental organisations is needed to reduce the impact of this precarious transition.
Open Access
Steady growth in antiretroviral treatment provision by disease management and community treatment programmes
(2007) Johnson, Leigh F; McLeod, Heather D
Although access to highly active antiretroviral treatment (HAART) in the South African public health sector is closely monitored, much remains unknown regarding the numbers of HIV-positive individuals receiving HAART outside the public health sector. Access to HAART in the private health sector is probably considerably better than in the public health sector, as private sector patients can often afford the costs of HAART, and many are beneficiaries of medical schemes, which are required to provide HAART to eligible beneficiaries as a prescribed minimum benefit. An investigation conducted in 2005 found that by the middle of 2005, at least 50 000 South Africans were receiving HAART through disease management programmes (DMPs), workplace treatment programmes (all of which are administered by DMPs) or community treatment programmes. This investigation was repeated in 2006, with the objective of estimating the numbers of people receiving HAART by mid-2006 and the rate of growth in numbers on treatment between 2005 and 2006.
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The effect of educational attainment and other factors on HIV risk in South African women: results from antenatal surveillance, 2000-2005
(2009) Johnson, Leigh F; Dorrington, Rob E; Bradshaw, Debbie; du Plessis, Hendrika; Makubalo, Lindiwe
Objectives: To assess the effect of educational attainment and other factors on the risk of HIV in pregnant South African women. Design: Repeated cross-sectional surveys. Methods: Pregnant women attending public antenatal clinics were tested for HIV annually between 2000 and 2005, and provided demographic information. Logistic regression models were applied separately to the data collected in each year, to identify factors associated with HIV infection. Data from all years were combined in a logistic regression model that tested for trends in HIV prevalence. Results: Amongst women aged 15–24 years, HIV risk in those who had completed secondary education was significantly lower than in those who had only primary education, in all years except 2000. HIV risk increased by 8% per annum (odds ratio 1.08, 95% confidence interval 1.04–1.12) in young women with no secondary education but did not increase in young women with secondary education. In women aged 25–49 years, HIV risk increased over the 2000–2005 period, at all levels of educational attainment, and did not differ between women with completed secondary education and women with only primary education. Conclusion: Together with other evidence, this study suggests that higher educational attainment did not protect against HIV in the early stages of the South African HIV/AIDS epidemic. In recent years, the risk of HIV infection in young South African women with completed secondary education has reduced significantly relative to that in young women with primary education, suggesting that HIV prevention strategies may have been more effective in more educated women.

Browsing by Author "Johnson, Leigh F"

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