Dataset Information

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study.

ABSTRACT:

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.

SUBMITTER: Estill J

PROVIDER: S-EPMC3585414 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study.

Estill Janne J Egger Matthias M Johnson Leigh F LF Gsponer Thomas T Wandeler Gilles G Davies Mary-Ann MA Boulle Andrew A Wood Robin R Garone Daniela D Stringer Jeffrey S A JS Hallett Timothy B TB Keiser Olivia O

PloS one 20130228 2

<h4>Objectives</h4>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.<h4>Design</h4>Mathematical modelling study based on data from ART programmes.<h4>Methods</h4>We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline sce ...[more]

PMID: 23469035

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Project description:BACKGROUND:Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART. METHODS AND FINDINGS:Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness. CONCLUSIONS:ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality.

Project description:IntroductionDespite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence.MethodsWe constructed a multi-state model describing male-to-female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re-initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre-exposure prophylaxis (PrEP) for HIV-negative female ANC patients with HIV-diagnosed or unknown-status male partners. We estimated the percentage of within-couple, male-to-female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base-case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re-initiate ART and 0% of female ANC patients start PrEP.ResultsIncreasing uptake of any single strategy by 20 percentage points above base-case levels averted 10%-11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%-23% of transmissions, and with a 20-percentage-point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/re-initiation and 40% female PrEP use reduced incident infections by 45%.ConclusionsCombination HIV prevention strategies provided alongside ANC and sustained through the post-partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa.

Project description:BackgroundAs access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status.MethodsIn this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age.FindingsBetween Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older.InterpretationHealth services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV.FundingNational Institutes of Health (National Institute of Allergy and Infectious Diseases), US Agency for International Development, and South African Centre for Epidemiological Modelling and Analysis.

Project description:IntroductionMany countries in Africa are scaling up differentiated service delivery (DSD) models for HIV treatment, but most existing data systems do not describe the models in use. We surveyed organizations that were supporting DSD models in 2019 in Malawi, South Africa, and Zambia to describe the diversity of DSD models being implemented at that time.MethodsWe interviewed DSD model implementing organizations for descriptive information about each of the organization's models of care. We described the key characteristics of each model, including population of patients served, location of service delivery, frequency of interactions with patients, duration of dispensing, and cadre(s) of provider involved. To facilitate analysis, we refer to 1 organization supporting 1 model of care as an "organization-model."ResultsThe 34 respondents (8 in Malawi, 16 in South Africa, 10 in Zambia) interviewed described a total of 110 organization-models, which included 19 facility-based individual models, 21 out-of-facility-based individual models, 14 health care worker-led groups, and 3 client-led groups; jointly, these encompassed 12 specific service delivery strategies, such as multimonth dispensing, adherence clubs, home delivery, and changes to facility hours. Over two-thirds (n=78) of the organization-models were limited to clinically stable patients. Almost all organization-models (n=96) continued to provide clinical care at established health care facilities; medication pickup took place at facilities, external pickup points, and adherence clubs. Required numbers of provider interactions per year varied widely, from 2 to 12. Dispensing intervals were typically 3 or 6 months in Malawi and Zambia and 2 months in South Africa. Individual models relied more on clinical staff, while group models made greater use of lay personnel.ConclusionsAs of 2019, there was a large variety of differentiated service models being offered for HIV treatment in Malawi, South Africa, and Zambia, serving diverse patient populations.

Project description:BackgroundMpumalanga in South Africa is committed to eliminating malaria by 2018 and efforts are increasing beyond that necessary for malaria control. Differential Equation models may be used to study the incidence and spread of disease with an important benefit being the ability to enact exogenous change on the system to predict impact without committing any real resources. The model is a deterministic non-linear ordinary differential equation representation of the dynamics of the human population. The model is fitted to weekly data of treated cases from 2002 to 2008, and then validated with data from 2009 to 2012. Elimination-focused interventions such as the scale-up of vector control, mass drug administration, a focused mass screen and treat campaign and foreign source reduction are applied to the model to assess their potential impact on transmission.ResultsScaling up vector control by 10% and 20% resulted in substantial predicted decreases in local infections with little impact on imported infections. Mass drug administration is a high impact but short-lived intervention with predicted decreases in local infections of less that one infection per year. However, transmission reverted to pre-intervention levels within three years. Focused mass screen and treat campaigns at border-entry points are predicted to result in a knock-on decrease in local infections through a reduction in the infectious reservoir. This knock-on decrease in local infections was also predicted to be achieved through foreign source reduction. Elimination was only predicted to be possible under the scenario of zero imported infections in Mpumalanga.ConclusionsA constant influx of imported infections show that vector control alone will not be able to eliminate local malaria as it is insufficient to interrupt transmission. Both mass interventions have a large and immediate impact. Yet in countries with a large migrant population, these interventions may fail due to the reintroduction of parasites and their impact may be short-lived. While all strategies (in isolation or combined) contributed to decreasing local infections, none was predicted to decrease local infections to zero. The number of imported infections highlights the importance of reducing imported infections at source, and a regional approach to malaria elimination.

Dataset Information

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study.

Objectives

Design

Methods

Results

Conclusions

Publications

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study.

Similar Datasets

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