Publications
21 results found
Smith J, Garnett G, Hallett T, 2021, The potential impact of long-acting cabotegravir for HIV prevention in South Africa: a mathematical modelling study, Journal of Infectious Diseases, Vol: 224, Pages: 1179-1186, ISSN: 0022-1899
BackgroundAlthough effective, some oral pre-exposure prophylaxis (PrEP) users face barriers to adherence using daily pills, which could be reduced by long-acting formulations. Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials.MethodsWe use a mathematical model of the HIV epidemic in South Africa to simulate CAB LA uptake by population groups with different levels of HIV risk. We compare the trajectory of the HIV epidemic until 2050 with and without CAB LA to estimate the impact of the intervention.ResultsDelivering CAB LA to 10% of the adult population could avert more than 15% of new infections from 2023 to 2050. The impact would be lower but more efficient if delivered to populations at higher HIV risk: 127 person-years of CAB LA use would be required to avert one HIV infection within 5 years if used by all adults and 47 person-years if used only by the highest risk women.ConclusionsIf efficacious, a CAB LA intervention could have a substantial impact on the course of the HIV epidemic in South Africa. Uptake by those at the highest risk of infection, particularly young women, could improve the efficiency of any intervention.
Smith J, Beacroft L, Abdullah F, et al., 2020, Responding to the ECHO trial results: modelling the potential impact of changing contraceptive method mix on HIV and reproductive health in South Africa, Journal of the International AIDS Society, Vol: 23, Pages: 1-10, ISSN: 1758-2652
Introduction: Some observational data suggest that the progestogen injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase a woman’s risk of HIV acquisition but a randomised clinical trial did not find a statistically significant increase in HIV risk for women using DMPA compared to two other methods. However, it could not rule out up to 30% increased HIV risk for DMPA users. We evaluate changes to contraceptive method mix in South Africa under different assumptions about the existence and strength of a possible undetected relationship between DMPA use and HIV risk. Methods: A mathematical model was developed to simulate the ongoing HIV epidemic and contraceptive method mix in South Africa to estimate how changes in method mix could impact HIV- and reproductive health-related outcomes. We made different assumptions about the relationship between DMPA use and HIV risk, from no relationship to a 30% increase in HIV risk for women using DMPA. Scenario analyses were used to investigate the impact of switching away from DMPA predominance to new patterns of contraceptive use.Results: In South Africa, the HIV-related benefits of reduced DMPA use could be as great as the harms of increased adverse reproductive health outcomes over twenty years, if DMPA did increase the risk of HIV acquisition by a relative hazard of infection of 1.1 or greater. A reduction in DMPA use among HIV-positive women would have no benefit in terms of HIV infections, but would incur additional negative reproductive health outcomes. The most important driver of adverse reproductive health outcomes is the proportion of women who switch away from DMPA to no contraceptive method.Conclusions: If there is any real increased HIV risk for DMPA users that has not been detected by the recent randomised trial, a reduction in DMPA use could reduce the ongoing number of new HIV infections. However, such a change would place more women at risk at adverse reproductive health effects. I
Hogan A, Jewell B, Sherrard-Smith E, et al., 2020, Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: a modelling study, The Lancet Global Health, Vol: 8, Pages: e1132-e1141, ISSN: 2214-109X
Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings.Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics.Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic.Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC
Jewell B, Mudimu E, Stover J, et al., 2020, Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models, The Lancet HIV, Vol: 7, Pages: e629-e640, ISSN: 2405-4704
Background: The COVID-19 epidemic could lead to the disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimates that more than two thirds of the 37.9 million (32.7-44.0 million) people living with HIV reside in 2018. We set out to predict the potential effects of such disruptions on HIV-related deaths and new infections.Methods: Five well-described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, Imperial College model, EMOD) were each used to estimate the effect of various potential disruptions to HIV prevention, testing and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months from 1 April 2020. Disruptions affecting 20%, 50% and 100% of the population were considered. In further analyses shorter term disruptions and the possibility of reductions in sexual activity during disruptions were considered. Findings: A six-month interruption of supply of antiretroviral (ARV) drugs across 50% of the population of people living with HIV on treatment would be expected to lead to a 1.63-fold (median across models; range 1.39 to 1.87) increase in HIV-related deaths over a one year period compared to with no disruption. In sub-Saharan Africa this amounts to an excess of 296,000 (median over model estimates, range 229,000 – 420,000) HIV deaths should such a high level of disruption occur. There would also be an approximately 1.6-fold increase in mother to child transmission of HIV. While an interruption of supply of ARV drug would have by far the largest impact of any potential disruptions, effects of poorer clinical care due to over-stretched health facilities, interruptions of supply of other drugs such as cotrimoxazole and suspension of HIV testing would all have significant population-level impact on mortality. Interruption to condom supplies and peer education would make populations more vulnerable to increases
Jewell BL, Smith JA, Hallett TB, 2020, Understanding the impact of interruptions to HIV services during the COVID-19 pandemic: A modelling study, EClinicalMedicine, Vol: 26, Pages: 1-7, ISSN: 2589-5370
BackgroundThere is concern that the COVID-19 pandemic could severely disrupt HIV services in sub-Saharan Africa. However, it is difficult to determine priorities for maintaining different elements of existing HIV services given widespread uncertainty.MethodsWe explore the impact of disruptions on HIV outcomes in South Africa, Malawi, Zimbabwe, and Uganda using a mathematical model, examine how impact is affected by model assumptions, and compare potential HIV deaths to those that may be caused by COVID-19 in the same settings.FindingsThe most important determinant of HIV-related mortality is an interruption to antiretroviral treatment (ART) supply. A three-month interruption for 40% of those on ART could cause a similar number of additional deaths as those that might be saved from COVID-19 through social distancing. An interruption for more than 6–90% of individuals on ART for nine months could cause the number of HIV deaths to exceed the number of COVID-19 deaths, depending on the COVID-19 projection. However, if ART supply is maintained, but new treatment, voluntary medical male circumcision, and pre-exposure prophylaxis initiations cease for 3 months and condom use is reduced, increases in HIV deaths would be limited to <2% over five years, although this could still be accompanied by a 7% increase in new HIV infections.InterpretationHIV deaths could increase substantially during the COVID-19 pandemic under reasonable worst-case assumptions about interruptions to HIV services. It is a priority in high-burden countries to ensure continuity of ART during the pandemic.FundingBill & Melinda Gates Foundation.
Jewell B, Smith JA, Hallett T, 2020, The Potential Impact of Interruptions to HIV Services: A Modelling Case Study for South Africa, Publisher: Cold Spring Harbor Laboratory
<jats:p>The numbers of deaths caused by HIV could increase substantially if the COVID-19 epidemic leads to interruptions in the availability of HIV services. We compare publicly available scenarios for COVID-19 mortality with predicted additional HIV-related mortality based on assumptions about possible interruptions in HIV programs. An interruption in the supply of ART for 40% of those on ART for 3 months could cause a number of deaths on the same order of magnitude as the number that are anticipated to be saved from COVID-19 through social distancing measures. In contrast, if the disruption can be managed such that the supply and usage of ART is maintained, the increase in AIDS deaths would be limited to 1% over five years, although this could still be accompanied by substantial increases in new HIV infections if there are reductions in VMMC, oral PrEP use, and condom availability.</jats:p>
Jewell BL, Smith JA, Padian NS, et al., 2020, ECHO: context and limitations, The Lancet, Vol: 395, Pages: e25-e26, ISSN: 0140-6736
Beacroft L, Smith JA, Hallett TB, 2019, What impact could DMPA use have had in South Africa and how might its continued use affect the future of the HIV epidemic?, Journal of the International AIDS Society, Vol: 22, Pages: 1-6, ISSN: 1758-2652
IntroductionSome studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa.MethodsWe simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The “With Effect” scenario assumes that DMPA increases susceptibility to HIV infection by 1.20‐fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The “No Effect” scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV‐related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic.ResultsA causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037.ConclusionsIf there is a causal association between DMPA use and HIV risk, it could have subs
Sharma M, Smith JA, Farquhar C, et al., 2018, Assisted partner notification services are cost-effective for decreasing HIV burden in western Kenya, AIDS, Vol: 32, Pages: 233-241, ISSN: 0269-9370
Background: Assisted partner services (aPS) or provider notification for sexual partners of persons diagnosed HIV positive can increase HIV testing and linkage in Sub-Saharan Africa and is a high yield strategy to identify HIV-positive persons. However, its cost-effectiveness is not well evaluated.Methods: Using effectiveness and cost data from an aPS trial in Kenya, we parameterized an individual-based, dynamic HIV transmission model. We estimated costs for both a program scenario and a task-shifting scenario using community health workers to conduct the intervention. We simulated 200 cohorts of 500 000 individuals and projected the health and economic effects of scaling up aPS in a region of western Kenya (formerly Nyanza Province).Findings: Over a 10-year time horizon with universal antiretroviral therapy (ART) initiation, implementing aPS in western Kenya was projected to reach 12.5% of the population and reduce incident HIV infections by 3.7%. In sexual partners receiving aPS, HIV-related deaths were reduced by 13.7%. The incremental cost-effectiveness ratio of aPS was $1094 (US dollars) (90% model variability $823–1619) and $833 (90% model variability $628–1224) per disability-adjusted life year averted under the program and task-shifting scenario, respectively. The incremental cost-effectiveness ratios for both scenarios fall below Kenya's gross domestic product per capita ($1358) and are therefore considered very cost-effective. Results were robust to varying healthcare costs, linkage to care rates, partner concurrency rates, and ART eligibility thresholds (≤350 cells/μl, ≤500 cells/μl, and universal ART).Interpretation: APS is cost-effective for reducing HIV-related morbidity and mortality in western Kenya and similar settings. Task shifting can increase program affordability.
Cremin I, McKinnon L, Kimani J, et al., 2017, PrEP for key populations in combination HIV prevention in Nairobi: a mathematical modelling study, LANCET HIV, Vol: 4, Pages: E214-E222, ISSN: 2352-3018
Smith JA, Heffron R, Butler AR, et al., 2016, Could misreporting of condom use explain the observed association between injectable hormonal contraceptives and HIV acquisition risk?, Contraception, Vol: 95, Pages: 424-430, ISSN: 0010-7824
OBJECTIVE: Some observational studies have suggested an association between the use of hormonal contraceptives (HC) and HIV acquisition. One major concern is that differential misreporting of sexual behavior between HC users and nonusers may generate artificially inflated risk estimates. STUDY DESIGN: We developed an individual-based model that simulates the South African HIV serodiscordant couples analyzed for HC-HIV risk by Heffron et al. (2012). We varied the pattern of misreporting condom use between HC users and nonusers and reproduced the trial data under the assumption that HC use is not associated with HIV risk. The simulated data were analyzed using Cox proportional hazards models, adjusting for the reported level of condom use. RESULTS: If HC users overreport condom use more than nonusers, an apparent excess risk could be observed even without any biological effect of HC on HIV acquisition. With 45% overreporting by HC users (i.e., 9 out of every 20 sex acts reported with condoms are actually unprotected) and accurate condom reporting by nonusers, a true null effect can be inflated to give an observed hazard ratio (HR̂) of 2.0. In a different population with lower overall reported condom use, artificially high HR̂s can only be generated if non-HC users underreport condom use. CONCLUSION: Differential condom misreporting can theoretically produce inflated HR̂ values for an association between HC and HIV even without a true association. However, to produce a doubling of HIV risk that is entirely spurious requires substantially different levels of misreporting among HC users and nonusers, which may be unrealistic. IMPLICATIONS: Considerably differential amounts of condom use misreporting by HC users and nonusers would be needed to produce entirely spurious observed levels of excess HIV acquisition risk among HC users when there is actually no true association.
Smith JA, Anderson SJ, Harris KL, et al., 2016, Maximising HIV prevention - balancing the opportunities of today with the promises of tomorrow: a modelling study, The Lancet HIV, Vol: 3, Pages: e289-e296, ISSN: 2352-3018
Background: Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years.Methods: We developed a mathematical model of the HIV epidemic in South Africa and formed assumptions about the costs and effects of a range of interventions, encompassing the further scale-up of existing interventions (promoting condom use, male circumcision, outreach testing and early ART initiation for all, and oral PrEP), the introduction of new interventions in the medium-term (offering intravaginal rings (IVR), long-acting antiretrovirals (LA-ARVS)) and long-term (vaccine, broadly neutralising antibodies (bNAbs)). We examined how available resources could be allocated across these interventions to achieve maximal impact, and assessed how this would be affected by the failure of the interventions to be developed or scaled up.Findings: If all the above-listed interventions are available, the optimal mix of interventions would place great emphasis on: (i) scale-up of male circumcision and outreach testing and ART initiation, as these are available immediately and are assumed to be low cost and/or highly efficacious; (ii) IVR targeted to sex workers; and (iii) vaccines, as these can achieve a high impact if scaled-up even if imperfectly efficacious. It would rely less on longer-term developments, such as LA-ARVS and bNAbs, unless the costs of these reduced. However, if it were not possible to scale up existing interventions to the extent assumed, greater emphasis would be placed on oral PrEP, IVR and LA-ARVs. The long-term impact on the epidemic is most affected by scale-up of existing interventions and the successful development of a vaccine.Interpretation: With current information, a strategic approach in which limited resources are used to maximise
Smith JA, Sharma M, Levin C, et al., 2015, Cost-effectiveness of community-based strategies to strengthen the continuum of HIV care in rural South Africa: a health economic modelling analysis, Lancet HIV, Vol: 2, Pages: e159-e168, ISSN: 2352-3018
BackgroundHome HIV counselling and testing (HTC) achieves high coverage of testing and linkage to care compared with existing facility-based approaches, particularly among asymptomatic individuals. In a modelling analysis we aimed to assess the effect on population-level health and cost-effectiveness of a community-based package of home HTC in KwaZulu-Natal, South Africa.MethodsWe parameterised an individual-based model with data from home HTC and linkage field studies that achieved high coverage (91%) and linkage to antiretroviral therapy (80%) in rural KwaZulu-Natal, South Africa. Costs were derived from a linked microcosting study. The model simulated 10 000 individuals over 10 years and incremental cost-effectiveness ratios were calculated for the intervention relative to the existing status quo of facility-based testing, with costs discounted at 3% annually.FindingsThe model predicted implementation of home HTC in addition to current practice to decrease HIV-associated morbidity by 10–22% and HIV infections by 9–48% with increasing CD4 cell count thresholds for antiretroviral therapy initiation. Incremental programme costs were US$2·7 million to $4·4 million higher in the intervention scenarios than at baseline, and costs increased with higher CD4 cell count thresholds for antiretroviral therapy initiation; antiretroviral therapy accounted for 48–87% of total costs. Incremental cost-effectiveness ratios per disability-adjusted life-year averted were $1340 at an antiretroviral therapy threshold of CD4 count lower than 200 cells per μL, $1090 at lower than 350 cells per μL, $1150 at lower than 500 cells per μL, and $1360 at universal access to antiretroviral therapy.InterpretationCommunity-based HTC with enhanced linkage to care can result in increased HIV testing coverage and treatment uptake, decreasing the population burden of HIV-associated morbidity and mortality. The incremental cost-effectiveness ratios are less tha
Smith J, Nyamukapa C, Gregson S, et al., 2014, The Distribution of Sex Acts and Condom Use within Partnerships in a Rural Sub-Saharan African Population, PLOS ONE, Vol: 9, ISSN: 1932-6203
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Butler AR, Smith JA, Polis CB, et al., 2013, Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk, AIDS, Vol: 27, Pages: 105-113, ISSN: 0269-9370
Background: Some, but not all, observational studies have suggested an increase in the risk of HIV acquisition for women using injectable hormonal contraception (IHC).Methods: We used country-level data to explore the effects of reducing IHC use on the number of HIV infections, the number of live births and the resulting net consequences on AIDS deaths and maternal mortality for each country.Results: High IHC use coincides with high HIV incidence primarily in southern and eastern Africa. If IHC increases the risk of HIV acquisition, this could generate 27 000–130 000 infections per year globally, 87–88% of which occur in this region. Reducing IHC use could result in fewer HIV infections but also a substantial increase in live births and maternal mortality in countries with high IHC use, high birth rates and high maternal mortality: mainly southern and eastern Africa, South-East Asia, and Central and South America. For most countries, the net impact of reducing IHC use on maternal and AIDS-related deaths is dependent on the magnitude of the assumed IHC–HIV interaction.Conclusions: If IHC use increases HIV acquisition risk, reducing IHC could reduce new HIV infections; however, this must be balanced against other important consequences, including unintended pregnancy, which impacts maternal and infant mortality. Unless the true effect size approaches a relative risk of 2.19, it is unlikely that reductions in IHC could result in public health benefit, with the possible exception of those countries in southern Africa with the largest HIV epidemics.
Thomson EC, Smith JA, Klenerman P, 2011, The natural history of early hepatitis C virus evolution; lessons from a global outbreak in human immunodeficiency virus-1-infected individuals, Journal of General Virology, Vol: 92, Pages: 2227-2236, ISSN: 1465-2099
New insights into the early viral evolution and cellular immune response during acute hepatitis C virus (HCV) infection are being gained following a global outbreak in human immunodeficiency virus-1 (HIV)-positive men who have sex with men. Cross-sectional and longitudinal sequence analysis at both the population and individual level have facilitated tracking of the HCV epidemic across the world and enabled the development of tests of viral diversity in individual patients in order to predict spontaneous clearance of HCV and response to treatment. Immunological studies in HIV-positive cohorts have highlighted the role of the CD4+ T-cell response in the control of early HCV infection and will increase the opportunity for the identification of protective epitopes that could be used in future vaccine development.
Thomson EC, Fleming VM, Main J, et al., 2011, Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men, GUT, Vol: 60, Pages: 837-845, ISSN: 0017-5749
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Smith JA, Aberle JH, Fleming VM, et al., 2010, Dynamic Coinfection with Multiple Viral Subtypes in Acute Hepatitis C, JOURNAL OF INFECTIOUS DISEASES, Vol: 202, Pages: 1770-1779, ISSN: 0022-1899
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- Citations: 25
Lopman B, Cook A, Smith J, et al., 2010, Verbal autopsy can consistently measure AIDS mortality: a validation study in Tanzania and Zimbabwe, Journal of Epidemiology and Community Health, Vol: 64, Pages: 330-334, ISSN: 0143-005X
Background Verbal autopsy is currently the only option for obtaining cause of death information in most populations with a widespread HIV/AIDS epidemic.Methods With the use of a data-driven algorithm, a set of criteria for classifying AIDS mortality was trained. Data from two longitudinal community studies in Tanzania and Zimbabwe were used, both of which have collected information on the HIV status of the population over a prolonged period and maintained a demographic surveillance system that collects information on cause of death through verbal autopsy. The algorithm was then tested in different times (two phases of the Zimbabwe study) and different places (Tanzania and Zimbabwe).Results The trained algorithm, including nine signs and symptoms, performed consistently based on sensitivity and specificity on verbal autopsy data for deaths in 15–44-year-olds from Zimbabwe phase I (sensitivity 79%; specificity 79%), phase II (sensitivity 83%; specificity 75%) and Tanzania (sensitivity 75%; specificity 74%) studies. The sensitivity dropped markedly for classifying deaths in 45–59-year-olds.Conclusions Verbal autopsy can consistently measure AIDS mortality with a set of nine criteria. Surveillance should focus on deaths that occur in the 15–44-year age group for which the method performs reliably. Addition of a handful of questions related to opportunistic infections would enable other widely used verbal autopsy tools to apply this validated method in areas for which HIV testing and hospital records are unavailable or incomplete.
Hallett TB, Singh K, Smith JA, et al., 2008, Understanding the Impact of Male Circumcision Interventions on the Spread of HIV in Southern Africa, PLOS ONE, Vol: 3, ISSN: 1932-6203
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Smith J, Mushati P, Kurwa F, et al., 2007, Changing patterns of adult mortality as the HIV epidemic matures in Manicaland, eastern Zimbabwe, AIDS, Vol: 21, Pages: S81-S86, ISSN: 0269-9370
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- Citations: 11
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