Publications
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Vollmer M, Mishra S, Unwin H, et al., 2020, Report 20: A sub-national analysis of the rate of transmission of Covid-19 in Italy
Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28; 238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could lead to a resurgence in the number of deaths far greater than experienced in the current wave in several regions. Future increases in the number of deaths will lag behind the increase in transmission intensity and so a
Grassly N, Pons Salort M, Parker E, et al., 2020, Report 16: Role of testing in COVID-19 control
The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.
Becker ML, Bhattacharjee P, Blanchard JF, et al., 2019, Reply, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 81, Pages: e163-e165, ISSN: 1525-4135
Bhattacharjee P, Rego D, Musyoki H, et al., 2019, Evaluation of community-based HIV self-testing delivery strategies on reducing undiagnosed HIV infection, and improving linkage to prevention and treatment services, among men who have sex with men in Kenya: a programme science study protocol, BMC Public Health, Vol: 19, Pages: 1-13, ISSN: 1471-2458
BackgroundHIV prevalence among men having sex with men (MSM) in Kenya is 18.2%. Despite scale-up of HIV testing services, many MSM remain unaware of their HIV status and thus do not benefit from accessing HIV treatment or prevention services. HIV self-testing (HIVST) may help address this gap. However, evidence is limited on how, when, and in what contexts the delivery of HIVST to MSM could increase awareness of HIV status and lead to early linkage to HIV treatment and prevention.MethodsThe study will be embedded within existing MSM-focused community-based HIV prevention and treatment programmes in 3 counties in Kenya (Kisumu, Mombasa, Kiambu). The study is designed to assess three HIV testing outcomes among MSM, namely a) coverage b) frequency of testing and c) early uptake of testing. The study will adopt a mixed methods programme science approach to the implementation and evaluation of HIVST strategies via: (i) a baseline and endline bio-behavioural survey with 1400 MSM; (ii) a socio-sexual network study with 351 MSM; (iii) a longitudinal qualitative cohort study with 72 MSM; (iv) routine programme monitoring in three sites; (v) a programme-specific costing exercise; and (vi) mathematical modelling. This protocol evaluates the impact of community-based implementation of HIV self-testing delivery strategies among MSM in Kenya on reducing the undiagnosed MSM population, and time for linkage to prevention, treatment and care following HIV self-testing. Baseline data collection started in April 2019 and the endline data collection will start in July 2020.DiscussionThis study is one of the first programme science studies in Sub-Saharan Africa exploring the effectiveness of integrating HIVST interventions within already existing HIV prevention and treatment programmes for MSM in Kenya at scale. Findings from this study will inform national best approaches to scale up HIVST among MSM in Kenya.
Becker M, Musyoki H, Mishra S, et al., 2019, HIV prevalence in at-risk adolescent girls and young women in Kenya across locations associated with sex work, ISSTDR 2019, Publisher: BMJ Publishing Group, Pages: A311-A311, ISSN: 1368-4973
Pavlova D, Balakireva O, Cheuk E, et al., 2019, P702 Characterizing HIV-associated vulnerabilities among women engaged in transactional sex to design programs in Ukraine, STI & HIV World Congress (Joint Meeting of the 23rd ISSTDR and 20th IUSTI), Publisher: BMJ Publishing Group, Pages: A306-A307, ISSN: 1368-4973
Cheuk E, Leung S, Balakireva O, et al., 2019, P718 Risk and place: the association between hotspot typology and determinants of HIV risk among female sex workers in Ukraine, STI & HIV World Congress (Joint Meeting of the 23rd ISSTDR and 20th IUSTI), Publisher: BMJ Publishing Group, Pages: A312-A312, ISSN: 1368-4973
Becker M, Balakireva O, Herpai N, et al., 2019, HIV AND HCV AMONG CLIENTS OF FEMALE SEX WORKERS IN DNIPRO, UKRAINE, ISSTDR 2019, Publisher: BMJ PUBLISHING GROUP, Pages: A58-A58, ISSN: 1368-4973
Probert W, Hall M, Xi X, et al., 2019, Quantifying the contribution of different aged men and women to onwards transmission of HIV-1 in generalised epidemics in sub-Saharan Africa: A modelling and phylogenetics approach from the HPTN071 (PopART) trial, 10th IAS Conference on HIV Science, Publisher: JOHN WILEY & SONS LTD, Pages: 107-107
Herpai N, Becker M, Balakireva O, et al., 2019, ADOPTING A POLITICAL ECONOMY APPROACH TO HIV RESEARCH: A CASE STUDY OF ONGOING CONFLICT IN UKRAINE, ISSTDR 2019, Publisher: BMJ PUBLISHING GROUP, Pages: A127-A127, ISSN: 1368-4973
Becker M, Balakireva O, Pavlova D, et al., 2019, Assessing the influence of conflict on the dynamics of sex work and the HIV and HCV epidemics in Ukraine: protocol for an observational, ethnographic, and mathematical modeling study, BMC INTERNATIONAL HEALTH AND HUMAN RIGHTS, Vol: 19, ISSN: 1472-698X
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- Citations: 7
Cheuk E, Isac S, Musyoki H, et al., 2019, Informing HIV prevention programs for adolescent girls and young women: a modified approach to programmatic mapping and key population size estimation, JMIR Public Health and Surveillance, Vol: 5, Pages: 242-255, ISSN: 2369-2960
Background: Standard programmatic mapping involves identifying locations where key populations meet, profiling of these locations (hotspots), and estimating the key population size. Information gained from this method has been used for HIV programming—resource allocation, program planning, service delivery, and monitoring and evaluation—for people who inject drugs, men who have sex with men, and female sex workers (FSWs). With an increasing focus on adolescent girls and young women (AGYW) as a priority population for HIV prevention, programs need to know the location of and how to effectively reach individuals who are at increased risk for HIV but were conventionally considered part of the general population. We hypothesize that AGYW who engage in transactional and casual sex also congregate at sex work hotspots to meet sex partners. Therefore, we adapted the standard programmatic mapping approach to understand the geographic distribution and population size of AGYW at increased HIV risk in Mombasa County, Kenya.Objectives: The objectives are several-fold: (1) detail and compare the modified programmatic mapping approach used in this study to the standard approach, (2) estimate the number of young FSWs, (3) estimate the number of AGYW who congregate in sex work hotspots to meet sex partners other than clients, (4) estimate the overlap in sexual network in hotspots, (5) describe the distribution of sex work hotspots across Mombasa and its four subcounties, and (6) compare the distribution of hotspots that were known to the local HIV prevention program prior to this study and those newly identified.Methods: The standard programmatic mapping approach was modified to estimate the population of young women aged 14 to 24 years who visit sex work hotspots in Mombasa to meet partners for commercial, transactional, and casual sex.Results: We estimated that there were 11,777 FSWs (range 9265 to 14,290) in Mombasa in 2014 among whom 6127 (52.02%) were 14 to 24 year
Mulubwa C, Hensen B, Phiri MM, et al., 2019, Community based distribution of oral HIV self-testing kits in Zambia: a cluster-randomised trial nested in four HPTN 071 (PopART) intervention communities, Lancet HIV, Vol: 6, Pages: E81-E92, ISSN: 2405-4704
BackgroundThe HPTN 071 (PopART) cluster-randomised trial provided door-to-door HIV testing services to a large proportion of individuals residing in 21 intervention communities in Zambia and South Africa from 2014 to 2017 and reached the UNAIDS first 90 target among women in Zambia, yet gaps remained among men and young adults. This cluster-randomised study nested in the HPTN 071 (PopART) trial sought to increase knowledge of HIV status across all groups by offering the choice of oral HIV self-testing in addition to routine door-to-door HIV testing services.MethodsWe nested this cluster-randomised trial in four HTPN 071 (PopART) intervention communities in northern Zambia. 66 zones (clusters) in these communities were randomly allocated (1:1) to either oral HIV self-testing plus routine door-to-door HIV testing services (HIV self-testing group) or the PopART standard of care of door-to-door HIV testing services alone (non- HIV self-testing group) over a 3-month period. All individuals aged 16 years or older were eligible for HIV testing. Randomisation was achieved by randomly selecting one allocation from a list of 10 000 possible allocations during a public ceremony. In HIV self-testing zones, trained lay-counsellors (known as community HIV care providers) visited households and offered eligible individuals the choice of HIV testing using HIV self-testing or routine door-to-door HIV testing services. For individuals aged 18 years or older whose partner was absent during the household visit, an HIV self-test kit could be left for secondary distribution to the absent partner. The primary outcome was knowledge of HIV status (defined as self-reporting HIV positive to the community HIV care providers or accepting an offer of HIV testing services). Outcomes were measured among households that were first visited, and individuals first enumerated as a household member during the HIV self-testing intervention period. We analysed data at the individual level using population
Becker ML, Bhattacharjee P, Blanchard JF, et al., 2018, Vulnerabilities at First Sex and Their Association With Lifetime Gender-Based Violence and HIV Prevalence Among Adolescent Girls and Young Women Engaged in Sex Work, Transactional Sex, and Casual Sex in Kenya, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 79, Pages: 296-304, ISSN: 1525-4135
BACKGROUND:Adolescent girls and young women (AGYW) experience high rates of HIV early in their sexual life course. We estimated the prevalence of HIV-associated vulnerabilities at first sex, and their association with lifetime gender-based violence (GBV) and HIV. METHODS:We conducted a cross-sectional biobehavioral survey among AGYW (14-24 years) in Mombasa, Kenya in 2015. We compared the prevalence of first sex vulnerabilities across AGYW who self-identified as engaging in sex work (N = 408), transactional sex (N = 177), or casual sex (N = 714) and used logistic regression to identify age-adjusted associations between first sex vulnerabilities and outcomes (GBV after first sex; HIV). RESULTS:The median age at first sex was 16 years (interquartile range 14-18). A total of 43.6% received gifts or money at first sex; 41.2% and 11.2% experienced a coerced and forced first sex, respectively. First sex vulnerabilities were generally more common among AGYW in sex work. GBV (prevalence 23.8%) and HIV (prevalence 5.6%) were associated with first sex before age 15 [GBV adjusted odds ratio (AOR) 1.4, 95% confidence interval (CI): 1.0 to 1.9; HIV AOR 1.9, 95% CI: 1.1 to 1.3]; before or within 1 year of menarche (GBV AOR 1.3, 95% CI: 1.0 to 1.7; HIV AOR 2.1, 95% CI: 1.3 to 3.6); and receipt of money (GBV AOR 1.9, 95% CI: 1.4 to 2.5; HIV AOR 2.0, 95% CI: 1.2 to 3.4). CONCLUSIONS:HIV-associated vulnerabilities begin at first sex and potentially mediate an AGYW's trajectory of risk. HIV prevention programs should include structural interventions that reach AGYW early, and screening for a history of first sex vulnerabilities could help identify AGYW at risk of ongoing GBV and HIV.
Mountain E, Pickles M, Bhattacharjee P, et al., 2018, Experience of Violence Is Associated With HIV Prevention Uptake and HIV Infection Among Young Women Who Self-identify as Sex Workers in Mombasa, Kenya, HIV Research for Prevention Meeting (HIVR4P) - AIDS Vaccine, Microbicide and ARV-Based Prevention Science, Publisher: MARY ANN LIEBERT, INC, Pages: 234-234, ISSN: 0889-2229
Thomas RA, Burger R, Harper A, et al., 2017, Differences in health-related quality of life between HIV-positive and HIV-negative people in Zambia and South Africa: a cross-sectional baseline survey of the HPTN 071 (PopART) trial, The Lancet Global Health, Vol: 5, Pages: e1133-e1141, ISSN: 2214-109X
BackgroundThe life expectancy of HIV-positive individuals receiving antiretroviral therapy (ART) is approaching that of HIV-negative people. However, little is known about how these populations compare in terms of health-related quality of life (HRQoL). We aimed to compare HRQoL between HIV-positive and HIV-negative people in Zambia and South Africa.MethodsAs part of the HPTN 071 (PopART) study, data from adults aged 18–44 years were gathered between Nov 28, 2013, and March 31, 2015, in large cross-sectional surveys of random samples of the general population in 21 communities in Zambia and South Africa. HRQoL data were collected with a standardised generic measure of health across five domains. We used β-distributed multivariable models to analyse differences in HRQoL scores between HIV-negative and HIV-positive individuals who were unaware of their status; aware, but not in HIV care; in HIV care, but who had not initiated ART; on ART for less than 5 years; and on ART for 5 years or more. We included controls for sociodemographic variables, herpes simplex virus type-2 status, and recreational drug use.FindingsWe obtained data for 19 750 respondents in Zambia and 18 941 respondents in South Africa. Laboratory-confirmed HIV status was available for 19 330 respondents in Zambia and 18 004 respondents in South Africa; 4128 (21%) of these 19 330 respondents in Zambia and 4012 (22%) of 18 004 respondents in South Africa had laboratory-confirmed HIV. We obtained complete HRQoL information for 19 637 respondents in Zambia and 18 429 respondents in South Africa. HRQoL scores did not differ significantly between individuals who had initiated ART more than 5 years previously and HIV-negative individuals, neither in Zambia (change in mean score −0·002, 95% CI −0·01 to 0·001; p=0·219) nor in South Africa (0·000, −0·002 to 0·003; p=0·939). However, scores did differ between HIV-positive individu
Ratmann O, Hodcroft EB, Pickles M, et al., 2017, Phylogenetic tools for generalized HIV-1 epidemics: findings from the PANGEA-HIV methods comparison, Molecular Biology and Evolution, Vol: 34, Pages: 185-203, ISSN: 1537-1719
Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modeling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first 3 months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods’ development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention.
Ramachandran S, Mishra S, Condie N, et al., 2016, How do HIV-negative individuals in sub-Saharan Africa change their sexual risk behaviour upon learning their serostatus? A systematic review, Sexually Transmitted Infections, Vol: 92, Pages: 571-578, ISSN: 1472-3263
Objective: To determine whether, and how, sexual behaviour of HIV-negative individuals in Sub-Saharan Africa (SSA) changes upon learning their serostatus.Methods: We systematically reviewed the published literature using EMBASE and Medline to search for publications between 2004 and 2014. We included studies that quantified behaviour change (condom use, number of sexual partners or sex acts) following an HIV test in HIV-negative adults in SSA, and extracted relevant data including study characteristics and measurement type.Results: From 2185 unique citations, n=14 studies representing 22,390 participants met our inclusion criteria. We did not pool data due to marked heterogeneity in study outcome measures. The proportion of participants reporting consistent condom use (n=6) post-testing ranged from 7.6% greater, to 10.6% fewer, while “no condom use” (n=5) ranged from 40.0% less, to 0.7% more. Condom use in serodiscordant couples increased (n=3). Five studies measured the proportion reporting abstinence, finding an increase of 10.9% to a decrease of 5.3% post-testing. The post-testing change in the mean number of sex acts (n=3) ranged from a relative decrease of 15.7% to a relative increase of 9.4%. Two studies reported relative decreases in the mean number of sexual partners of 35.2% and 14.0%. Three studies examining serodiscordant primary relationships specifically all showed increases in extra-relational sex.Conclusions: With the exception of serodiscordant couples, there is variable evidence that awareness of one’s serostatus leads to substantial changes in risk behaviour among HIV-negative individuals. Further research is needed to estimate the behavioural impact of learning one’s serostatus in SSA.
Cheuk E, Mishra S, Gichangi P, et al., 2016, SUBSTANCE USE AND EXPERIENCE OF VIOLENCE AMONG YOUNG WOMEN ENGAGED IN CASUAL, TRANSACTIONAL, AND FORMAL SEX WORK IN MOMBASA, KENYA, Sexually Transmitted Diseases (STD) Prevention Conference, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: S157-S158, ISSN: 0148-5717
Heffernan A, Barber E, Thomas R, et al., 2016, Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa., PLOS One, Vol: 11, ISSN: 1932-6203
Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC) CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs) were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3%) of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness.
Herbeck JT, Mittler JE, Gottlieb GS, et al., 2016, Evolution of HIV virulence in response to widespread scale up of antiretroviral therapy: a modeling study, Virus Evolution, Vol: 2, ISSN: 2057-1577
There are global increases in the use of HIV antiretroviral therapy (ART), guided by clinical benefits of early ART initiation and the efficacy of treatment as prevention of transmission. Separately, it has been shown theoretically and empirically that HIV virulence can evolve over time; observed virulence levels may reflect an adaptive balance between infected lifespan and per-contact transmission rate. However, the potential effects of widespread ART usage on HIV virulence are unknown. To predict these effects, we used an agent-based stochastic model to simulate evolutionary trends in HIV virulence, using set point viral load as a proxy for virulence. We calibrated our model to prevalence and incidence trends of South Africa. We explored two distinct ART scenarios: (1) ART initiation based on HIV-infected individuals reaching a CD4 count threshold; and (2) ART initiation based on individual time elapsed since HIV infection (a scenario that mimics “universal testing and treatment” (UTT) aspirations). In each case, we considered a range in population uptake of ART. We found that HIV virulence is generally unchanged in scenarios of CD4-based initiation. However, with ART initiation based on time since infection, virulence can increase moderately within several years of ART rollout, under high coverage levels and early treatment initiation (albeit within the context of epidemics that are rapidly decreasing in size). Sensitivity analyses suggested the impact of ART on virulence is relatively insensitive to model calibration. Our modeling study suggests that increasing HIV virulence driven by UTT is likely not a major public health concern, but should be monitored in sentinel surveillance, in a manner similar to transmitted resistance to antiretroviral drugs.
Dureau J, Kalogeropoulos K, Vickerman P, et al., 2016, A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data, Journal of the Royal Statistical Society Series C - Applied Statistics, Vol: 65, Pages: 237-257, ISSN: 0035-9254
Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts.
Cori A, Pickles M, van Sighem A, et al., 2015, CD4+ cell dynamics in untreated HIV-1 infection: overall rates, and effects of age, viral load, sex and calendar time., AIDS, Vol: 29, Pages: 2435-2446, ISSN: 0269-9370
BACKGROUND: CD4 cell count is a key measure of HIV disease progression, and the basis of successive international guidelines for treatment initiation. CD4 cell dynamics are used in mathematical and econometric models for evaluating public health need and interventions. Here, we estimate rates of CD4 decline, stratified by relevant covariates, in a form that is clinically transparent and can be directly used in such models. METHODS: We analyse the AIDS Therapy Evaluation in the Netherlands cohort, including individuals with date of seroconversion estimated to be within 1 year and with intensive clinical follow-up prior to treatment initiation. Owing to the fact that CD4 cell counts are intrinsically noisy, we separate the analysis into long-term trends of smoothed CD4 cell counts and an observation model relating actual CD4 measurements to the underlying smoothed counts. We use a monotonic spline smoothing model to describe the decline of smoothed CD4 cell counts through categories CD4 above 500, 350-500, 200-350 and 200 cells/μl or less. We estimate the proportion of individuals starting in each category after seroconversion and the average time spent in each category. We examine individual-level cofactors which influence these parameters. RESULTS: Among untreated individuals, the time spent in each compartment was 3.32, 2.70, 5.50 and 5.06 years. Only 76% started in the CD4 cell count above 500 cells/μl compartment after seroconversion. Set-point viral load (SPVL) was an important factor: individuals with at least 5 log10 copies/ml took 5.37 years to reach CD4 cell count less than 200 cells/μl compared with 15.76 years for SPVL less than 4 log10 copies/ml. CONCLUSION: Many individuals already have CD4 cell count below 500 cells/μl after seroconversion. SPVL strongly influences the rate of CD4 decline. Treatment guidelines should consider measuring SPVL, whereas mathematical models should incorporate SPVL stratification.
Condie N, Ramachandran S, Pickles M, et al., 2015, The impact of a positive HIV diagnosis on sexual risk behaviour: A systematic review, Publisher: WILEY-BLACKWELL, Pages: 26-26, ISSN: 1464-2662
Ramachandran S, Condie N, Pickles M, et al., 2015, How do HIV-negative individuals in sub-Saharan Africa change their sexual risk behaviour upon learning their serostatus? A systematic review, Publisher: WILEY-BLACKWELL, Pages: 26-26, ISSN: 1464-2662
Boily M-C, Pickles M, Alary M, et al., 2015, What Really Is a Concentrated HIV Epidemic and What Does It Mean for West and Central Africa? Insights From Mathematical Modeling, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 68, Pages: S74-S82, ISSN: 1525-4135
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Jewell BL, Cremin I, Pickles M, et al., 2015, Estimating the cost-effectiveness of pre-exposure prophylaxis to reduce HIV-1 and HSV-2 incidence in HIV-serodiscordant couples in South Africa, PLOS One, Vol: 10, ISSN: 1932-6203
ObjectiveTo estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa.MethodsWe incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter.ResultsWe estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively – a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples.ConclusionAfter a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.
Shannon K, Strathdee SA, Goldenberg SM, et al., 2015, Global epidemiology of HIV among female sex workers: influence of structural determinants, The Lancet, Vol: 385, Pages: 55-71, ISSN: 0140-6736
Female sex workers (FSWs) bear a disproportionately large burden of HIV infection worldwide. Despite decades of research and programme activity, the epidemiology of HIV and the role that structural determinants have in mitigating or potentiating HIV epidemics and access to care for FSWs is poorly understood. We reviewed available published data for HIV prevalence and incidence, condom use, and structural determinants among this group. Only 87 (43%) of 204 unique studies reviewed explicitly examined structural determinants of HIV. Most studies were from Asia, with few from areas with a heavy burden of HIV such as sub-Saharan Africa, Russia, and eastern Europe. To further explore the potential effect of structural determinants on the course of epidemics, we used a deterministic transmission model to simulate potential HIV infections averted through structural changes in regions with concentrated and generalised epidemics, and high HIV prevalence among FSWs. This modelling suggested that elimination of sexual violence alone could avert 17% of HIV infections in Kenya (95% uncertainty interval [UI] 1–31) and 20% in Canada (95% UI 3–39) through its immediate and sustained effect on non-condom use) among FSWs and their clients in the next decade. In Kenya, scaling up of access to antiretroviral therapy among FSWs and their clients to meet WHO eligibility of a CD4 cell count of less than 500 cells per μL could avert 34% (95% UI 25–42) of infections and even modest coverage of sex worker-led outreach could avert 20% (95% UI 8–36) of infections in the next decade. Decriminalisation of sex work would have the greatest effect on the course of HIV epidemics across all settings, averting 33–46% of HIV infections in the next decade. Multipronged structural and community-led interventions are crucial to increase access to prevention and treatment and to promote human rights for FSWs worldwide.
Vassall A, Chandrashekar S, Pickles M, et al., 2014, Community mobilisation and empowerment interventions as part of HIV prevention for female sex workers in southern India: a cost-effectiveness analysis, PLOS One, Vol: 9, ISSN: 1932-6203
BackgroundMost HIV prevention for female sex workers (FSWs) focuses on individual behaviour change involving peer educators, condom promotion and the provision of sexual health services. However, there is a growing recognition of the need to address broader societal, contextual and structural factors contributing to FSW risk behaviour. We assess the cost-effectiveness of adding community mobilisation (CM) and empowerment interventions (eg. community mobilisation, community involvement in programme management and services, violence reduction, and addressing legal policies and police practices), to core HIV prevention services delivered as part of Avahan in two districts (Bellary and Belgaum) of Karnataka state, Southern India.MethodsAn ingredients approach was used to estimate economic costs in US$ 2011 from an HIV programme perspective of CM and empowerment interventions over a seven year period (2004–2011). Incremental impact, in terms of HIV infections averted, was estimated using a two-stage process. An ‘exposure analysis’ explored whether exposure to CM was associated with FSW’s empowerment, risk behaviours and HIV/STI prevalence. Pathway analyses were then used to estimate the extent to which behaviour change may be attributable to CM and to inform a dynamic HIV transmission model.FindingsThe incremental costs of CM and empowerment were US$ 307,711 in Belgaum and US$ 592,903 in Bellary over seven years (2004–2011). Over a 7-year period (2004–2011) the mean (standard deviation, sd.) number of HIV infections averted through CM and empowerment is estimated to be 1257 (308) in Belgaum and 2775 (1260) in Bellary. This translates in a mean (sd.) incremental cost per disability adjusted life year (DALY) averted of US$ 14.12 (3.68) in Belgaum and US$ 13.48 (6.80) for Bellary - well below the World Health Organisation recommended willingness to pay threshold for India. When savings from ART are taken into account, investments in CM an
Mountain E, Pickles M, Mishra S, et al., 2014, The HIV care cascade and antiretroviral therapy in female sex workers: implications for HIV prevention, EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, Vol: 12, Pages: 1203-1219, ISSN: 1478-7210
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