Introduction
UNAIDS’ goal of ending AIDS by 2030 is unreachable without better targeting of testing, prevention and care. Female sex workers (FSW) in Zimbabwe are at high risk of HIV acquisition and ...transmission. Here, we report on collated programme and research data from Zimbabwe's national sex work programme. We also assess the potential for wider population impact of FSW programmes by modelling the impact on HIV incidence of eliminating transmission through FSW (i.e. calculate the population attributable fraction of incidence attributable to sex work).
Methods
Descriptive analyses of individual‐level programme data collected from FSW between 2009 and June 2018 are triangulated with data collected through 37 respondent driven sampling surveys from 19 sites in Zimbabwe 2011 to 2017. We describe programme coverage, uptake, retention and patterns of sex work behaviour and gaps in service provision. An individual‐level stochastic simulation model is used to reconstruct the epidemic and then the incidence compared with the counter‐factual trend in incidence from 2010 had transmission through sex work been eliminated from that date.
Results
Sisters has reached >67,000 FSW since 2009, increasing attendance as number of sites, programme staff and peer educators were increased. Over 57% of all FSW estimated to be working in Zimbabwe in 2017 (n = 40,000) attended the programme at least once. The proportion of young FSW reached has increased with introduction of the “Young Sisters programme.” There are no clear differences in pattern of sex work across settings. Almost all women report condom use with clients at last sex (95%); however, consistent condom use with clients in the last month varies from 52% to 95% by site. Knowledge of HIV‐positive status has increased from 48 to 78% between 2011 and 2016, as has prevalence of ART use among diagnosed women (29 to 67%). Although subject to uncertainty, modelling suggests that 70% (90% range: 32%, 93%) of all new infections in Zimbabwe from 2010 are directly or indirectly attributable to transmission via sex work.
Conclusions
It is feasible to increase coverage and impact of sex work programming through community‐led scale‐up of evidence‐based interventions. Eliminating transmission through commercial sex would likely have a substantial impact on new infections occurring more widely across Zimbabwe.
Introduction
The 90‐90‐90 targets set by the United Nations aspire to 73% of people living with HIV (PLHIV) being virally suppressed by 2020. Using the HIV Synthesis Model, we aim to mimic the ...epidemic in Zimbabwe and make projections to assess whether Zimbabwe is on track to meet the 90‐90‐90 targets and assess whether recently proposed UNAIDS HIV transition metrics are likely to be met.
Methods
We used an approximate Bayesian computation approach to identify model parameter values which result in model outputs consistent with observed data, evaluated using a calibration score. These parameter values were then used to make projections to 2020 to compare with the 90‐90‐90 targets and other key indicators. We also calculated HIV transition metrics proposed by UNAIDS (percentage reduction in new HIV infections and AIDS‐related mortality from 2010 to 2020, absolute rate of new infections and AIDS‐related mortality, incidence–mortality ratio and incidence–prevalence ratios).
Results
After calibration, there was general agreement between modelled and observed data. The median predicted outcomes in 2020 were: proportion of PLHIV (aged 15 to 65) diagnosed 0.91 (90% uncertainty range 0.87, 0.94) (0.84 men, 0.95 women); of those diagnosed, proportion on treatment 0.92 (0.90, 0.93); of those receiving treatment, proportion with viral suppression 0.86 (0.81, 0.91). This results in 72% of PLHIV having viral suppression in 2020. We estimated a percentage reduction of 36.5% (13.7% increase to 67.4% reduction) in new infections from 2010 to 2020, and of 30.4% (9.7% increase to 56.6% reduction) in AIDS‐related mortality (UNAIDS target 75%). The modelled absolute rates of HIV incidence and AIDS‐related mortality in 2020 were 5.48 (2.26, 9.24) and 1.93 (1.31, 2.71) per 1000 person‐years respectively. The modelled incidence–mortality ratio and incidence–prevalence ratios in 2020 were 1.05 (0.46, 1.66) and 0.009 (0.004, 0.013) respectively.
Conclusions
Our model was able to produce outputs that are simultaneously consistent with an array of observed data and predicted that while the 90‐90‐90 targets are within reach in Zimbabwe, increased efforts are required in diagnosing men in particular. Calculation of the HIV transition metrics suggest increased efforts are needed to bring the HIV epidemic under control.
Introduction
As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost‐effective. To guide their HIV testing programmes, countries require appropriate metrics ...that can be measured. The cost‐per‐diagnosis is potentially a useful metric.
Methods
We simulated a series of setting‐scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual‐based model and projected forward from 2018 under two policies: (i) a minimum package of “core” testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core‐testing as above plus additional testing beyond this (“additional‐testing”), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost‐per‐diagnosis and the incremental cost‐effectiveness ratio (ICER) of the additional‐testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars).
Results
There was a strong graded relationship between the cost‐per‐diagnosis and the ICER. Overall, the ICER was below $500 per‐DALY‐averted (the cost‐effectiveness threshold used in primary analysis) so long as the cost‐per‐diagnosis was below $315. This threshold cost‐per‐diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional‐testing did not appear cost‐effective even at a cost‐per‐diagnosis of below $50, while restricting to men additional‐testing was cost‐effective up to a cost‐per‐diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost‐effective fell to $256 when the cost‐effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum.
Conclusions
For testing programmes in low‐income settings in southern African there is an extremely strong relationship between the cost‐per‐diagnosis and the cost‐per‐DALY averted, indicating that the cost‐per‐diagnosis can be used to monitor the cost‐effectiveness of testing programmes.
Chemotherapy in AL (primary or light chain) amyloidosis is associated with improved survival, but its effect on renal outcome has not been examined systematically. The purpose of this study was to ...evaluate the effect of chemotherapy on clinical outcome among patients with renal AL amyloidosis.
We evaluated factors influencing survival among 923 patients with renal AL amyloidosis observed during a 21-year period, including 221 patients who became dialysis dependent. Factors associated with renal outcome were analyzed, including serum free light chain (FLC) response to chemotherapy using a simple subtraction formula applicable to all stages of chronic kidney disease. Patient survival and graft survival were analyzed in 21 renal transplantation recipients.
Median survival from diagnosis for the whole cohort was 35.2 months. Magnitude of FLC response with chemotherapy was strongly and independently associated with overall survival (P < .001) and renal outcome. Evaluable patients achieving more than 90% FLC response had a significantly higher rate of renal responses and lower rate of renal progression compared with patients achieving a 50% to 90% response, whose renal outcomes were, in turn, better than patients achieving less than 50% FLC response (P < .001). Median survival from dialysis dependence was 39.0 months, and median survival from renal transplantation was 89.0 months.
Renal outcome and overall outcome in AL amyloidosis are strongly associated with FLC response to chemotherapy and are best among patients achieving more than 90% suppression of the amyloidogenic monoclonal component. Survival on dialysis was substantially superior to that previously reported, and renal transplantation should be considered in selected patients with AL amyloidosis with end-stage renal disease.
The COVID-19 pandemic has caused widespread disruptions including to health services. In the early response to the pandemic many countries restricted population movements and some health services ...were suspended or limited. In late 2020 and early 2021 some countries re-imposed restrictions. Health authorities need to balance the potential harms of additional SARS-CoV-2 transmission due to contacts associated with health services against the benefits of those services, including fewer new HIV infections and deaths. This paper examines these trade-offs for select HIV services.
We used four HIV simulation models (Goals, HIV Synthesis, Optima HIV and EMOD) to estimate the benefits of continuing HIV services in terms of fewer new HIV infections and deaths. We used three COVID-19 transmission models (Covasim, Cooper/Smith and a simple contact model) to estimate the additional deaths due to SARS-CoV-2 transmission among health workers and clients. We examined four HIV services: voluntary medical male circumcision, HIV diagnostic testing, viral load testing and programs to prevent mother-to-child transmission. We compared COVID-19 deaths in 2020 and 2021 with HIV deaths occurring now and over the next 50 years discounted to present value. The models were applied to countries with a range of HIV and COVID-19 epidemics.
Maintaining these HIV services could lead to additional COVID-19 deaths of 0.002 to 0.15 per 10,000 clients. HIV-related deaths averted are estimated to be much larger, 19-146 discounted deaths per 10,000 clients.
While there is some additional short-term risk of SARS-CoV-2 transmission associated with providing HIV services, the risk of additional COVID-19 deaths is at least 100 times less than the HIV deaths averted by those services. Ministries of Health need to take into account many factors in deciding when and how to offer essential health services during the COVID-19 pandemic. This work shows that the benefits of continuing key HIV services are far larger than the risks of additional SARS-CoV-2 transmission.
Mathematical models are increasingly used to inform HIV policy and planning. Comparing estimates obtained using different mathematical models can test the robustness of estimates and highlight ...research gaps. As part of a larger project aiming to determine the optimal allocation of funding for HIV services, in this study we compare projections from five mathematical models of the HIV epidemic in South Africa: EMOD-HIV, Goals, HIV-Synthesis, Optima, and Thembisa.
The five modelling groups produced estimates of the total population, HIV incidence, HIV prevalence, proportion of people living with HIV who are diagnosed, ART coverage, proportion of those on ART who are virally suppressed, AIDS-related deaths, total deaths, and the proportion of adult males who are circumcised. Estimates were made under a "status quo" scenario for the period 1990 to 2040. For each output variable we assessed the consistency of model estimates by calculating the coefficient of variation and examining the trend over time.
For most outputs there was significant inter-model variability between 1990 and 2005, when limited data was available for calibration, good consistency from 2005 to 2025, and increasing variability towards the end of the projection period. Estimates of HIV incidence, deaths in people living with HIV, and total deaths displayed the largest long-term variability, with standard deviations between 35 and 65% of the cross-model means. Despite this variability, all models predicted a gradual decline in HIV incidence in the long-term. Projections related to the UNAIDS 95-95-95 targets were more consistent, with the coefficients of variation below 0.1 for all groups except children.
While models produced consistent estimates for several outputs, there are areas of variability that should be investigated. This is important if projections are to be used in subsequent cost-effectiveness studies.
The UK Collaborative HIV Cohort (UK CHIC) is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently) 13 large clinics in the UK but does not ...collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC) collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone.
Women in UK CHIC receiving HIV-clinical care in 1996-2009, were found in the NSHPC dataset by initially 'linking' records with identical date-of-birth, linked records were then accepted as a genuine 'match', if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n = 8932). Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009). There was bias towards matching women with repeat pregnancies (35.9% (741/2063) of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869) of women in NSHPC only) and matching women HIV diagnosed before their first reported pregnancy (54.8% (1131/2063) compared to 47.7% (3278/6869), respectively).
Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.
Hepatitis B virus (HBV) infection is an increasingly important cause of morbidity and mortality in HIV-infected adults. This study aimed to determine the prevalence and incidence of HBV in the UK ...CHIC Study, a multicentre observational cohort.
12 HIV treatment centres were included. Of 37,331 patients, 27,450 had at least one test (HBsAg, anti-HBs or anti-HBc) result post-1996 available. 16,043 were white, 8,130 black and 3,277 other ethnicity. Route of exposure was homosexual sex 15,223 males, heterosexual sex 3,258 males and 5,384 females, injecting drug use 862 and other 2,723. The main outcome measures used were the cumulative prevalence and the incidence of HBV coinfection. HBV susceptible patients were followed up until HBsAg and/or anti-HBc seroconversion incident infection, evidence of vaccination or last visit. Poisson regression was used to determine associated factors. 25,973 had at least one HBsAg test result. Participants with HBsAg results were typically MSM (57%) and white (59%) (similar to the cohort as a whole). The cumulative prevalence of detectable HBsAg was 6.9% (6.6 to 7.2%). Among the 3,379 initially HBV-susceptible patients, the incidence of HBV infection was 1.7 (1.5 to 1.9)/100 person-years. Factors associated with incident infection were older age and IDU. The main limitation of the study was that 30% of participants did not have any HBsAg results available. However baseline characteristics of those with results did not differ from those of the whole cohort. Efforts are on-going to improve data collection.
The prevalence of HBV in UK CHIC is in line with estimates from other studies and low by international standards. Incident infection continued to occur even after entry to the cohort, emphasising the need to ensure early vaccination.
To describe predictors of pregnancy and changes in pregnancy incidence among HIV-positive women accessing HIV clinical care.
Data were obtained through the linkage of two separate studies: the UK ...Collaborative HIV Cohort study (UK CHIC), a cohort of adults attending 13 large HIV clinics; and the National Study of HIV in Pregnancy and Childhood (NSHPC), a national surveillance study of HIV-positive pregnant women. Pregnancy incidence was measured using the proportion of women in UK CHIC with a pregnancy reported to NSHPC. Generalized estimating equations were used to identify predictors of pregnancy and assess changes in pregnancy incidence in 2000-2009.
The number of women accessing care at UK CHIC sites increased as did the number of pregnancies. Older women were less likely to have a pregnancy adjusted relative rate (aRR) 0.44 per 10 year increment in age, 95% confidence interval (CI) (0.41-0.46), P < 0.001 as were women with CD4 cell count less than 200 cells/μl compared with CD4 cell count 200-350 cells/μl aRR 0.65 (0.55-0.77), P < 0.001 and women of white ethnicity compared with women of black African ethnicity aRR 0.67 (0.57-0.80), P < 0.001. The likelihood that women had a pregnancy increased over the study period aRR 1.05 (1.03-1.07), P < 0.001). The rate of change did not significantly differ according to age group, antiretroviral therapy use, CD4 group or ethnicity.
The pregnancy rate among women accessing HIV clinical care increased in 2000-2009. HIV-positive women with, or planning, a pregnancy require a high level of care and this is likely to continue and increase as more women of older age have pregnancies.
Interventions based around objective measurement of adherence to antiretroviral drugs for HIV have potential to improve adherence and to enable differentiation of care such that clinical visits are ...reduced in those with high adherence. It would be useful to understand the approximate upper limit of cost that could be considered for such interventions of a given effectiveness in order to be cost effective. Such information can guide whether to implement an intervention in the light of a trial showing a certain effectiveness and cost.
An individual-based model, calibrated to Zimbabwe, which incorporates effects of adherence and resistance to antiretroviral therapy, was used to model the potential impact of adherence monitoring-based interventions on viral suppression, death rates, disability adjusted life years and costs. Potential component effects of the intervention were: enhanced average adherence when on ART, reduced risk of ART discontinuation, and reduced risk of resistance acquisition. We considered a situation in which viral load monitoring is not available and one in which it is. In the former case, it was assumed that care would be differentiated based on the adherence level, with fewer clinic visits in those demonstrated to have high adherence. In the latter case, care was assumed to be primarily differentiated according to viral load level. The maximum intervention cost required to be cost effective was calculated based on a cost effectiveness threshold of $500 per DALY averted.
In the absence of viral load monitoring, an adherence monitoring-based intervention which results in a durable 6% increase in the proportion of ART experienced people with viral load < 1000 cps/mL was cost effective if it cost up to $50 per person-year on ART, mainly driven by the cost savings of differentiation of care. In the presence of viral load monitoring availability, an intervention with a similar effect on viral load suppression was cost-effective when costing $23-$32 per year, depending on whether the adherence intervention is used to reduce the level of need for viral load measurement.
The cost thresholds identified suggest that there is clear scope for adherence monitoring-based interventions to provide net population health gain, with potential cost-effective use in situations where viral load monitoring is or is not available. Our results guide the implementation of future adherence monitoring interventions found in randomized trials to have health benefit.
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