Longitudinal evolution of the HIV effective reproduction number following sequential expansion of treatment as prevention and pre-exposure prophylaxis in British Columbia, Canada: a population-level programme evaluation.

BACKGROUND: Treatment as prevention and pre-exposure prophylaxis (PrEP) are key strategies in the control of HIV/AIDS. We aimed to characterise the longitudinal effects of antiretroviral therapy (ART), followed by treatment as prevention and the addition of PrEP, on the HIV effective reproduction number (Re) in British Columbia, Canada. METHODS: This population-level programme evaluation used data from the Drug Treatment Program of the British Columbia Centre for Excellence in HIV/AIDS (Vancouver, British Columbia, Canada). We also used estimates of HIV incidence and prevalence from the Public Health Agency of Canada, data on the number of new HIV diagnoses per year from the British Columbia Centre for Disease Control, and mortality data from the British Columbia Vital Statistics Agency. Data were obtained from 1985 until 2022, depending on the database source. Outcomes were the annual HIV prevalence, HIV incidence, number of new HIV diagnoses, number of people living with HIV on ART, HIV/AIDS-related and all-cause mortality rates, the HIV incidence-to-all-cause-mortality ratio, and Re. We calculated the modified effective reproduction number (Rme) using two thresholds of viral suppression and compared these values with Re. FINDINGS: We found a 95% decline in HIV/AIDS-related mortality and a 91% decrease in HIV incidence over the study period. The Re progressively declined from 1996 to 2022; however, from 1996 to 2017, Rme remained stable (>1) when calculated for people living with HIV with unsuppressed viraemia, suggesting that treatment as prevention reduces HIV incidence by decreasing the pool of individuals who are potentially able to transmit the virus. From 2018 to 2022, a decline in the estimated Re and Rme (<1) was observed regardless of whether we considered all people living with HIV or only those who were virologically unsuppressed. This finding suggests that PrEP decreases HIV incidence by reducing the number of susceptible individuals in the community, independently of viral suppression. INTERPRETATION: Our results show the synergy between generalised treatment as prevention and targeted PrEP in terms of decreasing HIV incidence. These findings support the incorporation of longitudinal monitoring of Re at a programmatic level to identify opportunities for the optimisation of treatment-as-prevention and PrEP programmes. FUNDING: British Columbia Ministry of Health, Health Canada, Public Health Agency of Canada, Vancouver Coastal Health, Vancouver General Hospital Foundation, Genome British Columbia, and the Canadian Institutes of Health Research.

Update on treatment as prevention of HIV illness, death, and transmission: sub-Saharan Africa HIV financing and progress towards the 95-95-95 target.

PURPOSE OF REVIEW: After over 40 years, the HIV pandemic is amongst the deadliest in history - 100% fatal without treatment, HIV has infected over 84 million people, and has caused over 40 million deaths. Global HIV spending between 2000 and 2015 totaled over a half trillion dollars. Delays in harnessing scientific advances, including 'test and treat' and treatment as prevention of illness, death, and transmission (TasP) provide a cautionary tale applicable to other pandemics. Resource allocation has also been problematic with many highest burden countries spending less than 50% on care and treatment. RECENT FINDINGS: Between 2002 and 2021, over $94 billion was budgeted for HIV in 40 sub-Saharan African countries, with 19 countries over $1 billion. In 2021, 8.1 million (32%) People Living with HIV (PLHIV) are still not on treatment; viral suppression data, the most important programme success indicator, is unavailable for 50% of countries. Of 19 countries with at least one billion dollars budgeted, seven have below 80% ART coverage, leaving 3.5 million (29%) of PLHIV off treatment and vulnerable to illness, death, and transmitting the virus to partners and children. SUMMARY: With additional funding and improved efficiency, achieving the 95-95-95 target to diagnose 95% of all HIV-positive individuals, provide antiretroviral therapy (ART) for 95% of those diagnosed and achieve viral suppression for 95% of those treated by 2030 is feasible and the humane pathway towards ending the HIV pandemic.

Human immunodeficiency virus funding and access to treatment in sub-Saharan Africa.

Human immunodeficiency virus (HIV) treatment prevents illness, death, and transmission. The 90-90-90 disease control target is only 73% of people living with HIV virally suppressed. For 2010 to 2019, we abstracted HIV funding data for 40 countries in sub-Saharan Africa (70% of global HIV burden and >99% of HIV burden in the region in 2018). During 2010-2019, there was ∼$52 billion funding for 40 countries (99% Africa HIV burden). Domestic funding ranged from $0 to $3.2 billion. PEPFAR funding was $32 billion (average $1.4 billion; range $0.089-4.3 billion) among 22 countries. Global Fund averaged $306 million ($1.9 million to $1.1 billion) for 40 countries. Among PLHIV, known HIV status averaged 80% (11% to 94%). ART coverage averaged 64% (9% to 90%). Viral suppression among PLHIV ranged from 8% to 87%. Of the 40 countries, 21 reported under 60% of PLHIV to be on treatment and 13 did not report viral suppression for 2018. Achieving 90-90-90 is feasible in challenging settings if resources are used efficiently. Despite the significant investment in the HIV response, many countries have not reached the 90-90-90 target. Greater attention to efficiency and prioritizing important targets will be required to end AIDS in Africa.

Treatment as prevention trials and ending AIDS: what do we know, when did we know it, and what do we do now?

PURPOSE OF REVIEW: HIV remains a significant global public health problem. Treatment as prevention of HIV and TB illness, death and transmission was proposed in 2006 as a means to end the HIV epidemic. We review the results of the treatment as prevention trials. RECENT FINDINGS: Some of the trials struggled with delivering services, however, most demonstrate that it is feasible to achieve at least the 90-90-90 target by scaling access to test-and-treat at the community level and by extension at the district or national level. Patients, if offered, will start and stay on immediate treatment even without symptoms. Community-based multidisease prevention campaigns have significant impact, especially for hard-to-reach men. Earlier treatment impacts illness and death including from HIV-associated tuberculosis. Test-and treat impacts transmission, however, some of the community cluster trials had difficulty showing an impact on incidence. Most trials showed incidence reduction in line with the level of viral suppression and suggest that achieving 95-95-95 is an important means to accelerate the end of the epidemic. SUMMARY: TasP trial findings, HIV and TB program data, and PHIA study trend data will likely confirm that reaching at least 95-95-95 is both feasible and a key element in ending the epidemic.

Structural Design and Data Requirements for Simulation Modelling in HIV/AIDS: A Narrative Review.

Born out of a necessity for fiscal sustainability, simulation modeling is playing an increasingly prominent role in setting priorities for combination implementation strategies for HIV treatment and prevention globally. The design of a model and the data inputted into it are central factors in ensuring credible inferences. We executed a narrative review of a set of dynamic HIV transmission models to comprehensively synthesize and compare the structural design and the quality of evidence used to support each model. We included 19 models representing both generalized and concentrated epidemics, classified as compartmental, agent-based, individual-based microsimulation or hybrid in our review. We focused on four structural components (population construction; model entry, exit and HIV care engagement; HIV disease progression; and the force of HIV infection), and two analytical components (model calibration/validation; and health economic evaluation, including uncertainty analysis). While the models we reviewed focused on a variety of individual interventions and their combinations, their structural designs were relatively homogenous across three of the four focal components, with key structural elements influenced by model type and epidemiological context. In contrast, model entry, exit and HIV care engagement tended to differ most across models, with some health system interactions-particularly HIV testing-not modeled explicitly in many contexts. The quality of data used in the models and the transparency with which the data was presented differed substantially across model components. Representative and high-quality data on health service delivery were most commonly not accessed or were unavailable. The structure of an HIV model should ideally fit its epidemiological context and be able to capture all efficacious treatment and prevention services relevant to a robust combination implementation strategy. Developing standardized guidelines on evidence syntheses for health economic evaluation would improve transparency and help prioritize data collection to reduce decision uncertainty.

Developing a dynamic HIV transmission model for 6 U.S. cities: An evidence synthesis.

BACKGROUND: Dynamic HIV transmission models can provide evidence-based guidance on optimal combination implementation strategies to treat and prevent HIV/AIDS. However, these models can be extremely data intensive, and the availability of good-quality data characterizing regional microepidemics varies substantially within and across countries. We aim to provide a comprehensive and transparent description of an evidence synthesis process and reporting framework employed to populate and calibrate a dynamic, compartmental HIV transmission model for six US cities. METHODS: We executed a mixed-method evidence synthesis strategy to populate model parameters in six categories: (i) initial HIV-negative and HIV-infected populations; (ii) parameters used to calculate the probability of HIV transmission; (iii) screening, diagnosis, treatment and HIV disease progression; (iv) HIV prevention programs; (v) the costs of medical care; and (vi) health utility weights for each stage of HIV disease progression. We identified parameters that required city-specific data and stratification by gender, risk group and race/ethnicity a priori and sought out databases for primary analysis to augment our evidence synthesis. We ranked the quality of each parameter using context- and domain-specific criteria and verified sources and assumptions with our scientific advisory committee. FINDINGS: To inform the 1,667 parameters needed to populate our model, we synthesized evidence from 59 peer-reviewed publications and 24 public health and surveillance reports and executed primary analyses using 11 data sets. Of these 1,667 parameters, 1,517 (91%) were city-specific and 150 (9%) were common for all cities. Notably, 1,074 (64%), 201 (12%) and 312 (19%) parameters corresponded to categories (i), (ii) and (iii), respectively. Parameters ranked as best- to moderate-quality evidence comprised 39% of the common parameters and ranged from 56%-60% across cities for the city-specific parameters. We identified variation in parameter values across cities as well as within cities across risk and race/ethnic groups. CONCLUSIONS: Better integration of modelling in decision making can be achieved by systematically reporting on the evidence synthesis process that is used to populate models, and by explicitly assessing the quality of data entered into the model. The effective communication of this process can help prioritize data collection of the most informative components of local HIV prevention and care services in order to reduce decision uncertainty and strengthen model conclusions.

Why Maximizing Quality-Adjusted Life Years, rather than Reducing HIV Incidence, Must Remain Our Objective in Addressing the HIV/AIDS Epidemic.

With efficacious behavioral, biomedical, and structural interventions available, combination implementation strategies are being implemented to combat HIV/AIDS across settings internationally. However, priority statements from national and international bodies make it unclear whether the objective should be the reduction in HIV incidence or the maximization of health, most commonly measured with quality-adjusted life years (QALYs). Building off a model-based evaluation of HIV care interventions in British Columbia, Canada, we compare the optimal sets of interventions that would be identified using HIV infections averted, and QALYs as the primary outcome in a cost-effectiveness analysis. We found an explicit focus on averting new infections undervalues the health benefits derived from antiretroviral therapy, resulting in suboptimal and potentially harmful funding recommendations.

90-90-90 HIV targets: implications for HIV-associated tuberculosis.

PURPOSE OF REVIEW: The HIV and Mycobacterium tuberculosis syndemic remains a major global public health threat. HIV and tuberculosis (TB) global targets have been set. Success will depend on achieving combined disease control. We explore current policy, economic investment, and disease control strategies for HIV, TB, and HIV-associated TB. We review published HIV, TB, and HIV-associated TB data for 30 WHO priority countries and propose a comprehensive HIV and TB care continua. RECENT FINDINGS: In 2016, people living with HIV (PLHIV) on antiretroviral treatment (ART) ranged from 13 to 84%; viral suppression ranged from 21 to 79%. Only 5% of PLHIV without TB reported a course of isoniazid preventive therapy (IPT). TB treatment success (2015) ranged from 34 to 94%. Data for the combined indicators: TB treatment success and viral suppression and IPT and ART for PLHIV are not collected. Reported 2003-2017 global international and domestic resources for TB and HIV-associated TB averaged $2.9 billion per year; cumulative total was $43 billion. SUMMARY: Integrating HIV and TB control efforts including monitoring and evaluation systems will be necessary to end both TB and HIV. A comprehensive HIV and TB continuum supports integrated, comprehensive HIV and TB disease control efforts focused on improving both individual and public health.

Two diseases, same person: moving toward a combined HIV and tuberculosis continuum of care.

The human immunodeficiency virus (HIV) and Mycobacterium tuberculosis syndemic remains a global public health threat. Separate HIV and tuberculosis (TB) global targets have been set; however, success will depend on achieving combined disease control objectives and care continua. The objective of this study was to review available policy, budgets, and data to reconceptualize TB and HIV disease control objectives by combining HIV and TB care continua. For 22 World Health Organization (WHO) TB and TB/HIV priority countries, we used 2015 data from the HIV90-90-90watch website, UNAIDS AIDSinfo, and WHO 2016 and 2017 Global TB Reports. Global resources available in TB and HIV/TB activities for 2003-2017 were collected from publicly available sources. In 22 high-burden countries, people living with HIV on antiretroviral therapy ranged from 9 to 70%; viral suppression was 38-63%. TB treatment success ranged from 71 to 94% with 14 (81% HIV/TB burden) countries above 80% TB treatment success. From 2003 to 2017, reported global international and domestic resources for HIV-associated TB and TB averaged $2.85 billion per year; the total for 2003-2017 was 43 billion dollars. Reviewing combined HIV and TB targets demonstrate disease control progress and challenges. Using an integrated HIV and TB continuum supports HIV and TB disease control efforts focused on improving both individual and public health.

Progress and prospects for the control of HIV and tuberculosis in South Africa: a dynamical modelling study.

BACKGROUND: In September, 2016, South Africa adopted a policy of providing antiretroviral treatment to everyone infected with HIV irrespective of their CD4 cell count. Studies of universal treatment and expanded prevention of HIV differ widely in their projections of effects and the associated costs, so we did this analysis to attempt to find a consensus. METHODS: We used data on HIV from the Joint UN Programme on HIV and AIDS (UNAIDS) from 1988 to 2013 and from data from WHO on tuberculosis from 1980 to to 2013 to fit a dynamical model to time trends in HIV prevalence, antiretroviral therapy (ART) coverage, and tuberculosis notification rates in South Africa. We then used the model to estimate current trends and project future patterns in HIV prevalence and incidence, AIDS-related mortality, and tuberculosis notification rates, and we used data from the South African National AIDS Council to assess current and future costs under different combinations of treatment and prevention approaches. We considered two treatment strategies: the Constant Effort strategy, in which people infected with HIV continue to start treatment at the rate in 2016, and the Expanded Treatment and Prevention (ETP) strategy, in which testing rates are increased, treatment is started immediately after HIV is detected, and prevention programmes are expanded. FINDINGS: Our estimates show that HIV incidence among adults aged 15 years or older fell from 2·3% per year in 1996 to 0·65% per year in 2016, AIDS-related mortality decreased from 1·4% per year in 2006 to 0·37% per year in 2016, and both continue to fall at a relative rate of 17% per year. Our model shows that maintenance of Constant Effort will have a substantial effect on HIV but will not end AIDS, whereas ETP could end AIDS by 2030, with incidence of HIV and AIDs-related mortality rates both at less than one event per 1000 adults per year. Under ETP the annual cost of health care and prevention will increase from US$2·3 billion in 2016 to $2·9 billion in 2018, then decrease to $1·7 billion in 2030 and $0·9 billion in 2050. Over the next 35 years, the expansion of treatment will avert an additional 3·8 million new infections, save 1·1 million lives, and save $3·2 billion compared with continuing Constant Effort up to 2050. Expansion of prevention, including provision of pre-exposure prophylaxis, condom distribution, and male circumcision, could avert a further 150 000 new infections, save 5000 lives, and cost an additional $5·7 billion compared with Constant Effort. INTERPRETATION: Our results suggest that South Africa is on track to reduce HIV incidence and AIDS-related mortality substantially by 2030, saving both lives and money. Success will depend on high rates of HIV testing, ART delivery and adherence, good patient monitoring and support, and data to monitor progress. FUNDING: None.

Status and methodology of publicly available national HIV care continua and 90-90-90 targets: A systematic review.

BACKGROUND: In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS) issued treatment goals for human immunodeficiency virus (HIV). The 90-90-90 target specifies that by 2020, 90% of individuals living with HIV will know their HIV status, 90% of people with diagnosed HIV infection will receive antiretroviral treatment (ART), and 90% of those taking ART will be virally suppressed. Consistent methods and routine reporting in the public domain will be necessary for tracking progress towards the 90-90-90 target. METHODS AND FINDINGS: For the period 2010-2016, we searched PubMed, UNAIDS country progress reports, World Health Organization (WHO), UNAIDS reports, national surveillance and program reports, United States President's Emergency Plan for AIDS Relief (PEPFAR) Country Operational Plans, and conference presentations and/or abstracts for the latest available national HIV care continuum in the public domain. Continua of care included the number and proportion of people living with HIV (PLHIV) who are diagnosed, on ART, and virally suppressed out of the estimated number of PLHIV. We ranked the described methods for indicators to derive high-, medium-, and low-quality continuum. For 2010-2016, we identified 53 national care continua with viral suppression estimates representing 19.7 million (54%) of the 2015 global estimate of PLHIV. Of the 53, 6 (with 2% of global burden) were high quality, using standard surveillance methods to derive an overall denominator and program data from national cohorts for estimating steps in the continuum. Only nine countries in sub-Saharan Africa had care continua with viral suppression estimates. Of the 53 countries, the average proportion of the aggregate of PLHIV from all countries on ART was 48%, and the proportion of PLHIV who were virally suppressed was 40%. Seven countries (Sweden, Cambodia, United Kingdom, Switzerland, Denmark, Rwanda, and Namibia) were within 12% and 10% of achieving the 90-90-90 target for "on ART" and for "viral suppression," respectively. The limitations to consider when interpreting the results include significant variation in methods used to determine national continua and the possibility that complete continua were not available through our comprehensive search of the public domain. CONCLUSIONS: Relatively few complete national continua of care are available in the public domain, and there is considerable variation in the methods for determining progress towards the 90-90-90 target. Despite bearing the highest HIV burden, national care continua from sub-Saharan Africa were less likely to be in the public domain. A standardized monitoring and evaluation approach could improve the use of scarce resources to achieve 90-90-90 through improved transparency, accountability, and efficiency.

National HIV Care Continua for Key Populations.

We reviewed published national HIV care continua for men who have sex with men (MSM), people who inject drugs (PWID), and female sex workers (FSWs) to track progress toward the 90-90-90 target. We searched the Internet, PubMed, surveillance reports, United Nations Programme on HIV/AIDS country reports, US President's Emergency Plan for AIDS Relief country/regional operational plans, and conference abstracts for the continua and graded them on quality. We found 12 continua for MSM, 7 for PWID, and 5 for FSW from 12 countries. HIV diagnosis, antiretroviral therapy coverage, and viral suppression varied between (1) 5% and 85%, 2% and 73%, and 1% and 72%, respectively for MSM; (2) 54% and 96%, 14% and 80%, and 8% and 68%, respectively for PWID; and (3) 27% and 63%, 8% and 16%, and 2% and 14%, respectively for FSW. Two countries, using data from national cohorts, were high quality. There are limited key population continua in the public domain. Of the few available, none have achieved 90-90-90. Improved monitoring and evaluation of key population continua is necessary to achieve the 90-90-90 target.