HIV treatment as prevention: contradictory perspectives from dynamic mathematical models.
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ABSTRACT:
SUBMITTER: Wu J
PROVIDER: S-EPMC4279253 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:Introduction:HIV viral load (VL) is accepted as a key biomarker in HIV transmission and pathogenesis. This paper presents a review of the role of VL testing in mathematical models for HIV prevention and treatment. Methods:A search for simulation models of HIV was conducted in PubMed, yielding a total of 1210 studies. Publications before the year 2000, studies involving animals and analyses that did not use mathematical simulations were excluded. The full text of eligible articles was sourced and information about the intervention and population being modelled, type of modelling approach and disease monitoring strategy was extracted. Results and discussion:A total of 279 studies related to HIV simulation models were included in the review, though only 17 (6%) included consideration of VL or VL testing and were evaluated in detail. Within the studies that included assessment of VL, routine monitoring was the focus, and usually in comparison to alternate monitoring strategies such as clinical or CD4 count-based monitoring. The majority of remaining models focus on the impact or delivery of antiretroviral therapy (n=68; 27%), pre-exposure prophylaxis (n=28; 11%) and/or HIV testing (n=24; 9%) on population estimates of HIV epidemiology and exclude consideration of VL. Few studies investigate or compare alternate VL monitoring frequencies, and only a small number of studies overall (3%) include consideration of vulnerable population groups such as pregnant women or infants. Conclusions:There are very few simulations of HIV treatment or prevention that include VL measures, despite VL being recognised as the key determinant of both transmission and treatment outcomes. With growing emphasis on VL monitoring as key tool for population-level HIV control, there is a clear need for simulations of HIV epidemiology based on VL.
| S-EPMC7042590 | biostudies-literature
Project description:BackgroundExpanding access to highly active antiretroviral therapy (HAART) has become an important approach to HIV prevention in recent years. Previous studies suggest that concomitant changes in risk behaviours may either help or hinder programs that use a Treatment as Prevention strategy.AnalysisWe consider HIV-related risk behaviour as a social contagion in a deterministic compartmental model, which treats risk behaviour and HIV infection as linked processes, where acquiring risk behaviour is a prerequisite for contracting HIV. The equilibrium behaviour of the model is analysed to determine epidemic outcomes under conditions of expanding HAART coverage along with risk behaviours that change with HAART coverage. We determined the potential impact of changes in risk behaviour on the outcomes of Treatment as Prevention strategies. Model results show that HIV incidence and prevalence decline only above threshold levels of HAART coverage, which depends strongly on risk behaviour parameter values. Expanding HAART coverage with simultaneous reduction in risk behaviour act synergistically to accelerate the drop in HIV incidence and prevalence. Above the thresholds, additional HAART coverage is always sufficient to reverse the impact of HAART optimism on incidence and prevalence. Applying the model to an HIV epidemic in Vancouver, Canada, showed no evidence of HAART optimism in that setting.ConclusionsOur results suggest that Treatment as Prevention has significant potential for controlling the HIV epidemic once HAART coverage reaches a threshold. Furthermore, expanding HAART coverage combined with interventions targeting risk behaviours amplify the preventive impact, potentially driving the HIV epidemic to elimination.
| S-EPMC3646049 | biostudies-literature
Project description:HIV-1 latency is a major barrier to curing infections with antiretroviral therapy and, consequently, to eliminating the disease globally. The establishment, maintenance, and potential clearance of latent infection are complex dynamic processes and can be best described with the help of mathematical models followed by experimental validation. Here, we review the use of viral dynamics models for HIV-1, with a focus on applications to the latent reservoir. Such models have been used to explain the multi-phasic decay of viral load during antiretroviral therapy, the early seeding of the latent reservoir during acute infection and the limited inflow during treatment, the dynamics of viral blips, and the phenomenon of post-treatment control. Finally, we discuss that mathematical models have been used to predict the efficacy of potential HIV-1 cure strategies, such as latency-reversing agents, early treatment initiation, or gene therapies, and to provide guidance for designing trials of these novel interventions.
| S-EPMC10612035 | biostudies-literature
Project description:Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV) drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP) is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no country has yet approved it for use with adolescents. The aim of this review was to identify and summarize the evidence from studies on PrEP for adolescents. We have compiled and reviewed published studies focusing on safety, feasibility, adherence to therapeutics, self-perception, and legal issues related to PrEP in people aged between 10 and 24 years.
| S-EPMC5716324 | biostudies-literature
Project description:The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.
| S-EPMC3143116 | biostudies-literature
Project description:BackgroundMultiple prevention measures have the possibility of impacting HIV incidence in South Korea, including early diagnosis, early treatment, and pre-exposure prophylaxis (PrEP). We investigated how each of these interventions could impact the local HIV epidemic, especially among men who have sex with men (MSM), who have become the major risk group in South Korea. A mathematical model was used to estimate the effects of each these interventions on the HIV epidemic in South Korea over the next 40 years, as compared to the current situation.MethodsWe constructed a mathematical model of HIV infection among MSM in South Korea, dividing the MSM population into seven groups, and simulated the effects of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination interventions on the incidence and prevalence of HIV infection, as compared to the current situation that would be expected without any new prevention measures.ResultsOverall, the model suggested that the most effective prevention measure would be PrEP. Even though PrEP effectiveness could be lessened by increased unsafe sex behavior, PrEP use was still more beneficial than the current situation. In the model, early diagnosis of HIV infection was also effectively decreased HIV incidence. However, early ART did not show considerable effectiveness. As expected, it would be most effective if all interventions (PrEP, early diagnosis and early treatment) were implemented together.ConclusionsThis model suggests that PrEP and early diagnosis could be a very effective way to reduce HIV incidence in South Korea among MSM.
| S-EPMC3963840 | biostudies-literature
Project description:Until now, decisions about how to allocate ART have largely been based on maximising the therapeutic benefit of ART for patients. Since the results of the HPTN 052 study showed efficacy of antiretroviral therapy (ART) in preventing HIV transmission, there has been increased interest in the benefits of ART not only as treatment, but also in prevention. Resources for expanding ART in the short term may be limited, so the question is how to generate the most prevention benefit from realistic potential increases in the availability of ART. Although not a formal systematic review, here we review different ways in which access to ART could be expanded by prioritising access to particular groups based on clinical or behavioural factors. For each group we consider (i) the clinical and epidemiological benefits, (ii) the potential feasibility, acceptability, and equity, and (iii) the affordability and cost-effectiveness of prioritising ART access for that group. In re-evaluating the allocation of ART in light of the new data about ART preventing transmission, the goal should be to create policies that maximise epidemiological and clinical benefit while still being feasible, affordable, acceptable, and equitable.
| S-EPMC3393661 | biostudies-other
Project description:ObjectiveDirect-acting antivirals have opened an opportunity for controlling hepatitis C virus (HCV) infection in Pakistan, where 10% of the global infection burden is found. We aimed to evaluate the implications of five treatment programme scenarios for HCV treatment as prevention (HCV-TasP) in Pakistan.DesignAn age-structured mathematical model was used to evaluate programme impact using epidemiological and programme indicators.SettingTotal Pakistan population.ParticipantsTotal Pakistan HCV-infected population.InterventionsHCV treatment programme scenarios from 2018 up to 2030.ResultsBy 2030 across the five HCV-TasP scenarios, 0.6-7.3 million treatments were administered, treatment coverage reached between 3.7% and 98.7%, prevalence of chronic infection reached 2.4%-0.03%, incidence reduction ranged between 41% and 99%, program-attributed reduction in incidence rate ranged between 7.2% and 98.5% and number of averted infections ranged between 126 221 and 750 547. Annual incidence rate reduction in the first decade of the programme was around 6%-18%. Number of treatments needed to prevent one new infection ranged between 4.7-9.8, at a drug cost of about US$900. Cost of the programme by 2030, in the most ambitious elimination scenario, reached US$708 million. Stipulated WHO target for 2030 cannot be accomplished without scaling up treatment to 490 000 per year, and maintaining it for a decade.ConclusionHCV-TasP is a highly impactful and potent approach to control Pakistan's HCV epidemic and achieve elimination by 2030.
| S-EPMC6537971 | biostudies-literature
Project description:The ongoing Antibody Mediated Prevention (AMP) trials will uncover whether passive infusion of the broadly neutralizing antibody (bNAb) VRC01 can protect against HIV acquisition. Previous statistical simulations indicate these trials may be partially protective. In that case, it will be crucial to identify the mechanism of breakthrough infections. To that end, we developed a mathematical modeling framework to simulate the AMP trials and infer the breakthrough mechanisms using measurable trial outcomes. This framework combines viral dynamics with antibody pharmacokinetics and pharmacodynamics, and will be generally applicable to forthcoming bNAb prevention trials. We fit our model to human viral load data (RV217). Then, we incorporated VRC01 neutralization using serum pharmacokinetics (HVTN 104) and in vitro pharmacodynamics (LANL CATNAP database). We systematically explored trial outcomes by reducing in vivo potency and varying the distribution of sensitivity to VRC01 in circulating strains. We found trial outcomes could be used in a clinical trial regression model (CTRM) to reveal whether partially protective trials were caused by large fractions of VRC01-resistant (IC50>50 μg/mL) circulating strains or rather a global reduction in VRC01 potency against all strains. The former mechanism suggests the need to enhance neutralizing antibody breadth; the latter suggests the need to enhance VRC01 delivery and/or in vivo binding. We will apply the clinical trial regression model to data from the completed trials to help optimize future approaches for passive delivery of anti-HIV neutralizing antibodies.
| S-EPMC7055956 | biostudies-literature
Project description:IntroductionModels that project the impact and cost-effectiveness of HIV pre-exposure prophylaxis (PrEP) must specify how PrEP use aligns with HIV exposure. We hypothesized that varying PrEP use according to individual-level partnership dynamics rather than prioritization to population subgroups based on average risk will result in larger incidence reductions and greater efficiency.MethodsWe used an individual-based network transmission model calibrated to HIV dynamics in Eswatini to simulate PrEP use among individuals ages 15-34 between 2022 and 2031 under two paradigms of PrEP delivery: "Risk Group" and "Partnership." In the "Risk Group" paradigm, we varied PrEP coverage by risk groups (low, medium and high) defined by average partnership frequency and concurrency. In the "Partnership" paradigm, all individuals are potentially eligible for PrEP, but we assumed use occurs only during partnerships and varied prioritization by partner HIV status (no prioritization to high prioritization with HIV-positive partners). We calculated person-time on PrEP and incidence relative to a no PrEP scenario and estimated efficiency as the person-years of PrEP needed to avert one additional infection (NNT).ResultsIn the Risk Group paradigm, restricting PrEP to the high-risk group was the most efficient (NNT = 17), but the number of infections averted was limited by the small size of the high-risk group. Expanding PrEP use to all risk groups averted up to three times more infections but with lower efficiency (NNT = 202). PrEP use under the Partnership paradigm was 2-6 times more efficient (NNT = 33-102) than the Risk Group paradigm with all groups eligible for PrEP. A 33% reduction in incidence among 15- to 34-year-olds was achieved at 46% (95% CI: 39-52%) PrEP coverage in the Risk Group paradigm and 6% (95% CI: 5-7%) to 17% (95% CI: 14-20%) in the Partnership paradigm.ConclusionsModelling PrEP use based on risk groups resulted in a sharp trade-off between PrEP efficiency and impact, whereas PrEP use predicated on partnerships resulted in much higher efficiency for widespread PrEP availability. Model estimates of PrEP impact and cost-effectiveness in generalized epidemics are strongly influenced by assumptions about how PrEP use aligns with individual-level HIV exposure heterogeneity.
| S-EPMC9670193 | biostudies-literature