The art of HIV elimination: past and present science

Introduction: Remarkable strides have been made in controlling the HIV epidemic, although not enough to achieve epidemic control. More recently, interest in biomedical HIV control approaches has increased, but substantial challenges with the HIV cascade of care hinder successful implementation. We summarise all available HIV prevention methods and make recommendations on how to address current challenges. Discussion: In the early days of the epidemic, behavioural approaches to control the HIV dominated, and the few available evidence-based interventions demonstrated to reduce HIV transmission were applied independently from one another. More recently, it has become clear that combination prevention strategies targeted to high transmission geographies and people at most risk of infections are required to achieve epidemic control. Biomedical strategies such as male medical circumcision and antiretroviral therapy for treatment in HIV-positive individuals and as preexposure prophylaxis in HIV-negative individuals provide immense promise for the future of HIV control. In resourcerich settings, the threat of HIV treatment optimism resulting in increased sexual risk taking has been observed and there are concerns that as ART roll-out matures in resource-poor settings and the benefits of ART become clearly visible, behavioural disinhibition may also become a challenge in those settings. Unfortunately, an efficacious vaccine, a strategy which could potentially halt the HIV epidemic, remains elusive. Conclusion: Combination HIV prevention offers a logical approach to HIV control, although what and how the available options should be combined is contextual. Therefore, knowledge of the local or national drivers of HIV infection is paramount. Problems with the HIV care continuum remain of concern, hindering progress towards the UNAIDS target of 90-90-90 by 2020. Research is needed on combination interventions that address all the steps of the cascade as the steps are not independent of each other. Until these issues are addressed, HIV elimination may remain an unattainable goal

Proven HIV Prevention Strategies

Describes strategies that, used in combination, have proven to be effective in preventing sexual, blood-borne, and mother-to-child transmission of HIV. Discusses promising methods and structural interventions to reduce the vulnerability of those at risk

PrEP as a feature in the optimal landscape of combination HIV prevention in sub-Saharan Africa

INTRODUCTION: The new WHO guidelines recommend offering pre-exposure prophylaxis (PrEP) to people who are at substantial risk of HIV infection. However, where PrEP should be prioritised, and for which population groups, remains an open question. The HIV landscape in sub-Saharan Africa features limited prevention resources, multiple options for achieving cost saving, and epidemic heterogeneity. This paper examines what role PrEP should play in optimal prevention in this complex and dynamic landscape. METHODS: We use a model that was previously developed to capture subnational HIV transmission in sub-Saharan Africa. With this model, we can consider how prevention funds could be distributed across and within countries throughout sub-Saharan Africa to enable optimal HIV prevention (that is, avert the greatest number of infections for the lowest cost). Here, we focus on PrEP to elucidate where, and to whom, it would optimally be offered in portfolios of interventions (alongside voluntary medical male circumcision, treatment as prevention, and behaviour change communication). Over a range of continental expenditure levels, we use our model to explore prevention patterns that incorporate PrEP, exclude PrEP, or implement PrEP according to a fixed incidence threshold. RESULTS: At low-to-moderate levels of total prevention expenditure, we find that the optimal intervention portfolios would include PrEP in only a few regions and primarily for female sex workers (FSW). Prioritisation of PrEP would expand with increasing total expenditure, such that the optimal prevention portfolios would offer PrEP in more subnational regions and increasingly for men who have sex with men (MSM) and the lower incidence general population. The marginal benefit of including PrEP among the available interventions increases with overall expenditure by up to 14% (relative to excluding PrEP). The minimum baseline incidence for the optimal offer of PrEP declines for all population groups as expenditure increases. We find that using a fixed incidence benchmark to guide PrEP decisions would incur considerable losses in impact (up to 7%) compared with an approach that uses PrEP more flexibly in light of prevailing budget conditions. CONCLUSIONS: Our findings suggest that, for an optimal distribution of prevention resources, choices of whether to implement PrEP in subnational regions should depend on the scope for impact of other possible interventions, local incidence in population groups, and total resources available. If prevention funding were to become restricted in the future, it may be suboptimal to use PrEP according to a fixed incidence benchmark, and other prevention modalities may be more cost-effective. In contrast, expansions in funding could permit PrEP to be used to its full potential in epidemiologically driven prevention portfolios and thereby enable a more cost-effective HIV response across Africa

Averting HIV Infections in New York City: A Modeling Approach Estimating the Future Impact of Additional Behavioral and Biomedical HIV Prevention Strategies

Background:New York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically.Methods:A new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling team and the NYC Department of Health and Mental Hygiene. The model projects the impact of different prevention strategies, or portfolios of prevention strategies, on the HIV epidemic in NYC.Results:Ten unique interventions were able to provide a prevention benefit at an annual program cost of less than $360,000, the threshold for consideration as a cost-saving intervention (because of offsets by future HIV treatment costs averted). An optimized portfolio of these specific interventions could result in up to a 34$106,378; the total cost was in excess of $2 billion (over the 20 year period, or approximately$100 million per year, on average). The cost-savings of prevented infections was estimated at more than $5 billion (or approximately$250 million per year, on average).Conclusions:Optimal implementation of a portfolio of evidence-based interventions can have a substantial, favorable impact on the ongoing HIV epidemic in NYC and provide future cost-saving despite significant initial costs. © 2013 Kessler et al

Contributions to the Mathematical Systems Medicine of Antimicrobial Therapy and Genotype-Phenotype Inference.

The following summary of my publications describes the main ideas in the corresponding research articles and clarfifies my contribution in multi-author publications. I decided to apply for habilitation according to x2.I.1.(c) of the Habilitationsordnung (this path is usually referred as Kumulative Habilitation"). I selected 13 first- or last author publications for this habilitation that concern contributions to the mathematical systems medicine of antiviral therapy [tMH10, tMS+11, FtK+11, tMMS12, DSt12, DWSt15, Dt16, DSt16, DDKt18, DSD+19, DDKt19], as well as inference of genotype-phenotype associations [SDH+15, SSJ+18]. The selected publications represent my major contributions in this research eld since submitting my doctoral thesis in September 2009

HIV/AIDS Study. Bibliographic review of the virus and mathematical models.

The human immunodeficiency virus is a global pandemic that causes thousands of deaths a year. It is caused by two lentivirus that can already either type 1 or 2 (HIV-1, HIV-2) and are spread by blood or bodily fluids. HIV infection has an incubation period of 8 to 10 years and is characterized by attacking CD4 cells in the immune system. Today, the World Health Organization (WHO) estimates that more than 37 million people live with HIV worldwide, of which only half have access to antiretroviral therapy. The main function of the therapy is to reduce the rate at which HIV replicates in the body by using combinations of drugs. Nowadays, the HIV virus continues to have a major impact on the world due to its rapid spread and the significant number of cases in certain areas, specifically sub-Saharan Africa. While in most countries the growth rate tends to fall, in the case of sub-Saharan Africa it is still growing. The use of HIV treatments and vaccines have helped in the non-development of the virus, yet the problem still remains. That is why other tools have been used in recent years to prevent and analyze the problem of the epidemic, such as the use of mathematical models. These can help us understand the evolution of HIV in the world as is the HIV clinical course. In this work, a bibliographic review of the current knowledge about HIV is proposed, as well as the mathematical models that have been used in its study. This work is the starting point of a new line of research of the Computational Biology and Complex Systems Group of the Polytechnical University of Catalonia.El virus de la inmunodeficiencia humana es una pandemia a nivel mundial que causa miles de muertes al año. Esta causada por dos lentivirus, ya pueden ser del tipo 1 o 2 (VIH-1, VIH-2) y se contagia mediante la sangre o fluidos corporales. La infección por VIH tiene un periodo de incubación de 8 a 10 años y se caracteriza por atacar a las células CD4 del sistema inmunitario. Hoy en día, la Organización Mundial de la Salud (OMS) calcula que más de 37 millones de personas viven con el VIH en todo el mundo. De los cuales, solo la mitad tiene acceso a la terapia antirretroviral. La función principal de la terapia es reducir la velocidad a la que el VIH hace copias de sí mismo en el organismo mediante el uso de combinaciones de medicamentos. Hoy en día, el virus del VIH sigue teniendo una gran repercusión en el mundo debido a su rápida propagación y a la notable cantidad de casos en ciertas zonas como es el caso del África Subsahariana. Mientras en la mayoría de los países el índice de crecimiento tiende a bajar, en el caso de África subsahariana sigue en crecimiento. El uso de tratamientos y vacunas para el VIH han ayudado al no desarrollo del virus, aun así, el problema sigue vigente. Es por ello, que en los últimos años se han usado otras herramientas para prevenir y analizar el problema de la epidemia, como es el caso del uso de modelos matemáticos. Estos, nos pueden hacer entender la evolución del VIH en el mundo como es también el curso clínico del VIH. En este trabajo se plantea una revisión bibliográfica del conocimiento actual sobre el VIH, así como de los modelos matemáticos que se han utilizado en su estudio. Este trabajo es el punto de partida de una nueva línea de investigación del Grupo de Biología Computacional i Sistemas Complejos de la Universidad Politécnica de Cataluña.El virus d'Immunodeficiència humana és una pandèmia global que provoca milers de morts a l'any. És causada per dos lentivirus, poden ser tipus 1 o 2 (VIH-1, HIV-2) i es propaga per sang o fluids corporals. La infecció pel VIH té un període d'incubació de 8 a 10 anys i es caracteritza per atacar a les cèl·lules de CD4 en el sistema immunitari. Avui en dia, l'organització mundial de la salut (OMS) estima que més de 37 milions de persones viuen amb el VIH a tot el món, de les quals només la meitat tenen accés a la teràpia antiretroviral. La funció principal de la teràpia és reduir la velocitat a la qual el VIH fa còpies de si mateix en el cos mitjançant l'ús de combinacions de fàrmacs. Avui en dia, el virus del VIH continua tenint un impacte important en el món a causa de la seva ràpida propagació i el nombre significatiu de casos en certes àrees com l'Àfrica subsahariana. Mentre que en la majoria dels països la taxa de creixement tendeix a disminuir, en el cas de l'Àfrica subsahariana, encara està en creixement. L'ús dels tractaments del VIH i les vacunes han ajudat al no-desenvolupament del virus, però, el problema es manté. És per això que s'han utilitzat altres eines en els últims anys per prevenir i analitzar el problema de l'epidèmia, com ara l'ús de models matemàtics. Aquests ens poden fer entendre l'evolució del VIH al món com també el curs clínic del VIH. En aquest treball es planteja una revisió bibliogràfica del coneixement actual sobre el VIH, així com dels models matemàtics que s'han utilitzat en el seu estudi. Aquest treball és el punt de partida d'una nova línia de recerca del Grup de Biologia Computacional i Sistemes Complexos de la Universitat Politècnica de Catalunya

Viral dynamics of acute HIV-1 infection.

Viral dynamics were intensively investigated in eight patients with acute HIV infection to define the earliest rates of change in plasma HIV RNA before and after the start of antiretroviral therapy. We report the first estimates of the basic reproductive number (R(0)), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted. The mean initial viral doubling time was 10 h, and the peak of viremia occurred 21 d after reported HIV exposure. The spontaneous rate of decline (alpha) was highly variable among individuals. The phase 1 viral decay rate (delta(I) = 0.3/day) in subjects initiating potent antiretroviral therapy during acute HIV infection was similar to estimates from treated subjects with chronic HIV infection. The doubling time in two subjects who discontinued antiretroviral therapy was almost five times slower than during acute infection. The mean basic reproductive number (R(0)) of 19.3 during the logarithmic growth phase of primary HIV infection suggested that a vaccine or postexposure prophylaxis of at least 95% efficacy would be needed to extinguish productive viral infection in the absence of drug resistance or viral latency. These measurements provide a basis for comparison of vaccine and other strategies and support the validity of the simian immunodeficiency virus macaque model of acute HIV infection

HIV treatment as prevention : models, data, and questions-towards evidence-based decision-making

Antiretroviral therapy (ART) for those infected with HIV can prevent onward transmission of infection, but biological efficacy alone is not enough to guide policy decisions about the role of ART in reducing HIV incidence. Epidemiology, economics, demography, statistics, biology, and mathematical modelling will be central in framing key decisions in the optimal use of ART. PLoS Medicine, with the HIV Modelling Consortium, has commissioned a set of articles that examine different aspects of HIV treatment as prevention with a forward-looking research agenda. Interlocking themes across these articles are discussed in this introduction. We hope that this article, and others in the collection, will provide a foundation upon which greater collaborations between disciplines will be formed, and will afford deeper insights into the key factors involved, to help strengthen the support for evidence-based decision-making in HIV prevention

Comparing the impact of increasing condom use or HIV pre-exposure prophylaxis (PrEP) use among female sex workers.

In many settings, interventions targeting female sex workers (FSWs) could significantly reduce the overall transmission of HIV. To understand the role HIV pre-exposure prophylaxis (PrEP) could play in controlling HIV transmission amongst FSWs, it is important to understand how its impact compares with scaling-up condom use-one of the proven HIV prevention strategies for FSWs. It is important to remember that condoms also have other benefits such as reducing the incidence of sexually transmitted infections and preventing pregnancy. A dynamic deterministic model of HIV transmission amongst FSWs, their clients and other male partners (termed 'pimps') was used to compare the protection provided by PrEP for HIV-negative FSWs with FSWs increasing their condom use with clients and/or pimps. For different HIV prevalence scenarios, levels of pimp interaction, and baseline condom use, we estimated the coverage of PrEP that gives the same reduction in endemic FSW HIV prevalence or HIV infections averted as different increases in condom use. To achieve the same impact on FSW HIV prevalence as increasing condom use by 1%, the coverage of PrEP has to increase by >2%. The relative impact of PrEP increases for scenarios where pimps contribute to HIV transmission, but not greatly, and decreases with higher baseline condom use. In terms of HIV infections averted over 10 years, the relative impact of PrEP compared to condoms was reduced, with a >3% increase in PrEP coverage achieving the same impact as a 1% increase in condom use. Condom promotion interventions should remain the mainstay HIV prevention strategy for FSWs, with PrEP only being implemented once condom interventions have been maximised or to fill prevention gaps where condoms cannot be used