ARTÍCULO DE OPINIÓN

 

Pre-exposure prophylaxis for the prevention of HIV infection: a new prevention paradigm?

Profilaxis preexposición al VIH: ¿un nuevo paradigma de prevención?

 

 

Javier Sánchez-Rubio Ferrández¹ and José Manuel Martínez Sesmero²

¹Hospital Universitario de Getafe, Madrid.
²Hospital Virgen de La Salud, Toledo. Spain.

Correspondence

 

 

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ABSTRACT

Pre-exposure prophylaxis" (PrEP) has been recently developed as a prevention strategy which involves the administration of drugs to non-infected individuals who present high exposure or susceptibility to HIV. Although this use is not approved in our country, several guidelines recommend PrEP as a prevention option in adult MSM, heterosexual men and women, and users of parenteral drugs at risk of acquiring the infection. This article presents the characteristics that an ideal agent to be used as PrEP should meet, recent efficacy published data and barriers for the implementation of this new strategy. On the other hand, the role of hospital pharmacists will be discussed.

Key words: HIV; Pre-exposure prophylaxis; Prevention.

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RESUMEN

La "profilaxis pre-exposición (PrEP)" ha sido recientemente desarrollada como una estrategia de prevención que consiste en la administración de medicamentos a los individuos no infectados que presentan una alta exposición y susceptibilidad al VIH. Aunque este uso no está aprobado en nuestro país, varias guías recomiendan la PrEP como una opción de prevención en HSH adultos, hombres y mujeres heterosexuales, y los usuarios de drogas parenterales en riesgo de adquirir la infección. Este artículo presenta las características que un agente ideal para ser utilizado como profilaxis pre-exposición debe cumplir, los datos de eficacia recientemente publicados y las barreras para la implementación de esta nueva estrategia. Por otra parte, se discute el papel de los farmacéuticos del hospital en la posible implantación de esta estrategia en el futuro.

Palabras clave: VIH; Profilaxis pre-exposición; Prevención.

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The Human Immunodeficiency Virus (HIV) infection still represents a major health problem in our country, from the healthcare, social, economic and human points of view.

The development of high-activity antiretroviral treatment has contributed to a high extent to the control and chronification of the disease, and better clinical outcomes are increasingly achieved. However, these treatments are not free of problems such as the adverse effects caused, difficulties in treatment compliance, interactions, development of resistance, the difficulty to reconcile them with the comorbidities that patients might suffer along their lives, and their associated cost.

According to data available in 2013, it is estimated that in Spain there are 10.3 new diagnoses of infection per 100,000 inhabitants every year. This rate has remained stable during the 5 years previous to the analysis mentioned, though a change in trend is observed depending on type of transmission: it has reduced or become stable in parenteral drug users and heterosexual patients, and it is increasing among men who have sex with men (MSM), particularly in the 25-to-34-year-old group¹. For this reason, it has become necessary to strengthen the multidisciplinary prevention policies which will allow to reduce the propagation of this disease.

The so-called "pre-exposure prophylaxis" (PrEP) has been recently developed as a prevention strategy in the HIV setting. This involves the administration of drugs to non-infected individuals who present high exposure or susceptibility to this pathogen.

Although this indication has not been approved for antiretroviral therapy in our country, the studies conducted so far led to the authorization by the FDA in 2012 of this use in the case of the tenofovir-emtricitabine combination. The American Center for Disease Control and Prevention (CDC) recommends PrEP as a prevention option in adult MSM, heterosexual men and women, and users of parenteral drugs at risk of acquiring the infection. On the other hand, it is considered as a possible option to be discussed with serodiscordant couples². Moreover, the World Health Organization (WHO) has also included the use of PrEP in its recommendations for prevention in MSM and serodiscordant couples³.

Some of the characteristics that an ideal agent to be used as PrEP should meet are: safety in chronic and intermittent use in different populations, good penetration in target tissues, activity against HIV, prolonged effect which allows an acceptable dosing regimen, high genetic barrier against the development of resistance, low interaction potential, if possible not being part of any existing treatment regimen, ease of use, and low economic impact⁴.

During the last decade, different methods of this strategy have been tried in different populations at risk. Firstly, the efficacy of the use of topical tenofovir with vaginal gel formulation at 1% has been tested for PrEP. This way of administration presents the theoretical advantages of higher drug concentration in the target tissue with lower systemic exposure, and therefore lower toxicity. However, despite the positive outcomes of the CAPRISA004⁵ clinical trial, two subsequent studies have failed to demonstrate the efficacy of this gel in the reduction of the transmission rate^6,7.

For this reason, the efforts for PrEP development have been turned towards the use of new formulations such as vaginal rings and anal gels, as well as systemic agents. In this sense, various studies have assessed the efficacy of the oral administration of tenofovir, alone or typically in combination with emtricitabine, as a continuous or intermittent therapy, and their outcomes have been inconsistent. Thus, the iPREX, TDF2, Partners PrEPP, Bangkok, PROUD and Ipergay studies obtained a reduction in transmission rates that could not be confirmed in the FEM-PrEP and VOICE⁸ trials, as shown in table 1.

A detailed analysis of the studies points at lack of compliance as the main cause for the differences in outcomes found. Thus, PrEP becomes a highly effective strategy when patients reach high compliance rates, particularly among MSM; therefore, compliance of the prescribed dosing is the weak link of PrEP as a prevention strategy. The development of prolonged-release injectable agents can help to improve this aspect in future studies⁹.

Other aspects which still generate doubts about the wide implementation of this strategy is its potential impact on the profiles of risky sexual behaviours (risk compensation), as well as on the contagion of sexually transmitted infections other than HIV. In this sense, and even though there are still limited data, studies have not shown that the application of PrEP will worsen any of these aspects in a statistically significant manner⁸. However, it must be taken into account that the study conditions might not reflect usual practice and that in all studies the pharmacological therapy was reinforced with educational and behaviour strategies for patients, as well as free supply of condoms. This aspect strengthens the importance of approaching prevention from different points of view, so that the application of a certain strategy should not imply a relaxation in the others, but become a complementary weapon in the fight against transmission.

On the other hand, the individuals receiving these medications can be exposed to their adverse effects, still not well evaluated at long term, in the same way as patients who are taking them for disease treatment. And given that this is an antiretroviral treatment, resistance can be developed by using sub-optimal therapies in those patients who might have an unnoticed infection and initiate a PrREP regimen. Therefore, the selection of those patients who must receive this treatment, and their follow-up over time, will be another aspect required in this type of strategy.

Finally, we must not forget that the drugs used for PrEP are expensive, and that extending this strategy to all the population at risk might represent a major investment of resources, at a time in which these have become very limited. However, as with any other healthcare technology, the cost-efficacy of PrEP should be closely analyzed, because the cost of each prevented infection should not be disregarded, and even more if we take into account the chronic nature of the treatment that any new infected individual would currently receive. On the other hand, and from a social perspective, an exponential increase in new infections could be prevented, leading to a reduction of other type of associated costs. All this opens the discussion about reimbursement, which will undoubtedly require an adequate critical assessment of the evidence available, and the therapeutic positioning of this strategy from the perspective of the National Health Systems.

In order to clarify these controversies, we believe that the Hospital Pharmacy must undoubtedly play a major role in the discussion of PrEP implementation, which will surely be conducted within the next years; and, as in other occasions, they will need to face the challenge of a new therapeutic paradigm. On one hand, they will be involved in the preparation of protocols and guidelines which allow to determine the criteria for selecting patients who may benefit from this new method, guaranteeing its efficacy. On the other hand, as already occurs in HIV treatment, the role of the Pharmacist in terms of follow-up will be key to maintain the efficacy of these drugs by monitoring compliance, detecting and managing any potential adverse effects, providing specialized advice, and implementing educational programs in order to ensure an adequate knowledge of treatments and to prevent a shift towards other risky behaviours.

 

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Correspondence:
Correo electrónico: javier.sanchez@salud.madrid.org
(Javier Sánchez-Rubio Ferrández).

Recibido el 24 de diciembre de 2015;
aceptado el 4 de febrero de 2016.