Attitude towards antiretroviral pre-exposure prophylaxis (PrEP) prescription among HIV specialists

The impressive improvements in the treatability of HIV infection have not been paralleled by similarly remarkable improvements in the effectiveness of HIV prevention strategies; therefore, more successful approaches are urgently needed.

In the last years, the emphasis in the field of research on prevention has shifted to the development of combination prevention packages in which structural, behavioural, and biomedical interventions are implemented concurrently [1].

Biomedical prevention strategies include using antiretrovirals (ARV) treatment as prevention (TasP), i.e. treating HIV-infected patients, regardless of clinical status, to curb transmission. However, gaps in the continuum from HIV diagnosis, through linkage to care, uptake and adherence to antiretroviral therapy, are substantially limiting its actual impact [2, 3].

More recently, the use of ARV for pre-exposure prophylaxis (PrEP) among high-risk persons without HIV is emerging as one additional strategy to curtail the HIV epidemic.

While there have been significant studies suggesting the high potential efficacy of PrEP, although strongly related to adherence [4–7], others were halted early due to no difference between placebo and PrEP arms [8–10], again perhaps due to difficulties with adherence.

In any case, several questions arise about PrEP delivery in the real world. In particular, it seems necessary to understand the point of view of the providers on the actual implementation of PrEP in their clinical context, as well as to investigate how PrEP will be perceived by the communities of individuals at high risk.

In Italy, the care for HIV-infected patients, counseling, and testing were almost exclusively carried out by specialists in Infectious Diseases; the same is true for the provision of ARV. In addition, these HIV specialists have built up extensive expertise in prescribing ARV for post-exposure prophylaxis (PEP) to prevent occupational and sexual acquisition of HIV infection [11, 12].

Although PrEP has not been regulated or tested at a national level so far, HIV specialists are likely to be the first prescribers of PrEP [13], and might have patients who require it. We therefore decided to investigate perceptions regarding PrEP through a survey of HIV specialists, to assess their attitude to prescribe and monitor PrEP use, and to identify factors predictive of a positive attitude towards PrEP prescription.

The survey was conducted between February and May 2012, when the results of CAPRISA and iPREX trials had been published [4, 5], Partners and TDF2 studies had been presented [6, 7], and the inconsistent results of FEM-PrEP and VOICE studies were already available [8, 10].

In our survey, despite the multiple challenges identified, there was a prevalent positive attitude of HIV specialists towards PrEP prescription. Indeed, 70% of respondents would offer PrEP, mainly to serodiscordant partners (64%), especially women and MSM engaged with viraemic partners, but also (56%) to people at ongoing, high risk of HIV infection, primarily MSM, persons with STI and sex workers not using condoms.

This correlates with the current epidemic pattern in Italy, where some 4000–10000 (according to the different models and data sources) new HIV infections are estimated to occur yearly: the highest estimated number of recent infections is among MSM [17, 18], and the highest HIV prevalences have been observed in MSM, persons with a current STI, and sex workers [19].

Regardless of their attitude, respondents expressed the concern that widespread access to PrEP could lead to an increased incidence of HIV and STI among at-risk populations, unintended toxicity and the emergence of resistant strains, consistently with other studies [13, 15, 20]. However, only toxicity concerns were significantly more frequent among specialists showing a negative attitude towards PrEP. As for financial sustainability, although deemed too expensive, most specialists advocated NHS support of PrEP costs to ensure equity of access, consistently with other studies where healthcare providers recognized cost as a major barrier for patients [13], and wished public programmes to pay for PrEP if patients cannot afford it [15].

Currently, PrEP is considered cost-effective when targeted to high-risk populations with an annual incidence >2% [21], as evidenced for MSM in Italy [22]; further targeting based on risk factors (younger age, number of annual partners, not being tested for HIV annually) could help reducing PrEP financial impact.

The main predictor of a negative attitude towards PrEP prescription seems to be the scarce propensity to offer or inform patients on PEP, and more in general to consider ARV as a tool to prevent HIV transmission. Specialists with a negative attitude believe behavioural interventions to be more effective than PrEP, and feel uncomfortable when prescribing drugs for new indications unless there is clear evidence of benefit. The results of a survey conducted at the conclusion of the 2012 International Association of Physicians in AIDS Care (IAPAC) meeting “Controlling the HIV Epidemic with Antiretrovirals” are in line with ours: over half of the summit attendees (56%) chose funding as the largest barrier to implementation of PrEP; most participants (70%) said that in their country PrEP will be used only in selected cases, and mostly (91%) following formal PrEP guidelines [23].

Even in our study most HIV specialists would welcome guidelines on PrEP, and the start of a clinical trial where their patients could be enrolled. Those with a negative attitude did not consider advisable that formal PrEP guidelines were issued (OR 0.30; 95% CI 0.13-0.66; p = 0.003).

When our survey was conducted only two guidance documents were available, from the Centers for Disease Control and Prevention (CDC) [24] and the British HIV Association/British Association for Sexual Health and HIV [25], mainly oriented to limit inappropriate prescription, respectively, among MSM and outside the context of a clinical research study.

Following FDA approval [26], and the availability of conclusive data from studies of oral PrEP among heterosexuals [6, 7], the WHO released recommendations [27], and the CDC issued a second interim guidelines targeted to high-risk heterosexually active adults [28], both aimed at guiding clinicians on providing PrEP outside of the context of controlled clinical trials. So far, the European Medicines Agency (EMA) has issued a Reflection paper whose purpose is to highlight regulatory aspects regarding the preclinical and clinical development of PrEP [29].

Whether and how these documents might impact on HIV specialists’ attitude and concerns and on the European and Italian settings, will need monitoring and further reassessment.

Some of the barriers to PrEP prescription evidenced in our study will probably be addressed by future trials and open label studies [30].

Other concerns, such as adherence, risk disinhibition and the emergence of resistant strains, need further evidence on wider populations and longer periods of observation.

It is encouraging that HIV specialists, already loaded with their current activities, strongly disagree with a lack of time to engage in prevention counselling and clinical monitoring of individuals on PrEP, differently from what observed in other studies [20]. This is somehow consistent with the high frequency with which PEP information and treatment is provided in this group, and in accordance with similar observations both in HIV specialists and in generalists [15].

Training and providing continuing education to the health workforce is another significant challenge. In our survey, one third of interviewed HIV specialists reported a poor knowledge of PrEP; also during the focus group, participants reported unsatisfactory knowledge of PrEP trial results. Even if we did not find a significant association with the reported attitude towards PrEP prescription, better knowledge has been associated with a higher willingness to prescribe PrEP [13, 15].

Our results may not apply to the whole population of Italian HIV specialists.

First of all the participation rate was weak (40%), and no data have been collected allowing to compare anonymous respondents with non-respondents in order to characterize the possible participation bias. Participants represent a convenience sample, obtained using two different recruitment methods (i.e. participation in HIV educational courses versus participation in the online survey). The online sample is composed only of members of the Italian Society of Infectious Diseases, which collects most, but not all, of the Italian infectious disease/HIV specialists.

Social desirability bias may have influenced the answers to the questionnaires provided at the educational HIV courses, although anonymous. This could explain at least in part the significantly more positive attitude towards PrEP prescription among respondent specialists who participated in the HIV courses.

Conversely, previous studies have demonstrated that online data collection has the potential to limit this bias and result in more honest and accurate responses [31, 32].

Therefore, we performed a sub-analysis only of the online sample: the results we obtained were consistent with those of the overall population.

Moreover, the questionnaire did not collect any personal information about the physician (e.g. marital status, being HIV positive or having close friends at risk of or with HIV infection, religious faith or political beliefs, etc.) which could influence specialists’ attitude toward PrEP in higher proportions than the professional characteristics tested in the model [33, 34]; indeed, the multivariate model only explains 17.2% of the variance. Therefore, further studies are needed to identify other predictors of PrEP prescription apart from PEP provision.

In conclusion, the majority of respondent HIV specialists would prescribe PrEP in specific situations. However, conflicting attitudes appear evident, in line with the results of a New England Journal of Medicine polling on PrEP, and reflect uncertainties within the medical and public health communities over which approaches will most effectively control the global spread of HIV [35]. Whether additional scientific evidence and enhanced knowledge could modify attitudes needs monitoring and further investigation.

Identifying the populations at high risk for HIV infection and for whom PrEP use would be most effective, and linking and retaining them in care, is one of the emerging challenges. HIV specialists seem to be willing, pending further evidence from ongoing studies and guidance from normative bodies, to promote PrEP within multiple prevention strategies among vulnerable populations.