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Abstract

Early use of highly active antiretroviral treatment (ART) in people living with HIV for HIV prevention has gained legitimacy but remains controversial. Nineteen French HIV experts with diverse specializations (over half of whom were clinicians) were qualitatively interviewed on their views about ART irrespective of CD4 count of more than 500 cells/mm³ for purposes of HIV prevention, which is not systematically recommended in France. Content analysis identified 2 broad categories: individual considerations (subcategories: patient health and well-being; patient preparedness and choice) and collective considerations (subcategories: HIV transmission risk; impact on the epidemic; cost). Uncertainty surrounded many experts’ considerations, and unity was lacking on key issues (eg, candidacy for early preventive treatment, expected clinical- and population-level effects). An umbrella theme labeled “Weighing the merits of early ART in the face of uncertainties” was identified. Our analyses raise doubts about the current acceptability of widespread implementation of early ART for HIV prevention in France.

Keywords

antiretroviral treatment treatment as prevention uncertainty qualitative methods France

Introduction

Early use of highly active antiretroviral treatment (ART) in people living with HIV for HIV prevention has gained legitimacy, and updated treatment guidelines in some resource-rich settings reflect this.^1
–3 According to many mathematical models, maximizing the public health impact of treatment as prevention (TasP) requires treating with ART all or virtually all individuals diagnosed with HIV.^4
–6 This prospect, however, raises many concerns (eg, ethical, financial, and behavioral)⁷ and is at odds with medical guidelines that largely rely on CD4 counts to determine when to initiate ART.⁸ Deciding “when to start” ART remains an important unresolved issue in HIV treatment, and no randomized clinical trial data are yet available on the clinical benefit of treatment when CD4 counts exceed 500 cells/mm³.⁹

In France, 2009 to 2010 saw the publication of multiple official reports indicating a paradigm shift in HIV prevention, with a novel focus on HIV prevention and the integration of TasP.¹⁰ These include a report by the French National AIDS Council on the role of treatment in fighting the HIV epidemic,¹¹ a report on prevention and risk reduction in high-risk groups against HIV and sexually transmitted infection (STI),¹² the 2010 French guidelines for the medical care of people with HIV,¹³ and the national plan for fighting HIV/AIDS-STI, which, for the first time, adopted a combination prevention strategy of behavioral prevention, expanded HIV testing, and earlier ART, as recommended by the former reports.¹⁴ To some extent, because of its strong emphasis on HIV testing and treatment, France is considered a setting where a natural experiment with TasP has taken place.¹⁵ However, TasP has been the object of controversy in France,¹⁶ and the country’s HIV medical guidelines are more cautious toward it¹⁷ than those in the United States, for example.² Among asymptomatic patients, ART is recommended for those with a CD4 count between 350 and 500 cells/mm³ and, among those with more than 500 cells/mm³, the clinician’s decision to begin ART can take account of the objective of reducing the risk of sexual HIV transmission.¹³ Treatment of patients with a CD4 count of more than 500 cells/mm³ is thus not systematically recommended. The government’s 2010 to 2014 national plan for HIV/AIDS-STI does propose to study the possibility of immediately and continuously treating newly diagnosed HIV-positive persons with ART.¹⁴

In a context of growing international interest in TasP, this study’s objective was to analyze French HIV experts’ main considerations in regard to early ART for HIV prevention to better ascertain the feasibility of its broader implementation. This study adds to current research premised on the notion that a better understanding of stakeholders’ attitudes toward early ART is essential to this project.^18
–20

Methods

Participants

Diverse HIV experts were recruited to participate in a qualitative study aimed at understanding whether and how a “test and treat” strategy should be implemented in France. A sample of 19 HIV experts participated (5 women and 14 men). Expertise was defined on the basis of either contributing as an expert to the latest French recommendations for the medical care of HIV-infected persons¹³ (n = 15) or being referred as a good candidate for the study by one of these experts (n = 4). Experts had worked in the HIV field for a mean of 24.6 years (standard deviation = 5.1 years). Most (16) currently worked in Paris and over half (11) were practicing clinicians. Other occupations represented include virologist (4), AIDS service organization worker (2), and researcher (3). Table 1 provides additional information on the participants. Given the sample’s high-profile membership, to protect the experts’ identities, citations provided here are accompanied by minimal information on their producers.

Table 1.

Characteristics of the Sample of French HIV Experts.^a

N = 19	Main Occupation(s)	Years in HIV	Main Specialization(s) in HIV	Institution(s) Where Expert Works	City
1	Medical doctor (clinician)	25	Medical treatment and care	University hospital	Paris
	Head of public health unit		Organization of health care	French National AIDS Council
	Vice president, French National AIDS Council		Public policy
2	Virologist	18	Virology (impact of ART on genital and intestinal reservoirs; mucosal interactions and HIV)	University hospital	Saint- Etienne
2	Assistant professor	18		University	Saint- Etienne
3	Medical doctor	19	Virology	University hospital	Paris
	Virologist			University
	Professor
4	Medical doctor (clinician)	25	Medical treatment and care	Hospital	Paris
				Private clinic
5	Research director	26	Biostatistical methods	French National Institute of Health and Medical Research	Paris
			Epidemiology
			Effects of ART
			Resistance to ART
			Severe morbidity
			Clinical trials
			Mathematical modeling
6	Medical doctor (clinician)	18	Medical treatment and care	University hospital	Nice
7	Medical doctor (clinician)	29	Medical treatment and care	University hospital	Nice
	Professor		HIV genotyping for adapted therapy	University
			Trans-placental diffusion of ART
8	Medical doctor (clinician)	30	Immunology	University hospital	Paris
	Director of the French National Agency of AIDS and Viral Hepatitis Research		Internal medicine	French National Agency of AIDS and Viral Hepatitis Research
	Professor			University
9	Coordinator of HIV prevention, ASO	23	Social rights	AIDS service organization	Paris
	Advocate for HIV-positive persons and health care users		ART and research
	Advocate for HIV-positive persons and health care users		HIV prevention
10	Medical doctor (clinician)	30	ART treatment strategies	University hospital	Paris
	Professor			University
11	Researcher	25	Social sciences	French National Institute of Health and Medical Research	Paris
			Epidemiology
			(HIV prevention, prevention and care with drug users, HIV transmission risk in health care workers, palliative care, life conditions and chronic HIV infection, and HIV testing)
12	Medical doctor	15	Virology and resistance to ART	University hospital	Paris
	Virologist			University
	Assistant professor
13	Medical doctor (clinician)	25	Medical treatment and care	University hospital	Paris
	Professor		HIV prevention	French National Agency for AIDS and Viral Hepatitis Research
14	Medical doctor	22	Resistance to ART	University hospital	Paris
	Virologist		Viral reservoirs	University
	Professor		Epidemiology
			Clinical trials
15	Medical doctor (clinician)	29	HIV vaccine	University hospital	Paris
	Head of infectious and tropical diseases unit		Hepatitis C or B coinfection Preexposure prophylaxis	University
	Professor		HIV prevention tools
16	Medical doctor (clinician)	31	Medical treatment and care	University hospital	Paris
	Professor			University
17	President of AIDS service organization	29	Public health	AIDS service organization	Paris
	Researcher		Social sciences and humanities	French National Institute of Health and Medical Research	Marseille
18	Medical doctor (clinician)	18	Medical treatment and care	University hospital	Paris
			HIV testing and prevention Epidemiology Economics	French National Institute of Health and Medical Research
19	Medical doctor (clinician)	31	Medical treatment and care	University Hospital	Paris
	President of French National AIDS Council		Immunology	French National AIDS Council University
	Professor

Abbreviations: ART, antiretroviral therapy; ASO, AIDS service organization.

^aReprinted from Lebouché B, Engler K, Lévy JJ et al⁴⁹ with permission from Taylor & Francis Ltd. (www.tandfonline.com).

The Interview

Interviews, led by Bertrand Lebouché in French, were conducted from February to July 2011, following a semistructured format. They examined experts’ opinion of test and treat, how testing and treatment should proceed in this context, and barriers to its implementation. Interviews lasted, on average, for 64 minutes and were audio recorded. Interviewees provided written consent, following an explanation of the study and of what participation entailed.

Ethics Approval

Ethics approval for the study was obtained from a Research Ethics Board of the McGill University Health Centre, Montreal, Quebec, and in Lyon, France, from the Comité de Protection des Personnes of Hôtel-Dieu hospital.

Qualitative Analysis

The audio recorded interviews were transcribed verbatim, entered into the software Atlas-ti (5.2), and analyzed with content analysis.²¹ The interview material was initially divided into 20 broad and minimally interpreted content areas²² with Atlas.ti. The content area pertaining to the decision to treat people living with HIV early with ART for prevention was analyzed for this article. Analysis of this content produced a hierarchy of categories (2), subcategories (5), and codes (16), which were fine-tuned and continuously verified against the original transcripts. An underlying theme was found to cut across these constructs.²² The analyses and their component interview excerpts were discussed and agreed upon by the research team. The person responsible for analysis (Kim Engler) had minimal information on the interview participants and was not present at the interviews.

Results

On the decision to treat people living with HIV early for prevention, experts’ main considerations could be grouped into 2 broad categories: considering the individual (subcategories: patient health and well-being; patient preparedness and choice), illustrated in Table 2, and considering the collective (subcategories: HIV transmission risk; impact on the epidemic; cost), illustrated in Table 3.

Table 2.

Experts’ Individual Considerations for Treatment as Prevention: Subcategories, Codes, and Example Citations.^a

Subcategories	Codes	Example Citations
Patient health and well-being	Possible individual clinical gains	“Who can say, today, that above 500 CD4s, no deleterious effects of this virus are yet present?” (Expert Q, virologist) “What are we missing? It’s to show that the benefit [ …] does not simply exist intellectually but that it can be measured in clinical terms. But I am not sure that that is absolutely necessary because the indirect arguments, I’d call them, of the harmfulness of this process are well known, particularly, the state of inflammation that is often talked about today and that we clearly see can have deleterious effects.” (Expert D, clinician)
	Improved antiretroviral treatments	“There is an individual benefit to treating people early. In terms of their undesirable effects, overall, medications have changed a lot and treatments are more bearable, and concerning good treatments, there’s not much resistance and there’s a lot less lipodystrophy with new treatments. The arguments for not treating, even during primo-infection, are obsolete because treatments have completely changed and will continue to change. Furthermore, they will more and more be taken once daily and are well tolerated.” (Expert F, virologist)
	Possible medical breakthroughs	B.L.: “We test and then we treat?” Expert L (clinician): “Yes. Why do I say that? I say that because there’s a cohort in France called Optiprime. It’s people who have been treated during primo-infection [ …] and these people, clearly, after 5 years, 6 years, 7 years of treatment with completely undetectable viral loads [ …] stopped their treatments and, for some, nothing happens [ …] We can wonder, then, if nothing emerges over time, whether or not we have turned this retrovirus, HIV1, into an ancestral retrovirus through treatment [ …] There are those who dream of eradication [ …] That will be difficult, if not, utopian. But to create a virus that will resemble the virus of an integrated ancestral retrovirus, that, that seems to me more possible.”
	Reduction in fears/risks of infecting partner(s)	“I also see what’s happening in the field. One of the greatest sources of suffering, today, in people who live with the virus is fear of transmission. It curtails their sexuality. Even those who manage to protect themselves, it’s still not as good as it used to be. Knowing that we can’t transmit, knowing that if there’s an accident with the condom, it will not be a major risk for the one you’re with increases sex life quality to an incredible extent. So that too is an individual benefit [of ART]. We never talk about it enough but it’s an individual benefit.” (Expert C, ASO worker)
	Unknown/unproven individual clinical benefits	“You say: ‘We will reduce inflammation’ [ …] Beyond 500 CD4’s, I don’t know what that means because all of the research results available to date are not focused on patients with more than 500 CD4s.” (Expert A, clinician)
	Potential deleterious effects	“You are exposed to risks. Antiretroviral medications are monsters. They interfere with the organism’s biology. So there’s no way to imagine that all they do is destroy the virus and leave the rest intact. We clearly see that they do things to bone mineral density, to the kidneys, all that [ …] it’s a problem of balancing benefits-risks.” (Expert O, researcher)
Patient preparedness and choice	Patient demand	“He is one of the candidates who asked for treatment to avoid contaminating his partners [ …] he asked for treatment. There are quite a lot.” (Expert P, clinician)
	Unacceptability of deciding for patients	“We have to offer it, to give him free choice. That is what’s ethical: to provide [ …] the information available on the possible interest of using treatment irrespective of CD4 count [ …] people have a right to decide for themselves.” (Expert E, clinician)
	Patient acceptance	“I often share my views on these issues [individual and collective benefits of ART] with my patients and, today, the majority of patients choose treatment.” (Expert D, clinician)
	Patient readiness	“There is one thing that does not change and will not change; it’s that, no matter what, the best moment to begin treatment is when the person is ready [ …] it’s always been true and I believe that it’s [dependent on] factors that are linked to the person, factors that are linked to the doctor and factors that are also linked to society as a whole, factors which we can’t ignore.” (Expert D, clinician)

^a All citations presented are translations agreed upon by Bertrand Lebouché and Kim Engler.

Table 3.

Experts’ Collective Considerations for Treatment as Prevention: Subcategories, Codes, and Example Citations.

Subcategories	Codes	Example citations
HIV transmission risk	Its interpretation	“In the end, who [among the HIV-positive] is not at risk [of transmitting HIV]?” (Expert Q, virologist) “I have a few patients who are under treatment for preventive reasons since I know and they know and they accept that they don’t necessarily have protected relations in sex venues and I am doing risk-reduction.” (Expert S, clinician) “I do not distinguish between 900 and 500 [CD4’s]. It’s [ART for prevention] more of a discussion with the patient and their partner [ …] I also believe that it’s especially a point to discuss within a stable couple, more than with a person who has relations with different and multiple partners.” (Expert G, clinician)
	Its (in)sufficiency as a reason to treat	“As a sole indication for treatment, it’s not quite enough [ …] if there is no benefit for the individual. It’s an additional incentive, a parameter to take into account.” (Expert G, clinician) “I no longer hesitate one minute to treat a patient, not so much for themselves but for their partner or partners. Today, definitely, it’s an argument that I readily make. A patient who is part of a [sero-different] couple, for example, I explain that, for me, we must begin, even if they are not at all within the European, American or French criteria for initiating treatment.” (Expert N, clinician)
Impact on the epidemic	Likelihood of positive impacts	“There is an additional benefit that is absolutely decisive in this benefits-risks balance; it’s the impact of treatment on the risk of transmission that led to complete persuasion.” (Expert D, clinician) “If we give to test and treat the objective of diminishing the prevalence [of HIV], I’m not sure that we have properly looked at our chances of achieving a result in that regard.” (Expert O, researcher) “In any case, whether we must treat them immediately or in 1 or 2 years, that is not what will change, in a major way, the profile of the epidemic.” (Expert G, clinician)
	Potential barriers to success	“It’s questionable whether this collective approach will really be a convincing message for doctors and for patients.” (Expert R, virologist –on acceptability) “I have doubts about the overall efficacy of test and treat in homos[exuals]. I think that we have to try it because it’s an existing method [of prevention] but I have doubts about its efficacy because of behaviors, because of STIs, because of the fact that it’s anal intercourse, because … and also because of, of the desire to free themselves of preventive control over their sexuality.” (Expert I, researcher)
	HIV testing as the priority	“Only 6% do not fit [within the French treatment guidelines] and the reason they do not fit is because they have more than 500 CD4’s [ …] and these 6%, we treat them within 2 years. So we must stop talking about test and treat. We must mostly talk about tests [ …] we don’t screen well.” (Expert B, clinician) “‘Test and Treat’ means nothing if we test people and find them at 80 [years old].” (Expert J, clinician)
Cost	Cost-effectiveness	“I think that we have quite a bit of data that is in line with treatment diminishing transmission [ …] But I think that we don’t have sufficient data that are convincing to OMS-type health authorities [ …] furthermore, there are no studies from an economic point of view that allow us to say that it is worth it from an economic point of view to treat much more people to diminish transmission. We have no cost-effectiveness studies.” (Expert C, ASO worker) “For the cost for society, well, we must be reasonable. We will not give a treatment that costs 600 or 700 Euros per month to avoid using a condom that costs 1 Euro or 50 centimes. It becomes completely unreasonable.” (Expert G, clinician)

^a All citations presented are translations agreed upon by Bertrand Lebouché and Kim Engler.

Considering the Individual in ART for Prevention

Patient health and well-being

Most experts addressed considerations related to patient health and well-being (16; 84%). Six codes compose this subcategory of individual considerations. Experts advanced that “arguments” supported the possibility of individual clinical gains from early ART, which, for some, were either sufficient reason to treat early or becoming more and more numerous (eg, inflammation theory, normalization of CD4 counts, reduction/elimination of viral load, improvement in quality of life). Only 1 expert stated that there were “scientific proofs” of these gains. Experts also mentioned the unknown or potentially negative effects of having a replicating and/or expanding virus in the absence of treatment. A second issue often emphasized was that ARTs have improved (eg, they are less toxic, offer lower probabilities of resistance, are better tolerated, easier to take, and cause less lipodystrophy). Two experts spoke of the possibility of medical breakthroughs via early ART (ie, converting HIV type 1 into an ancestral retrovirus; eradicating HIV reservoirs) and 2 others highlighted ART’s role in the reduction of patients’ fears and risk of infecting their partner/partners, providing well-being-enhancing reassurance through its impact on viral load and infectiousness.

Experts also provided reasons for not treating early, pointing to the unknown, unproven (or not sufficiently so), or not unanimously accepted interest of early ART in terms of individual clinical benefits (eg, on inflammation and its associated complications, morbidity) as well as the potential deleterious effects of ART, particularly, in the long term (eg, toxicity, reduced efficacy after decades of use).

Patient preparedness and choice

Patient preparedness and choice was the second most important subcategory of individual-focused considerations. Over half (11; 58%) of the experts mentioned this issue and, many, in regard to the often discounted assumption that individuals would not be ready for, accept, or want early treatment for prevention. Four codes compose this subcategory.

The issue of patient demand was mainly broached to underscore that patients are indeed demanding treatment for prevention. Experts described cases of individuals seeking treatment, because they wanted peace of mind, had difficulty with/were not practicing safer sex, did not want to infect their partners, and/or wanted to limit their infectiousness. Experts contributing to this subcategory did not agree, however, on the extent of demand for preventive ART, generating a range of characterizations from “a lot” to “marginal.”

Deciding for patients either by forcing, imposing, or not honoring the right to refuse ART for prevention or, conversely, by not allowing freedom of choice by not informing patients about it was emphasized as unacceptable or unethical by some experts. Often, these aspects of patient choice were raised against the notion that a test and treat strategy would require universal treatment, if not, treating patients against their will.

Patient acceptance of preventive ART was especially broached in terms of the role of doctors in facilitating it. Experts proposed that provided the clinician was convinced of its advantages and/or adequately explained these to their patient, acceptance would generally be forthcoming. That acceptance might vary depending on the patient (eg, perhaps more likely if they are part of a sero-different couple) was pointed out by 1 expert.

Finally, a few (3) experts discussed patient readiness in regard to preventive ART, presenting it as either the best condition in which to initiate treatment, as possibly requiring time to develop, or, in its absence, as a reason not to begin treatment.

Considering the Collective in ART for Prevention

Another central analytical category in experts’ discussion of early ART for prevention was collective considerations. Its subcategories are (sexual) HIV transmission risk, impact on the epidemic, and cost.

HIV transmission risk

Regarding HIV transmission risk (15; 78.9%), composed of 2 codes, many experts acknowledged ART’s potential to reduce the risk of sexual transmission to partners and explained that current French recommendations permitted ART for those with a CD4 count of more than 500 cells/mm³ if there was risk of transmission or unprotected sexual behavior (among other reasons to initiate treatment at this stage). Experts diverged, however, in their interpretation of risk in terms of the features of those who would be appropriate candidates for preventive ART due to their transmission risk. Several mentioned sero-different couples (where 1 partner is HIV positive and the other is HIV negative) as candidates for preventive ART (5), particularly if they were not using protection systematically. Other characteristics associated with candidature for preventive ART, which could be combined, were being a sex worker, of foreign origin, a gay man, having multiple partners, using sex venues, engaging in unprotected sex, and simply being HIV positive. Interestingly, behavioral features associated with suboptimal candidature for preventive ART included 2 of these: engaging in unprotected sex (ie, arguing that prevention overall is unlikely to succeed in this context) and having multiple partners (arguing that individuals part of a sero-different couple are more appropriate candidates). Two experts underscored that homosexual/gay men with many partners or who did not practice safer sex were not well integrated into the French recommendations on transmission risk, which might partially explain these contradictions.

Experts also disagreed on prevention’s sufficiency as a reason to treat. Some emphasized that individual considerations had priority over those of the collective, with the HIV-positive person’s health taking precedence over benefits for partner or population health. In this context, HIV prevention as an indication for treatment was allowed as long as clinical gains were also likely or as “the cherry on the cake,” as 2 experts stated. Conversely, others were favorable to treating patients early with ART for the sole purpose of protecting partners.

Impact on the epidemic

The subcategory, impact on the epidemic (17; 89.5%), has 3 component codes and relates, in part, to the perceived likelihood of positive impacts of early ART (alone or within a test and treat strategy) on the HIV epidemic and public health. Experts varied on this issue. A positive impact on the epidemic, often discussed in terms of “collective benefit,” was deemed probable to certain by 7 experts. Positive impacts were characterized in terms of a reduction in the propagation, diffusion, incidence, or transmission of HIV and/or in the prevalence or circulation of resistant strains of the virus. For 5 experts, positive effects were unknown, as yet, poorly defined, or in need of further investigation, and others (4) believed that significant positive impacts on the HIV epidemic were unlikely Utopian.

Specific potential barriers to early treatment’s successful impact on the epidemic were mentioned by several experts (7). These related primarily to issues of early treatment acceptance (alone or as part of a test and treat strategy), adherence (eg, the selection of people into treatment who are refractory to HIV prevention; if people are poorly treated, there is a risk of emerging mutation; difficulties in maintaining long-term adherence), behavioral modifications as a result of the strategy (eg, increases in sexual risk practices); the possible role of primo infections in maintaining the epidemic; and potential blips in viral load (eg, provoked by STI). Experts could mention the possibility of group differences in potential barriers and their being problematic, specifically, in the population of gay men. Hence, some less favorable expectations about early treatment’s impact on the epidemic referred to the HIV epidemic in gay men or men who have sex with men (MSM). Other impediments to treatment’s impact on the epidemic concerned a view of HIV testing as the priority (9). Several experts pointed out that, under French guidelines, only a small minority of current patients are not treated and could be considered strictly for early preventive treatment (eg, “peanuts”). For some, this was directly related to inadequate testing to uncover more HIV-positive individuals at earlier stages of infection. Many experts more generally advanced that increasing the availability of testing was a greater priority than early treatment for dealing with the epidemic.

Cost

The final subcategory of collective considerations was cost, briefly broached by 3 (15.8%) experts and related to either the unknown or the non-cost-effectiveness of preventive ART (eg, when compared to the price of condoms).

Weighing the Merits of Early ART for Prevention in the Face of Uncertainties

How experts typically discussed the above considerations is best described as a weighing of the merits of ART for prevention in the face of uncertainties. Several experts spoke directly of a “problem,” “measure,” “balance,” “opposition,” or “appreciation” (or other variation) of “benefits–risks” in regard to early preventive ART whether for the individual, the collective, or both.

Experts varied in terms of how they resolved this weighing. Experts could believe, for example, in both individual and collective benefits; they could be more convinced of the individual than the collective benefits, or they could be more convinced of the collective than the individual benefit. Constant, however, is the consideration of multiple individual and/or collective factors as well as recognition of uncertainties in regard to early ART.

Uncertainty, as used here, is not meant to necessarily connote something negative or antonymic to hope.²³ Experts could claim to be favorable to widespread early ART (or treatment irrespective of CD4 count) despite recognition of uncertainties. Uncertainty refers to both possible limitations and positive potentials of early ART for the individual and the collective, particularly in terms of health, and to factors that may intervene or interfere with early ART use (eg, patient preparedness and choice, potential barriers). Uncertainties were indicated in myriad ways throughout the interviews, for example, through talk of risks, mention of lacking knowledge/research, and what can be termed experts’ “modality choices,” indicating something less than assertion.²⁴ Markers of modality include such terms as probably, potential, maybe, may, could, should, and possibly and several labels given to our analytical codes contain such terms.

Discussion

Our qualitative analyses suggest that for most French HIV experts in this study, the decision to treat early or universally for prevention is not a simple one. Multiple and complex individual and collective factors are considered and, regularly, the rapport between them. The interviews underscore what has been advanced by others that moving forward with treatment as prevention means keeping in mind both the individual and the societal good.²⁵ Experts’ many uncertainties, however, suggest that the benefits on both levels remain a matter of debate.

Patient Centeredness

On an individual level, a prominent consideration for experts was patient health and well-being, which centered on the different clinical implications of ART or its absence. Despite the potential benefit to public health of early or universal ART, the health and well-being of people living with HIV is clearly at the forefront of concerns.² For example, in a study by Kurth et al¹⁸ on ART-prescribing clinicians’ attitudes toward early ART, although almost all (94.5%) respondents agreed that it can slow the spread of HIV in a community, the vast majority (92.0%) initiated ART for the patients’ own health and based on their readiness to take it.

The subcategory of patient health and well-being also included ART’s ability to reassure and lessen patients’ fears of transmitting the virus. A survey among the UK MSM found that 37.3% worry about passing on HIV to their partners, and that these worries are more common among men not on ART.²⁶ As others have highlighted, transmission fears, a motivator for the production of the controversial Swiss Statement, can interfere with the ability of people living with HIV to achieve aspects of a “normal” sex life,²⁷ including sexual pleasure, sexual intimacy, and procreation, if desired.²⁸ Hence, early ART could play a significant role in improving the sexual health and sexual well-being of people living with HIV.

As to patient preparedness and choice, the second subcategory of individual considerations, while discussions of universal treatment have been criticized for not attending to patient readiness,⁹ in contrast, experts interviewed in our study spoke directly not only of patient readiness but especially of the patient demand, acceptance, and decision in regard to early ART. Indeed, several experts wanted to see French patients have greater decisional power in regard to ART for prevention and, for some, patient choice was served by clinicians’ informing HIV-positive individuals about the preventive potential of ART. Such a shift in decisional power has occurred, for example, in the British HIV Association’s latest draft guidelines for ART among adults,¹ which recommend that clinicians present to all patients the evidence that ART lowers the risk of transmission and that willing patients with CD4 count exceeding 350 cells/mm³ be accorded preventive treatment.

Variable Views on Early ART’s Collective Issues

Experts’ collective considerations were of 3 types. One, HIV transmission risk, contained heterogeneous views that spoke to the dilemma for experts of identifying appropriate candidates for early preventive ART (ie, Who is a transmission risk for others?) and whether HIV risk and the protection of others is reason enough to start the treatment early. HIV-positive individuals in sero-different couples were, on several occasions, presented as prototypical candidates for preventive ART. Experts disagreed on other profiles, including male homosexuality/gay identity and having multiple partners. This may be because little information on the preventive effect of ART in people living with HIV exists beyond sero-different couples and mother-to-child transmission,²⁹ and preventive ART’s legitimacy in these contexts is well established.

In France, where 47% of new infections in 2010 occurred in MSM, a group in which new infections rose between 2003 and 2010,³⁰ our findings on transmission risk suggest that there is a need for more deliberation to guide identification of target populations or candidates for early ART for HIV prevention. The literature has begun to explore strategies to identify priority groups to optimize the impact of early TasP (eg, expanding ART based on epidemiological impact, clinical impact, affordability/cost-effectiveness, feasibility, and acceptability).³¹ In France, more research on specific populations with HIV, including MSM, that provides empirical data on key behaviors (eg, ART uptake and adherence, sexual practices), would be helpful to estimate the preventive benefits of early ART.

The expected impact of early ART on the epidemic, another collective consideration, also had a range of views, with many experts identifying potential barriers to positive benefits. This parallels the current equivocal evidence base on the population-level effect of treatment as prevention in high-income countries.³² Furthermore, several of the experts interviewed favored improving HIV screening over early treatment (eg, to reduce the number of undiagnosed HIV-infected people, to detect them earlier) as a means of addressing the epidemic, a notion supported by others.^32,33 In France, it is estimated that 29 000 individuals have an undiagnosed HIV infection,³⁴ and although treatment is recommended in patients with a CD4 count of less than 500 cells/mm³, 30% of the new HIV diagnoses are among people living with HIV in a late stage of the disease (AIDS or less than 200 cells/mm³).³⁵ Improving this situation seems an important prerequisite of successful TasP in France.³⁶

Uncertainty

Experts’ uncertainties (expressed risk, potentials, unknowns, etc) surrounding early ART for HIV prevention is a key observation of this study. Although managing uncertainty and weighing benefits–risks is a recognized part of HIV medical practice,^3,37 many agree, for example, that the magnitude of long-term therapeutic benefits of ART at higher CD4 counts is uncertain.³¹ Tellingly, in a survey of Australian ART prescribers, only 4.6% most strongly recommended ART initiation irrespective of CD4 count.²⁰ Quite possibly, no sooner than 2015 will results of the international and multisite Strategic Timing of AntiRetroviral Treatment (START) randomized trial be available on the clinical interest (risks and benefits) of treatment for HIV-infected people with CD4 counts of more than 500 cells/mm³.³⁸

Despite uncertainties, several of our study’s experts were ultimately favorable to early ART to treatment, irrespective of CD4 count, or to moving forward with a test and treat strategy. High-profile proponents of these approaches have themselves acknowledged important uncertainties. For example, Montaner^39(p209) has stated that “unequivocal answers are urgently needed” (eg, as to the utility of universal treatment), while Cohen^40(p1323) has urged pause and reflection, given that “The protection provided from ART is not absolute and is not absolutely predictable.” Having established that ART dramatically decreases HIV transmission in sero-different, mainly heterosexual couples in a clinical trial setting,⁴¹ a current objective of HPTN 052 is indeed to examine the durability of this protective effect of ART.⁴²

The capacity of scientific evidence to eliminate uncertainty when assessing health risks is, however, partially limited by the unpredictability of people’s health behaviors.⁴³ Whether people would accept and adhere to preventive ART or modify their sexual practices (risk compensation) as a result of it were questions raised by the experts and deemed potential barriers to a successful public health impact of preventive ART on the HIV epidemic. These speak to concerns about the “real-world” implementation and repercussions of TasP, beyond clinical trial contexts and optimistic modeling, and the results of ecological studies on indicators of antiretroviral use and community viral load have been mixed in this regard.⁴⁴

Limitations

This study has limitations. The sample is one of convenience and is not necessarily representative of the full range of French expertise on HIV or of experts within each area of expertise. It likely overrepresents high-profile experts in the field, HIV clinicians (57.9% of the sample), and experts working in Paris (84.2% of the sample). Paris is disproportionately affected by the HIV epidemic. The number of new HIV cases in the Île-de-France region, consisting largely of the Paris metropolitan area, was over twice that of the national average in 2009 (24.3 versus 10.1 per 100 000 inhabitants), and 49% of 2010’s reported AIDS cases in France were tied to the region.⁴⁵ Furthermore, medical expertise, in general, is more highly concentrated in this region, containing, for example, a greater than average density of doctors (ie, 362.4 versus 306.2 doctors per 100 000 inhabitants).⁴⁶ Our findings must thus be weighed in relation to these sample biases. Other limitations of our study include the possibility that experts’ views may have changed in regard to TasP, given developments in HIV knowledge since February 2011, when interviewing began. Nevertheless, many issues raised by participants remain pertinent to discussions of TasP, and this study adds to a budding area of investigation concerned with different stakeholders’ attitudes toward early ART.^18,47

Conclusion

This interview-based study with French HIV experts offers an uncommon qualitative perspective on TasP and the issues it raises for individuals and the collective. It showcases the complexity of French experts’ considerations when weighing the merits of early ART for prevention, and uncertainties about this approach, whether invested with promise or precariousness. Our findings raise doubts about the general acceptability and immediate feasibility of widespread implementation of TasP in France, based on early or universal ART in people living with HIV. This seems consistent with the delayed revisions of HIV treatment guidelines in France,¹⁷ which are now expected in the summer of 2013.⁴⁸ The range of concerns expressed by experts also points to TasP needing to be part of a comprehensive HIV-prevention program (eg, with expanded HIV testing, supports for ART adherence, sexual, and risk behavior interventions).

Footnotes

Acknowledgments

We wish to acknowledge the sponsor of this study, the Research Institute of the McGill University Health Centre. Warm thanks are extended to the study participants.

Authors’ Note

Merck Dhome Chibret France provided approximately 60 000 Euros to the McGill University Health Centre Research Institute (study sponsor) of which a portion went toward the funding of the study leading to the contribution. Merck Dhome Chibret France also paid the first author approximately 1000 Euros to promote the study's findings at the French national day of continuing education for doctors (ie, Dépister pour traiter: du diagnostic précoce au traitement à long terme, February 14, 2013, Pavillon Vendôme, Paris).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was made possible by a post-doctoral fellowship awarded to B.L. by the CIHR Canadian HIV Trials Network and an unrestricted educational fund provided by Merck Dhome Chibret France also to B.L.

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French HIV Experts on Early Antiretroviral Treatment for Prevention

Abstract

Keywords

Introduction

Methods

Participants

The Interview

Ethics Approval

Qualitative Analysis

Results

Considering the Individual in ART for Prevention

Patient health and well-being

Patient preparedness and choice

Considering the Collective in ART for Prevention

HIV transmission risk

Impact on the epidemic

Cost

Weighing the Merits of Early ART for Prevention in the Face of Uncertainties

Discussion

Patient Centeredness

Variable Views on Early ART’s Collective Issues

Uncertainty

Limitations

Conclusion

Footnotes

Acknowledgments

Authors’ Note

Declaration of Conflicting Interests

Funding

References