Male partner influence on women's HIV prevention trial participation and use of pre-exposure prophylaxis: the importance of “understanding”

Background

Globally women are at increased risk of HIV acquisition, and an important HIV prevention research priority has been the identification of safe and effective methods that women can use without the assistance or even knowledge of their male partners, thereby protecting themselves in settings where condom use is not feasible. Although theoretically these products are “female-initiated” there is widespread evidence from trials in sub-Saharan Africa that many women's ability and willingness to join HIV prevention research studies, and to use investigational products, is influenced by their male sexual partners.^1-3 There is also evidence that many women regard their partner's knowledge and involvement in the use of female-initiated HIV prevention as desirable and culturally appropriate. Further, many large multisite HIV prevention trials are conducted in areas where women are marginalized in terms of decision-making around reproductive health and access to resources. Indeed, much of the impetus to develop effective, female-initiated, male-condom alternatives for disease prevention originated from the challenge that women are disproportionately at risk for HIV acquisition, and in many settings, they have limited power and ability to protect themselves.^{4, 5} It is a noted irony that despite the intent to develop a product for women to control and use autonomously, use of female-initiated prevention methods, at least in research studies, is heavily affected by the influence of male partner attitudes and behavior.^{2, 4} Less is known about male partners’ influence on women's use of oral Pre-Exposure Prophylaxis (PrEP). In randomized trials, oral PrEP is efficacious when consistently used. Qualitative findings from one of these studies that enrolled heterosexual serodiscordant couples showed that adherence is improved when partners, irrespective of gender, provide support. ^6-10

VOICE-C was an ancillary study to the Microbicide Trial Network VOICE multisite trial, conducted at the Johannesburg site. VOICE-C explored factors influencing women's use of study tablets (oral tenofovir, tenofovir-emtricitabine (Truvada™) or placebo) and vaginal gel (1% tenofovir gel or placebo).¹¹ In the VOICE trial, neither tablets nor gel were shown effective in preventing HIV acquisition. However, there is substantial evidence from post-trial pharmacokinetic testing that investigational products were widely under-used. Consistent with trial-wide over-reporting of adherence to study products, female VOICE-C participants (all enrolled in VOICE with HIV-negative status) demonstrated a reluctance to divulge the circumstances of product nonuse in qualitative interviews. Analysis of their narratives, however, revealed three recurring salient themes related to product-use experience including ambivalence towards research, preserving a healthy status, and managing social relationships.¹² While a qualitative enquiry is not meant to provide precise quantitative assessment of the relative importance of different factors on an outcome, it was clear that within each of these thematic areas, VOICE-C participants’ male partners had a substantial influence on women's product use.

In this paper we aim to characterize the direct and indirect influences of male partners on women's HIV PrEP trial participation and study product use and to describe the pathways through which male partners exercise this influence. Insights from this analysis can be used to develop intervention approaches or strategies for male engagement in future research and programmatic activities of microbicide or other HIV prevention methods.

Methods

The VOICE-C ancillary study was conducted from July 2010 to August 2012 at the VOICE clinical-trial site operated by the Wits Reproductive Health and HIV Research Institute (WRHI) in Hillbrow, a neighborhood in central Johannesburg, South Africa. Briefly, The VOICE trial was a phase IIB, double-blind, five-arm randomized, placebo-controlled PrEP trial evaluating the safety and effectiveness of once-daily oral tenofovir (TDF) and co-formulated TDF/FTC (Truvada™) (tablet group) or once-daily vaginal tenofovir gel (gel group) for women at 15 sites in Uganda, Zimbabwe, and South Africa ¹¹ (ClinicalTrials.gov NCT00705679). At the WRHI site 354 women were enrolled into the VOICE trial between July 2010 and August 2012. Male partners of VOICE participants were permitted and encouraged to come to the clinic for education and/or HIV counseling and testing services.

Guided by a socio-ecological framework which examines different spheres of external influence on individual behavior, ^13-16 VOICE-C explored factors operating at the community, organizational, and household-level that influenced VOICE trial participant's use of their randomly assigned study products (gel or tablets). To explore these issues, the study collected data from different groups of participants as described elsewhere,¹² using a variety of qualitative methods. This paper focuses on data from female VOICE participants and their male partners who were interviewed using: in-depth interviews (IDI; n= 41 women, n=14 men); serial ethnographic interviews (EI; n= 21 women); and focus group discussions (FGD; n=40 women in 7 groups, n=8 men in 2 groups).

A subset of randomly pre-selected VOICE participants was approached for screening and enrollment into VOICE-C on or after their Month 3 visit in the VOICE trial and randomized to the data collection modalities of IDI, EI or FGD. Of the 144 women screened, 106 were enrolled and 102 completed their interview(s). Following provision of female participants’ written permission for contact, male partners (MP) who she reported to be a “current” sexual partner were recruited. Fifty percent (n = 53) of VOICE-C women agreed for a male partner to be contacted for study participation, however more than half of these men expressed disinterest or unavailability to participate. Ultimately, 22 male partners of VOICE participants were interviewed in an IDI or FGD setting and 102 female VOICE participants in an IDI, EI or FGD. We explored male partners’ multifaceted roles and the pathways of influence on women's product use using semi-structured interview guides. Participants were interviewed by a gender-matched interviewer who spoke the local language of IsiZulu, SeSotho and/or English. Interviews were audiotaped, and data were subsequently transcribed, translated and coded in Nvivo 9 (Burlington, MA). Coding followed a structured codebook that was developed iteratively by qualitative analysts at the data center at RTI International in the United States and the research team at Wits RHI. The codebook contained 33 major (“parent”) codes, 12 of which were sub-divided into 36 minor (“child”) codes. Of these, a subset of fourteen were designated as “key codes” because they were most representative of the study objectives, and these were used to establish intercoder reliability of >80% across a minimum of 10% of transcripts. Coded data were then concatenated into coding reports by thematic area (e.g. MALE PARTNERS and PRODUCT USE) and summarized by analysts. Transcripts of male and female participants were analyzed separately. In addition to the regular coding consistency checks, the coding team and co-authors met regularly to discuss interpretation of results. Pseudonyms were chosen by each individual participant or assigned later by the research team to delineate quotations. Redundant or non-illustrative text in the quotations presented was removed by the authors and is indicated by square brackets and ellipses: [...]. Local terms, jargon or nonspecific text have been replaced or clarified by the authors in square brackets.

The study protocol was reviewed and approved by the Institutional Review Boards at RTI International and the Human Research Ethics Committee of the University of the Witwatersrand, and overseen by the regulatory infrastructure of the National Institutes of Health and MTN. The study was monitored at approximately 6-month intervals by FHI 360 and RTI.

RESULTS

Study Population Characteristics

Table 1 presents the demographic characteristics of the analytic sample. Women in the study were on average 26.8 years old (range 19-40), whereas male partners were slightly older (mean age 31.4, range 22-45). 96% of women had a primary sex partner although only 22% were married to him. All male partners had a primary sex partner, and 41% of those who agreed to participate were married. Approximately two-thirds of both male partners and study women had completed secondary school; and whereas just over half of the study women were earning an income (57%), more than four-fifths (82%) of male partners were. A minority of study women (29%) and male partners (23%) identified their current residence in Johannesburg as ‘home’, indicating a high-level of national and international migration within this study population. As previously reported, the 102 VOICE-C study women had similar baseline characteristics to the other 252 VOICE participants at the Johannesburg site.^{11, 12}

Table 1.

Demographic characteristics of Women and Male Partners

Characteristics	Women		Male Partners
	n=102	%	n=22	%
Age (mean, range)	26.8 (19-40)		31.4 (22-45)
Currently married	22	22%	9	41%
Currently has primary sex partner1	98	96%	22	100%
Currently living with primary sex partner1	44	43%	16	73%
Parity (mean, range)	1.2 (0-4)		1.4 (0-5)
Number of children takes care of (mean, range)	2.1 (0-7)		2.3 (0-5)
Completed Secondary school or more	69	68%	14	64%
Income status
Doesn't earn an income	44	43%	4	18%
Formal employment	52	51%	16	72%
Self-employment	2	2%	2	9%
Other	4	4%	0	0%
Ethnic group
Zulu	27	26%	4	18%
Xhosa	13	13%	3	14%
Sotho	19	19%	2	9%
Ndebele	26	25%	4	18%
Other*	17	17%	9	41%
Religion
Christian	94	92%	17	77%
Muslim	0	0%	2	9%
Other/none	8	8%	3	14%
Regularly attends religious services (1+/week)	85	83%	10	50%
Current residence is “home”	30	29%	5	23%
Number of yrs. lived in current residence (mean, range)	8.9 (0-39)		9.2 (0-26)
Previously involved with HIV research/work	43	42%	5	23%
Interview mode assignment
IDI	28	27%	14	64%
EI	24	24%	NA	NA
FGD	50	49%	8	36%
Type of interviews received
IDI	41	40%	14	64%
EI	21	21%	0	0%
FGD	40	39%	8	36%

¹“Primary partner” was defined here as “a person you have sex with on a regular basis or who you consider to be your main partner”

Overview of Male Partner Understanding

Throughout the data, a predominant theme of male partners’ level of “understanding” pervaded as a central explanation for how male partners influence their female partners’ trial participation. Male partners’ “understanding” - or lack thereof - was described as having a critical direct and indirect influence on women's trial participation and product use. Of note, this influence, as described in participants’ narratives, varied little in regards to whether women were assigned to the gel or tablet groups of the study. Further, while “trial participation” and “product use” were distinct domains of inquiry to the research team, it was evident in participants’ narratives that the study and product use were inextricably linked. More simply put, male support for joining the study was consistent with his support for taking the product. The meaning behind “understanding” in this context was described by male partners and study women in two important and complementary ways: 1) “comprehension” of the purpose of the research study and the mechanism of action and potential side effects of the study products [understanda in isiZulu], and 2) “support/ agreeability” for their female partners being study participants and using products [kumelana in isiZulu]. During analysis a third and subtler dimension emerged whereby the meaning seemed to suggest that men's “understanding” was symbolic of men's acceptance of larger shifts in gender roles and relationship power, and the potential implications that women's increased access to health information, knowledge and prevention products – relative to their male partners -- might have.

Male partners’ “understanding” (comprehension) of research

Both male and female participants in VOICE-C stated that male partners lacked comprehension of several aspects of the VOICE trial. This led to suspicion about the trial and reluctance to allow partners’ participation and product use. Aspects of the VOICE study that male partners did not comprehend spanned a range of study design and product-related issues, such as why the research was being conducted with Black participants in South Africa, the rationale for ARV-based PrEP – specifically, testing ARV-based products on HIV-negative volunteers, disbelief about the ability to measure product effectiveness if condoms were to be used for every sex act as directed; fears about potential side effects of the products and confusion about the mechanisms of action of the pharmaceutical agents. Men communicated their suspicions regarding the research and products, and this likely created a discouraging outlook for women of the VOICE study and product use. More directly, men refused or disallowed women to participate in the trial or use her gel or tablets. One woman described the particularly contentious feelings of her partner that were emblematic both of suspicions of research and White people:

He was complaining and saying that these study people [researchers] were playing with us. He said, “They were just using us, Whites were playing with us as Black people and they chose us as Black people of South Africa because they knew that we are poor and there's too much HIV/AIDS within our country, so that's why they did this to us.” So, he has a serious problem with White people. (Thandi: Female EI participant, Gel).

Additionally, many male partners were suspicious that their female partners were HIV positive because of their involvement in the study, and women expressed a similar view. Male partners were challenged to comprehend why their partners would use an antiretroviral if they were not “sick” (HIV infected). Information sheets, facts sheets and the informed consent forms brought home as part of VOICE trial participation did not always help: the materials may have been difficult to comprehend and included scientific terms about study design and investigational products, and referenced HIV, thereby possibly fueling male partners‘ reservations, as this female participant described:

My boyfriend left me because of the study...He told me that he doesn't believe me because he doesn't know what the tablets are for. I gave him the form [Informed Consent] to read and he told me that he doesn't understand what is written on the form. He told me that the form talks about people who are HIV positive and those who are not HIV negative, so he doesn't understand what is in the form. He then asked me that we must separate. I told him I do not have a problem. I did not stop coming to the study, I continued coming to the clinic. (Carter: Female FGD participant, Tablet)

By contrast, for other men and women, the information leaflets provided by the VOICE trial helped male partners better comprehend the purpose of the study – perhaps offering a legitimization, corroboration or simply clarification of information previously communicated by the female partner. This did seem to help facilitate open conversation about a potentially sensitive topic and address some initial concerns, as indicated by the following participant:

When I say to him these tablets are taken by people with HIV and he says maybe I am also sick. I know he is just joking. He did say so about those ones [tablets] and I showed him the forms [trial information sheet] and he understood. (Refiloe: Female IDI participant, Tablet)

In men's narratives, additional evidence emerges about their distrust and lack of understanding or knowledge about the research or the purpose of using the study products. Men's initial reactions seemed to suggest their lack of trust of the true intentions of the research, for example whether it was a “legitimate” operation that had been authorized by the South African government. They also frequently questioned whether the research products would have any long-term side effects, particularly in relation to fertility. Men described having heard through the media or through anecdotes about “fake” investigational products, false HIV test results and controversial messages from government officials that questioned the etiology of HIV. The following passage from a male participant articulates well his feelings of generalized mistrust for research:

At first I was thinking that these tablets that she is swallowing would make her sick [...] because nowadays you cannot trust anyone, you see. That is why I even said at the beginning to her ‘as long as the tablets treat you well I don't have a problem that you attend the study’ [...] they [may] kill her [laughs], sometimes those kinds of things do happen [...] Because like we do not know about the study and we do not know what is happening, you see [...] I said that I trust research, yes it's fine. But that thing [the research] must [...] like you have to be certain that those people are genuine researchers or are they are coming up with some criminal/shady intents [...] Like according to me, like I have heard that AIDS was spread [intentionally] [...] so how could you trust things like that. (Simba: Male Partner IDI participant, Tablet)

A component of this non-understanding, as outlined in the quotation below, related to questioning who was benefiting, again going so far as to express a fear that the study product might cause death to the volunteers:

With me like with the gel okay I never had a problem using the gel okay. I had a problem until I did understand what's the purpose of using the gel but at some stage even now I don't think like it was helping me[...] Even now I don't know whether this gel was protecting us or was killing us. (Thami: Male Partner FGD participant, Gel)

Indeed, in women's narratives, there were numerous descriptions of male partners’ misgivings of products – that “these things will make you sick” or make him sick. Sickness was associated both with risk of HIV acquisition and product ingredients that were suspected to cause uterine cancer, infertility, or more generalized “damage to the womb”. In one focus group discussion, female participants described partner's concerns in terms of men's fears that they would never be a “proper man” because the study gel may affect fertility. Men's fertility concerns provided potentially important insight into why men might have been particularly sensitive or suspicious about research insofar as it may have been perceived as affecting their masculine identity as procreators.

Male partners “understanding” of (support for or agreement with) research

Overall men's narratives endorsed the idea that if they knew more about the study, the products, and the research procedures, they would encourage or support product use and study participation by their female partners. Women, like the men, stressed the importance of disclosing and explaining use. A critical prerequisite to receiving support was women's disclosure of study participation and product use. The majority of women in the VOICE-C study had disclosed study participation and product use to various degrees to their male partners. Disclosure to male partners was perceived as particularly important – even imperative -- for married women. For those who were not married and/or not cohabitating with their partners, women's attitudes towards disclosure depended on the duration and level of commitment to the relationship, as well as their personal sense of obligation. Of women who disclosed, many described indirect and direct ways in which male partners supported their product use. The most commonly described direct influence was verbal reminders to take tablets or use gel. One woman said her partner encouraged her to use his cell phone alarm as a back up to hers. Another participant used her partner's cell phone alarm because she did not have a phone at the time. When men showed support in this way, they were often described as being “understanding”. Conversely, women who had not disclosed said that they had no one to help them to remember to take their tablets or gel, implying that male partners could have served as a useful support system.

One woman described how other women could not use products or be part of the study because they had not disclosed participation, nor fully explained the study, to their husbands or other people in their homes thereby generating resistance or lack of understanding about the research:

That is why most of them [women in the community] are not able to use the products and also [could not] come to the study because they did not tell people in [their] homes that they are coming to the study. It is not easy to take the tablets every day while you are not sick [...] because if you do not disclose they will be asking themselves what the products are for. When you have explained to your partner, he will understand why you are taking the tablets or the gel (Phumzile: Female IDI participant, Gel)

Another female participant stated the critical importance of written documentation for male partners’ understanding, because they were suspicious of women who verbally explained their tablet or gel use suggesting women were covering something up: either their HIV-positive status or their promiscuous behavior.

You know this thing [explaining the study and products] isn't easy like ABC. It can be easy as time goes on but not at first, there is no one [male partner] who can really accept [...] if he sees you entering with two bottles and you just tell him that, “No, I'm in a study.” Not every man can be that understanding unless you have got proof of something else that shows that you take the tablets because of one, two, and three. When you just speak to a man with your mouth only it's like you know, you are just joking or you are covering something else for your own benefit. Do you see that thing? It's not easy. (Nomsa, Female FGD participant, Tablet).

Men that became more familiar with the purpose of the study could become important peer supporters. The above participant (“Nomsa”) went on to describe how the study doctor – a position of authority in the research context - explained the study to her partner, which positively influenced their relationship and her product use. Here the doctor's explanation seemed to serve a dual purpose of providing more details and corroborating her story, lest her partner have suspicions about her telling the truth:

At first he would say, “Oh, this means that you are sick.” [...] until I was helped by the doctor who explained everything to him that, “You know, as I told him that I am attending this thing, what I am saying is true. This thing is for a study, they are doing like this and like that. That is whereby he became free and by that time he was then even encouraging me “Can you take your tablets now; it's now eight o'clock in the evening, don't forget your tablets.” He used to remind me to take the tablets even though at first he didn't understand this whole thing about the tablets but we ended up becoming good friends due to these tablets. (Nomsa: Female FGD participant, Tablet.

Male partner narratives corroborated women's accounts. One male partner clearly articulated the consequences of not understanding the study, specifically that he could not support his female partner to use the tablets if he was not properly informed about it: “Because I was not actually informed with this whole thing yet so it was just so I cannot encourage her on something that I don't understand exactly. (Sabelo: Male Partner IDI participant, Tablet, IDI). Conversely if men did have a proper understanding, they would be supportive and agreeable:

I don't have any much say. There's not much I can say because I understand why she has to take them so there cannot be any questions why you are taking them and all that stuff[...] Because I know what they are up to and the whole story about the tablets, (Michael: Male Partner IDI participant, Tablet)

Another female participant described how she did not encounter any resistance from her partner with regard to study participation, not necessarily because he comprehended the purpose of the study better, but perhaps because it was his nature to be cooperative and understanding -here synonymous with “not difficult”- more so than other men.

He did not have a problem, I told him that there is something I am doing, and it is a study being done here at Esselen. They want to prove that these tablets and the gel but I told him about my tablets that I am taking that they are trying to see whether they are able to prevent HIV[...]You see, he is not a difficult person, mhm he understands well (Mmakgomo: Female IDI participant, Tablet)

“Understanding” as an expression of acceptance

In some cases men may have viewed the trial and women's consequent access to health information, knowledge, services and/or preventative products as a threat to their power in the relationship and control over women's sexuality. Although men were not only allowed but also encouraged to visit the VOICE clinic, they were not enrolled as participants in the trial, and few male partners presented at the clinic for educational sessions, HIV testing or other activities organized for male partners. Most male partners had no direct contact with the clinic, and those who did only had brief interactions with clinic staff, and thus could not acquire the same knowledge, and perhaps more importantly, could not have the same experiences that women had through months of trial participation. Hence participation and product use became symbolically larger than simply having information about biomedicine and trials, as women actually experienced these new worlds from which men had been excluded. This may have exacerbated male partners’ unwillingness to understand, or to be agreeable towards, trial participation.

Indeed, as one male FGD participant explained, women bringing home study products might disrupt the pre-existing gender power dynamics in a relationship or household. In general, men described that it was preferable that they knew about and understood the study in advance, and ideally have the opportunity to weigh in on the decision for their female partner to participate. One man described how some men might react if their wives brought home products and requested to use them:

Now it depends on the understanding because I mean not every house has got an equal sharing of views. People can say they want to use this one [products]; because of this some men will just say “that's bullshit what are you talking about”[...] some men they say “you are my wife, I got married to you, so why are you telling me? I am the one who actually who [calls the shots] here”. (Antonio, Male Partner FGD participant, Gel)

A female participant further explained how the introduction of something new (e.g. a study, an investigational products) can cause problems, and raise unpleasant suspicions in the household. Male partners also acknowledged that many “other guys” disagreed with the concept of their female partners using HIV prevention products, fearing that it would facilitate promiscuity and infidelity.

Some husbands they have difficult minds and they don't understand like most of the things they don't want like to come to raise something that is going to be a big issue. Sometimes you see when you raise something you can discuss that the whole month and then somebody is going to be angry for the whole month. Well sometimes it's not easy for a woman to just come and implement that and “let's use the gel” it's going to be a lot of questions there, “why are we using this gel, are you cheating, are you doing this now, why now why not 12 years back?” you see, so it's difficult. (“Thami, Male FGD, Gel)

A female participant further explained that while the products might help women, they might also be problematic for men because they focus on protecting women, which can threaten gender-based power, and be perceived as inviting promiscuity:

You know if it can happen that this tablet can protect us as women then it can be a good thing and it can also be a bad thing, I can say that it can be a good thing to us as women and it can be a bad thing to the men because the tablet would be focusing on protecting us more than them and that would result in them always looking at us and watching us and that can result in a lot of divorces as well. (laughs) (Lilly: Female, FGD participant, Tablet).

Thus, importantly, “understanding” as “acceptance” may include a man's acceptance that women are at risk of acquiring HIV - from them –the main partner- or from another partner - both potentially threatening or frightening notions. This implicit lack of trust or threat of betrayal may make it difficult for men to accept the research, or be supportive of and cooperative towards female partners’ participation. A female participant explained the challenges of making the premises of clinical trials, which rely on population level risk, congruent with the specific circumstances of her own relationship:

I explained last time in such a way that he eventually understood. And he said ‘tell me what is it that you are protecting yourself from because I am your only partner. What are you protecting yourself from and how are the researchers going to see whether these tablets work because both of us are HIV negative?’ And I said to him ‘I am not the only one in the study - we are many; the results will show from those. There are many people in the study it is not necessarily that they will focus on me alone, do you understand? They use us, they utilize us to see, as we sometimes do not use condoms, and maybe you sleep around and I don't know about that, I cannot say I am guaranteed so those are the things they pick up in the study, so he understood. (Mary, Female IDI participant, Tablet)

Indeed, men may have feared what women's exposure to new ideas may question their sexual conduct, or that this would promote greater sexual freedoms for women. More generally speaking, as described below, VOICE participants’ experience at the research clinic may give women new perspectives on relationship dynamics and the social status quo.

And it makes the whole system [...] it's pointless for the lady to keep coming getting tablets, keep getting tested while the guy is at home, he's not getting tested, he's not getting anything. He's not having any knowledge... about anything else because coming here basically you know it gives you the idea of how life should be and what you must and must not do in your life. (“Jedson”, Male IDI participant, Tablet)

However, as this male partner is articulating, female study participants are accessing new information through research participation, and male partners are excluded from this, but the “system” will not change if he does not have access to, does not understand or is not included as part of a process that involves change in sexual behaviors and attitudes.

Engaging men through better understanding

When discussing PrEP use in general, and in the context of their own experience, men were aware of the role of male partner influence. Several said that other women would not use trial products if their male partners did not approve, and that this was contingent upon men's adequate comprehension. Thus “understanding” was described almost as a stepwise process whereby his knowledge was a prerequisite to his demonstration of “understanding” as support, which would ideally evolve into, a broader “acceptance”. Male partners were asked about the ways in which researchers could engage men to be more supportive of trial participation and product use. Corroborating the importance of men's knowledge and comprehension of the study, many men suggested more direct contact and the opportunity to clarify issues with staff, as articulated by the following two male IDI participants.:

If your programme can actually [allow]... two partners to engage in this programme and also like, for instance earlier you gave me a piece of paper for me to read... I think it will be probably more suitable if you [verbally] explain that this and this and this and if they have some questions they must raise them right there, and then you explain and you move forward. (Sabelo: Male Partner-Tablet, IDI))

I think like for fathers [men], maybe you can just try to find a person and talk to them then he also is able to give his reason why he doesn't want the woman to use these things [products]. Then try to explain to him what the reason for the woman to use those things and if he can have full information maybe he will be able to understand better than if he is told maybe like you pay him a visit once then talk to him and see what it is going to be like to him then he will also end up understanding clearly what is happening. (Vusi: Male Partner IDI participant, Tablet)

These again point to the central importance of initial comprehension and understanding to establish the foundation of the relationship between researchers and male partners.

DISCUSSION

We examined the influence of male partners on female participants’ experience with the VOICE trial and the use of investigational tablets and gels for HIV prevention at a clinical trial site in Johannesburg, South Africa. Narratives expressed during interviews and focus groups with women and their male partners were largely consistent regarding the indirect and direct influence of men's attitudes and behaviors on women's own attitudes and product-associated behaviors. This is similar to findings from other studies of microbicide or female-initiated methods for HIV prevention in which male partners and partnership dynamics are explored.^{3, 17-19} However, unlike previous studies, which have focused on more “downstream” product-related factors such as the effect of the gel on sexual pleasure, or the perception of men's acceptability of a product, our analysis here examined broader, arguably more fundamental issues underpinning men's support or lack thereof for women's research study participation and product use. In so doing, a consistent theme emerged: many male partners did not fully comprehend or trust research, and they may have found it to be threatening to their masculinities and relationship status quo. Lacking an accurate perspective, men may have been reluctant to support their female partners either by explicitly or implicitly discouraging product use or outright prohibiting partners’ use of the products or participation in the study. Further, women may have been reluctant to disclose product use to partners who may not agree, since this would have complicated and inhibited product use.

Thus while on the surface, “understanding” may appear to be a simple, and potentially easily modifiable factor – for example by providing information and written materials to male partners, our findings suggest that an experiential dimension of “understanding” that women, but not men, acquired through trial participation was more meaningful. Although most large scale clinical trials do make provisions and tacit invitations for male partners to come to study clinics, very few make this a priority, and there are limited resources in a busy research clinic environment to devote to this goal.²⁰ Further, some rightfully argue that efforts to engage men miss the essential point of encouraging female autonomy and are counter-productive to the mission of identifying an HIV prevention product that promote women's autonomy and agency. Indeed, this seemingly challenges the premise of “female-initiated” HIV prevention methods and microbicide research that originated as a strategy to bypass men's authority and help women at risk. Nevertheless, the results of this study are corroborated by findings from other qualitative studies conducted in the context of HIV prevention trials and suggest that the “cause” of female control is not women's primary concern. This suggests that more overt, direct engagement of male partners might be a worthwhile investment in women's adherence to HIV prevention technologies. This is also supported by results of interventions within HIV treatment research demonstrating the benefit of partner as adherence support “buddies”.²¹ Nevertheless, there is an inherent difference in the use of PrEP among serodiscordant couples, as in the Partners PrEP study, as compared to HIV prevention trials like VOICE. In the former, PrEP is not likely to challenge trust in the relationship, but rather to encourage greater intimacy by allowing for safer sex. By contrast in the latter, despite universal provision and promotion of male condom use, there is an inherent premise in HIV prevention trials enrolling HIV-negative women alone that a proportion will acquire HIV from a male partner through unprotected heterosexual sex. Use of PrEP among women with partners of negative or unknown status therefore might imply a lack of trust and potential infidelity on behalf of one or both partners – a stigmatization that has plagued male condom promotion efforts.

Overall men's narratives endorsed the concept that if men know more about the purpose of the research and the study products – particularly if they are given the opportunity for face-to-face interactions with professional staff from the clinic, they are more likely to encourage participation and product use by their partners. Men and women noted that this would allow for a firsthand opportunity to ask questions and get complete answers. Although not directly stated, this practice may also serve to make men feel “respected”, and preserve preconceptions of men as authoritative, particularly in a context where masculinities may be being challenged by broader societal transitions.²² Provision of a meeting place and forum for men to interact directly and in-person with study staff prior to or at their female partners’ enrollment visits – presuming that female participants are comfortable and consent to this -- may be a means to do this. Importantly, however, in the VOICE trial as well as in the VOICE-C study, as has been consistently reported elsewhere, it was difficult to recruit male partners to come to the clinic. Numerous reasons may contribute to this disconnect between men's reported desire for more direct involvement and interaction with clinical staff, and their absence in the clinic. Anecdotally, some male partners contacted for participation in this study equated study engagement with the expectation of testing for HIV, which they were reluctant to do. However, further examination of this issue is needed to identify other barriers and successfully address the paradox of men's apathy or disinterest when it comes to some health issues relative to their female partners along with simultaneously feeling stripped of the authority to provide permission or be involved in decision making about product use and trial participation.

Insofar as men's lack of “understanding”/ acceptance may be a reflection of broader resistance to changes in women's roles or gendered power, more creative approaches to enlisting male partner support for women's biomedical HIV prevention research may be required. For example, development of evidence-based concomitant interventions with male partners and men in research study communities to address gender norms and definitions of “masculinities”, including local views on paternity and fertility that may relate directly to investigational product use. While ostensibly this type of effort may seem beyond the scope of clinical research, many research networks have active community engagement staff and departments who may be able to direct attention to these efforts. Further, such efforts are consistent with the recognition that combination HIV prevention strategies are likely to be more effective platforms than “silo” interventions, and thus biomedical and behavioral interventions may be more effective when combined with interventions that address structural-level challenges such as how novel approaches threaten - or are threatened by – gender norms. That said, any research- or programmatic- based activity involving biomedical or bio-behavioral HIV prevention must not lose sight of women's right to safely and autonomously access prevention methods, with or without male partner knowledge. Indeed several women here, as in other studies, did not want to disclose product use to their male partners, for a variety of reasons, and this must be respected.

There are several limitations to this study. First, the men who presented for IDI and FGD are a selective group, and may be more supportive, than other partners of VOICE trial participants or men in the community. Indeed, about half of VOICE-C women refused to have their partners contacted, and although this response rate is similar to others studies, the reasons and nuances for why women refuse are not well documented. Nevertheless, the men participating here openly expressed many negative attitudes towards research and the products. As described in the methods, the majority of our study population did not consider Johannesburg to be their “home” and although we did not note differences by migratory status, it is unknown if the findings presented here would have differed among a predominantly “stable” population. Nevertheless, high levels of national and international migration are a reality in South Africa that must be considered in the planning for HIV prevention and treatment initiatives. Data from both male and female participants may have some degree of social desirability bias, despite the fact that the interviewers in this study were not part of the VOICE clinical staff, and efforts were made to establish rapport and encourage honest responses, and in the case of EI, conduct interviews in neutral locations. In particular, women may have attributed product nonuse to male partner influence as a socially acceptable way of reporting nonuse to research staff, even if this did not exist. Finally, qualitative research and analysis is by nature interpretative. To minimize this potential bias, we had a team of analysts coding the data, and regularly confirmed that the team maintained a high level of reliability in coding. The interpretation of data was likewise reviewed and discussed amongst a team of researchers to ensure that findings were adequately substantiated.

In conclusion, male partner influence was an important component of women's discourse on use of study gel and tablets at the Johannesburg VOICE trial site, and this influence was consistently expressed in terms of men's “understanding” -- synonymous with his comprehension of and/or agreeability with – the research. Participant narratives further revealed a deeper meaning of men's “understanding” that pertained to men's willingness to accept potential shifts in their relationship power as female partners accessed experiential knowledge through the trial. For women that wish to have their male partner involved in their use of HIV PrEP, research is needed to identify and test novel strategies to involve male partners in a more proactively rewarding and experiential manner.