**4. Existing prevention interventions for sero-discordant couples**

This section provides an overview of existing prevention and intervention programmes, that are implemented in the public and private health care systems as well as those implemented by civil society organisations.

#### **4.1. Current couple-centred HIV prevention services**

reported that among adults aged 15–59 years old, 86.0% were aware of their HIV status, of those 65.0% were currently on treatment, while of those who are on treatment 81% were

The current 2017–2022 NSP proposes a focus on social and behavioural aspects of HIV/AIDS and TB that prioritises a research agenda. This includes a commitment to having dedicated research funding for these health issues, build capacity to conduct research, and to identify better ways to collect and disseminate research findings. In addition, the plan acknowledges that we cannot simply treat our way out of the HIV epidemic, but that prevention strategies

While the NSP 2017–2022 stipulates the importance of Social Science and Humanities research in the 5 year plan, the proposed research foci continue to hover around understanding the

would offer the best response to curbing the HIV and TB epidemic.

virally suppressed (see **Figure 2**).

32 Advances in HIV and AIDS Control

**Figure 1.** Key targets of the 90-90-90 HIV treatment strategy.

**Figure 2.** Progress towards the 90-90-90 HIV treatment strategy.

The prevalence of sero-discordance among romantic relationships is growing in South Africa for various reasons [6]. What is concerning is the fact that, in the country and globally, it has been documented that HIV is most commonly transmitted between partners who are in a committed relationship [6]. This ultimately raises important issues including the risk of infection, reproductive choices and stress and change in the relationship dynamics. Despite the salience of couple relationships, existing HIV prevention interventions mainly focus on individuals instead of couples as a unit [19]. This negates the significant influence that couples play on each other's behaviour. There is growing agreement on the fact that prevention interventions and research should be aimed at couples as a unit to bring about change and maintain discordance. Couples-focused programs could concurrently include both dyad members, target each member separately and alone, in other instances might involve a combination of both modalities. The World Health Organisation has set out specific prevention interventions for couples with respect to their sero-status [20]. **Figure 3** lists the interventions that are specific for sero-discordant couples be it whether the male or female is the index partner.

#### *4.1.1. Case identification through HIV testing services (HTS) for couples*

Paying closer attention to literature pertaining to HIV Testing Services, couples counselling and testing are especially important for identifying HIV sero-discordant status among couples. Many men and women who are in relationships with a partner who is HIV positive do not know their own HIV status let alone their partner's [21]. In settings with a generalised HIV epidemic, research shows that in the context of sero-discordant relationships women

recommended to initiate treatment [24]. The utilisation of ARV to prevent HIV transmission thus transformed the field of comprehensive care for couples, particularly when the existing foundation was primarily the promotion of condom use. In an analysis conducted by Lasry et al. [25] who assessed the plausibility of a combination of strategies to reduce risk among sero-discordant couples. They established that ART initiation was the most protective strategy employed. To demonstrate the effectiveness of the use of ARVs in reducing the risk of HIV transmission Hallal et al. [26] cites the Partners in Prevention project, among various other studies in their systemic review. The study was conducted across seven African countries namely Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia. The sample comprised of 3400 sero-discordant couples who were followed for a period of 24 months. A total of 349 (10.0%) started on HAART. The findings of the study showed that there was substantial (92.0%) reduction of HIV risk transmission through the utilisation of HAART [27]. An emerging trend is to employ strategies in combination with ART to expand the possibilities of interventions for sero-discordant couples [26]. In a rural setting in KwaZulu-Natal, South Africa, Oldenburg et al. [28] estimated the effect of ART in reducing the acquisition of HIV in sero-discordant couples in a HIV-hyperendemic and resource constrained setting. In the study, ART was delivered through primary care clinics that were primarily staffed and led by nurses. The researchers found that ART is highly effective in reducing HIV acquisition in sero-discordant couples, this is despite the constrained resources in the public health system.

Achieving 90-90-90: A Focus on Sero-Discordant Couples

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35

A breakthrough for the extremely high infection rates in the SADC region is PrEP, where ARVs are administered to those individuals who are at risk of sexually acquiring the virus [29]. In the contexts of sero-discordant couples, PrEP is usually administered to the HIV-negative partner, before possible HIV exposure, which inadvertently reduces the risk of HIV acquisition [23]. In various forms PrEP has been tested (i.e. oral tablets, vaginal/rectal microbicides) or being developed as long-acting vaginal rings and intramuscular injectables [30]. In regard to oral PrEP, findings from the Partners PrEP Study showed that daily oral consumption of Tenofovir Disoproxil Fumarate/emtricitabine (TDF/FTC) reduced the acquisition of HIV-1 by 75.0% and HSV-2 by 33.0% in heterosexual sero-discordant couples from Uganda and Kenya [26, 31]. Two PrEP trials, namely the FemPrEP and Vaginal and Oral Interventions to Control the Epidemic (VOICE), were stopped prematurely due to the futility associated with poor adherence [29]. An active arm of the VOICE trial also established no prevention benefit for

In regard to vaginal gels, the CAPRISA 004 study assessed the effectiveness and safety of 1.0% Tenofovir gel for the prevention of HIV infection in among 889 women (aged 18–40 years, who were sexually active with a sero negative status) from urban and rural KwaZulu-Natal [31, 32]. The researchers investigated the reduction of HIV incidence against varying degrees of adherence. The findings of the study demonstrated that HIV incidence reduction was 54.0% for high adherence (gel adherence >80%), the HIV incidence was 38.0% and 28.0% lower for intermediate adherence (gel adherence 50–80%) and low adherence (gel adherence <50%) respectively. Overall, the HIV infection was reduced with Tenofovir gel at an estimated 39.0%.

*4.1.2.2. Pre-exposure prophylaxis (PrEP) for the HIV-negative partner*

oral TDF/FTC owing to poor levels of adherence [29].

**Figure 3.** Prevention strategies to reduce the risk of HIV transmission for sero-discordant couples.

are especially more vulnerable to contracting the virus, due to their biological susceptibility as well as the infidelity of men [21]. A study conducted in a rural setting within South Africa, however found that HIV transmission was high among migrant men as well as migrant women returning to their partners. This finding suggest that there is a need to reconsider the premise that HIV transmission within stable relationships is attributed to extra marital sexual activity by men.

With this being said, HIV counselling and testing has mainly been individual based and sexspecific. In regard to individual based prevention strategies, Jones et al. [22] implemented a couples HIV risk reduction intervention (called Partner Project) that included HIV Counselling and Testing program in 6 urban community health clinics in Lusaka, Zambia. The researchers found that the use sexual barrier indicators was achieved among the intervention group. The results also showed that there was a reduction in intimate partner violence (IPV) for the entire sample. IPV commonly inhibits discussions among partners regarding HIV testing, sero-status disclosure and condom use. Hence there should be an essential component of HIV prevention services that also target the reduction of IPV.

#### *4.1.2. Treatment as prevention*

In the contexts of sero-discordant couples, two broad prevention strategies with ARVs can be considered. Namely: antiretroviral treatment (ART) for the HIV-positive partner and preexposure prophylaxis (PrEP) for the HIV-negative partner.

#### *4.1.2.1. Antiretroviral treatment (ART) for the HIV-positive partner*

The WHO HIV treatment guidelines [20, 23] recommend initiation of lifelong ART for individuals with a CD4 counts of 350/mm3 or lower. More recently, the WHO guidelines in 2013 recommended ART for all patients regardless of their CD4 count. Furthermore, for those who are in relationships with an HIV negative partner, the discordant partner is also recommended to initiate treatment [24]. The utilisation of ARV to prevent HIV transmission thus transformed the field of comprehensive care for couples, particularly when the existing foundation was primarily the promotion of condom use. In an analysis conducted by Lasry et al. [25] who assessed the plausibility of a combination of strategies to reduce risk among sero-discordant couples. They established that ART initiation was the most protective strategy employed. To demonstrate the effectiveness of the use of ARVs in reducing the risk of HIV transmission Hallal et al. [26] cites the Partners in Prevention project, among various other studies in their systemic review. The study was conducted across seven African countries namely Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia. The sample comprised of 3400 sero-discordant couples who were followed for a period of 24 months. A total of 349 (10.0%) started on HAART. The findings of the study showed that there was substantial (92.0%) reduction of HIV risk transmission through the utilisation of HAART [27]. An emerging trend is to employ strategies in combination with ART to expand the possibilities of interventions for sero-discordant couples [26]. In a rural setting in KwaZulu-Natal, South Africa, Oldenburg et al. [28] estimated the effect of ART in reducing the acquisition of HIV in sero-discordant couples in a HIV-hyperendemic and resource constrained setting. In the study, ART was delivered through primary care clinics that were primarily staffed and led by nurses. The researchers found that ART is highly effective in reducing HIV acquisition in sero-discordant couples, this is despite the constrained resources in the public health system.

#### *4.1.2.2. Pre-exposure prophylaxis (PrEP) for the HIV-negative partner*

are especially more vulnerable to contracting the virus, due to their biological susceptibility as well as the infidelity of men [21]. A study conducted in a rural setting within South Africa, however found that HIV transmission was high among migrant men as well as migrant women returning to their partners. This finding suggest that there is a need to reconsider the premise that HIV transmission within stable relationships is attributed to extra marital sexual

**Figure 3.** Prevention strategies to reduce the risk of HIV transmission for sero-discordant couples.

With this being said, HIV counselling and testing has mainly been individual based and sexspecific. In regard to individual based prevention strategies, Jones et al. [22] implemented a couples HIV risk reduction intervention (called Partner Project) that included HIV Counselling and Testing program in 6 urban community health clinics in Lusaka, Zambia. The researchers found that the use sexual barrier indicators was achieved among the intervention group. The results also showed that there was a reduction in intimate partner violence (IPV) for the entire sample. IPV commonly inhibits discussions among partners regarding HIV testing, sero-status disclosure and condom use. Hence there should be an essential component of HIV

In the contexts of sero-discordant couples, two broad prevention strategies with ARVs can be considered. Namely: antiretroviral treatment (ART) for the HIV-positive partner and pre-

The WHO HIV treatment guidelines [20, 23] recommend initiation of lifelong ART for

in 2013 recommended ART for all patients regardless of their CD4 count. Furthermore, for those who are in relationships with an HIV negative partner, the discordant partner is also

or lower. More recently, the WHO guidelines

prevention services that also target the reduction of IPV.

exposure prophylaxis (PrEP) for the HIV-negative partner.

individuals with a CD4 counts of 350/mm3

*4.1.2.1. Antiretroviral treatment (ART) for the HIV-positive partner*

activity by men.

34 Advances in HIV and AIDS Control

*4.1.2. Treatment as prevention*

A breakthrough for the extremely high infection rates in the SADC region is PrEP, where ARVs are administered to those individuals who are at risk of sexually acquiring the virus [29]. In the contexts of sero-discordant couples, PrEP is usually administered to the HIV-negative partner, before possible HIV exposure, which inadvertently reduces the risk of HIV acquisition [23]. In various forms PrEP has been tested (i.e. oral tablets, vaginal/rectal microbicides) or being developed as long-acting vaginal rings and intramuscular injectables [30]. In regard to oral PrEP, findings from the Partners PrEP Study showed that daily oral consumption of Tenofovir Disoproxil Fumarate/emtricitabine (TDF/FTC) reduced the acquisition of HIV-1 by 75.0% and HSV-2 by 33.0% in heterosexual sero-discordant couples from Uganda and Kenya [26, 31]. Two PrEP trials, namely the FemPrEP and Vaginal and Oral Interventions to Control the Epidemic (VOICE), were stopped prematurely due to the futility associated with poor adherence [29]. An active arm of the VOICE trial also established no prevention benefit for oral TDF/FTC owing to poor levels of adherence [29].

In regard to vaginal gels, the CAPRISA 004 study assessed the effectiveness and safety of 1.0% Tenofovir gel for the prevention of HIV infection in among 889 women (aged 18–40 years, who were sexually active with a sero negative status) from urban and rural KwaZulu-Natal [31, 32]. The researchers investigated the reduction of HIV incidence against varying degrees of adherence. The findings of the study demonstrated that HIV incidence reduction was 54.0% for high adherence (gel adherence >80%), the HIV incidence was 38.0% and 28.0% lower for intermediate adherence (gel adherence 50–80%) and low adherence (gel adherence <50%) respectively. Overall, the HIV infection was reduced with Tenofovir gel at an estimated 39.0%.

#### *4.1.3. Tailor-made sexual health services*

#### *4.1.3.1. Voluntary medical male circumcision (VMMC) for HIV-negative male partners*

VMMC has been recommended by PEPFAR and WHO, as an HIV prevention method to reduce the risk of HIV acquisition in generalised epidemics [30]. Evidence from South African, population-based data, demonstrates that there were lower HIV prevalence and incidence (55.0 and 65.0% lower, respectively) among circumcised men compared to uncircumcised men [29, 32]. Voluntary medical male circumcision is recommended, within heterosexual sero-discordant couples in the case where the male is the HIV-negative partner [31]. It is an excellent HIV prevention method, because it offers lifelong partial protection against femaleto-male sexual transmission of HIV. However, it is not recommended for HIV-positive males within heterosexual relationships or men who have sex with men [31]. To help increase coverage of VMMC, WHO recommended that all HIV-negative men in sero-discordant or concordant negative couples be routinely counselled about and linked to VMMC services [30].

*4.1.3.2. Family planning*

can offer insights [36, 38, 39].

**discordant couples**

effort to reach the 90-90-90 treatment goals.

Many sero-discordant couples have high fertility and both (infected and uninfected) partners often report desires of having children with their partner [36]. Pregnancy is a time of heightened risk of sexual transmission and acquisition of HIV. Technologically advanced options for conception for sero-discordant couples include intrauterine or intravaginal insemination (of semen during the fertile period). Vaginal insemination is regarded as the safer method of conception to circumvent the sexual transmission of HIV [37]. However, it may not be accessible or affordable to all, especially in low to middle income countries [36, 39]. As such preconception services for PLHIV and their partners are prudent, and should be part and parcel of the care package they receive. The purpose of preconception care and counselling (PCC) for PLHIV is to ensure that both partners are optimally healthy, prior to pregnancy, and that the risk of HIV transmission to the partner (sexual transmission) and child (through pregnancy, delivery or breastfeeding) are reduced [38]. Options for safer conception, that are less reliant on technology, for sero-discordant couples include ART for the positive partner, timed unprotected intercourse, and PrEP for the uninfected male partner. ART literature shows that safe conception may be feasible when the infected partner is virally suppressed and on ART. While fully suppressive ART use may significantly reduce the chance of sexual transmission, sexual HIV transmission may still occur [36, 37]. Limited and timed unprotected sex and –natural conception for HIV sero-discordant couples involves limited and timed unprotected sexual intercourse during the fertile periods. Women are advised to track their menstrual and ovulation cycles. Couples are encouraged to minimise their sexual encounters to the fertile period to decrease the number of

Achieving 90-90-90: A Focus on Sero-Discordant Couples

http://dx.doi.org/10.5772/intechopen.78313

37

unprotected sexual encounters while maximising their chance of conception [35–37].

**5. Barrier and facilitators to achieving 90-90-90 among sero-**

Periconception PrEP—is an option for the HIV negative partner. The benefits for the periconception PrEP is higher adherence and lower costs due to the shorter duration of utilisation. It is important to establish whether periconception PrEP regimen will help lower the risk of couples who have decided to conceive despite known risks of transmission to partner and baby. While there are no trials with a particular focus on the risk of HIV transmission among sero-discordant complies during conception, but data drawn from the safety and efficacy of PrEP in future clinical trials among heterosexuals couples and trials testing drugs for PMTCT

The possibility of sero-discordant relationships are becoming more common, given the improved quality of life and higher life expectancy for people living with HIV [26]. It is therefore imperative to expand HIV prevention efforts that target sero-discordant couples in the

In regard to HIV testing and counselling, evidence shows that many of the prevention strategies to reduce the risk of HIV transmission in couples are individual as opposed to couples

Several research confirming the protective effect of VMMC against HIV infection have been published [30, 31, 33–35]. Baeten et al. [35] conducted an observational study with 1096 African HIV-1 sero-discordant couples in which the index partner (HIV-1 seropositive partner) was male. The sample was drawn from 7 Southern African (Gaborone, Botswana; Cape Town, Orange Farm, and Soweto, South Africa; Kitwe, Lusaka, and Ndola, Zambia) and 7 eastern African Africa (Eldoret, Kisumu, Nairobi and Thika, Kenya; Kigali, Rwanda; Moshi, Tanzania; Kampala, Uganda) sites. The results showed a non-statistically significant decrease in the risk of HIV-1 transmission for circumcised HIV-1 infected men to their female partners in comparison to couples with uncircumcised HIV-1 infected men. This finding adds to a limited body of data relating circumcision status in HIV-1 infected men to the risk of maleto-female HIV-1 transmission, data which may be helpful for programmes working to scaleup male circumcision for HIV-1 prevention. Randomised trials from Kenya, South Africa, and Uganda demonstrated that male circumcision reduces a man's risk of acquiring HIV-1 by approximately 60.0%.

Auvert et al. [33] conducted an experimental trial to test the efficacy of Medical circumcision (MC) as a protecting factor against HIV infection among men. The study was the first randomised control trial, in South Africa, that aimed to test the impact of MC on health. The findings demonstrated MC offers a substantially high level of protection for men against acquiring HIV infection, this protection may be seen as effectiveness as what a vaccine of high efficacy would achieve [33]. Furthermore, Auvert et al. [34] continued to do research on medical male circumcision. They implemented the Bophelo Pele community-based HIV campaign (Orange Farm, South Africa). The campaign included the roll-out of free VMMC. A cross-sectional survey was administered with men aged 15–49 years. The results of the survey suggest that the roll-out of VMMC was associated with a reduction in the incidence and prevalence of HIV among circumcised men as compared to uncircumcised men. Furthermore, the findings also provide an argument that the uptake of VMMC is plausible and may become acceptable in communities that were traditionally non-circumcising communities in South Africa and sub-Saharan Africa [34].

#### *4.1.3.2. Family planning*

*4.1.3. Tailor-made sexual health services*

36 Advances in HIV and AIDS Control

approximately 60.0%.

Africa and sub-Saharan Africa [34].

*4.1.3.1. Voluntary medical male circumcision (VMMC) for HIV-negative male partners*

VMMC has been recommended by PEPFAR and WHO, as an HIV prevention method to reduce the risk of HIV acquisition in generalised epidemics [30]. Evidence from South African, population-based data, demonstrates that there were lower HIV prevalence and incidence (55.0 and 65.0% lower, respectively) among circumcised men compared to uncircumcised men [29, 32]. Voluntary medical male circumcision is recommended, within heterosexual sero-discordant couples in the case where the male is the HIV-negative partner [31]. It is an excellent HIV prevention method, because it offers lifelong partial protection against femaleto-male sexual transmission of HIV. However, it is not recommended for HIV-positive males within heterosexual relationships or men who have sex with men [31]. To help increase coverage of VMMC, WHO recommended that all HIV-negative men in sero-discordant or concordant negative couples be routinely counselled about and linked to VMMC services [30].

Several research confirming the protective effect of VMMC against HIV infection have been published [30, 31, 33–35]. Baeten et al. [35] conducted an observational study with 1096 African HIV-1 sero-discordant couples in which the index partner (HIV-1 seropositive partner) was male. The sample was drawn from 7 Southern African (Gaborone, Botswana; Cape Town, Orange Farm, and Soweto, South Africa; Kitwe, Lusaka, and Ndola, Zambia) and 7 eastern African Africa (Eldoret, Kisumu, Nairobi and Thika, Kenya; Kigali, Rwanda; Moshi, Tanzania; Kampala, Uganda) sites. The results showed a non-statistically significant decrease in the risk of HIV-1 transmission for circumcised HIV-1 infected men to their female partners in comparison to couples with uncircumcised HIV-1 infected men. This finding adds to a limited body of data relating circumcision status in HIV-1 infected men to the risk of maleto-female HIV-1 transmission, data which may be helpful for programmes working to scaleup male circumcision for HIV-1 prevention. Randomised trials from Kenya, South Africa, and Uganda demonstrated that male circumcision reduces a man's risk of acquiring HIV-1 by

Auvert et al. [33] conducted an experimental trial to test the efficacy of Medical circumcision (MC) as a protecting factor against HIV infection among men. The study was the first randomised control trial, in South Africa, that aimed to test the impact of MC on health. The findings demonstrated MC offers a substantially high level of protection for men against acquiring HIV infection, this protection may be seen as effectiveness as what a vaccine of high efficacy would achieve [33]. Furthermore, Auvert et al. [34] continued to do research on medical male circumcision. They implemented the Bophelo Pele community-based HIV campaign (Orange Farm, South Africa). The campaign included the roll-out of free VMMC. A cross-sectional survey was administered with men aged 15–49 years. The results of the survey suggest that the roll-out of VMMC was associated with a reduction in the incidence and prevalence of HIV among circumcised men as compared to uncircumcised men. Furthermore, the findings also provide an argument that the uptake of VMMC is plausible and may become acceptable in communities that were traditionally non-circumcising communities in South Many sero-discordant couples have high fertility and both (infected and uninfected) partners often report desires of having children with their partner [36]. Pregnancy is a time of heightened risk of sexual transmission and acquisition of HIV. Technologically advanced options for conception for sero-discordant couples include intrauterine or intravaginal insemination (of semen during the fertile period). Vaginal insemination is regarded as the safer method of conception to circumvent the sexual transmission of HIV [37]. However, it may not be accessible or affordable to all, especially in low to middle income countries [36, 39]. As such preconception services for PLHIV and their partners are prudent, and should be part and parcel of the care package they receive. The purpose of preconception care and counselling (PCC) for PLHIV is to ensure that both partners are optimally healthy, prior to pregnancy, and that the risk of HIV transmission to the partner (sexual transmission) and child (through pregnancy, delivery or breastfeeding) are reduced [38]. Options for safer conception, that are less reliant on technology, for sero-discordant couples include ART for the positive partner, timed unprotected intercourse, and PrEP for the uninfected male partner. ART literature shows that safe conception may be feasible when the infected partner is virally suppressed and on ART. While fully suppressive ART use may significantly reduce the chance of sexual transmission, sexual HIV transmission may still occur [36, 37]. Limited and timed unprotected sex and –natural conception for HIV sero-discordant couples involves limited and timed unprotected sexual intercourse during the fertile periods. Women are advised to track their menstrual and ovulation cycles. Couples are encouraged to minimise their sexual encounters to the fertile period to decrease the number of unprotected sexual encounters while maximising their chance of conception [35–37].

Periconception PrEP—is an option for the HIV negative partner. The benefits for the periconception PrEP is higher adherence and lower costs due to the shorter duration of utilisation. It is important to establish whether periconception PrEP regimen will help lower the risk of couples who have decided to conceive despite known risks of transmission to partner and baby. While there are no trials with a particular focus on the risk of HIV transmission among sero-discordant complies during conception, but data drawn from the safety and efficacy of PrEP in future clinical trials among heterosexuals couples and trials testing drugs for PMTCT can offer insights [36, 38, 39].
