Adherence and Support
"I'm 18 years, you are telling me drugs for life?" --Woman living with HIV in Uganda (Hsieh, 2013: 11)Treatment adherence is necessary to continually suppress the virus. Adherence to ART leads to better virological outcomes, prevents disease progression and improves survival (Nachega et al., 2010a; Nachega et al., 2010c). Conversely, inadequate adherence leads to drug resistance, which can then be transmitted to others (Simon et al., 2010) and lead to disease progression and death (Nachega et al., 2010c). "Preventing adherence-related treatment failure is especially important in resource-limited settings wherein second-line therapy is up to 17 times more expensive than first line therapy and often unavailable" (MSF, 2010 cited in Pop-Eleches et al., 2011: 831). WHO 2013 guidelines also note that the first ART regimen offers the best opportunity for effective virological suppression and requires that medication be taken exactly as prescribed (WHO, 2013: 89). Simple, safer, once-daily, single-pills for first line therapy are now the standard of care (WHO, 2013) and multiple pill regimens for first line therapy are being phased out.
Treatment has been successfully administered with good adherence in many populations and groups, including among sex workers (Huet et al., 2011: para 21); and people who inject drugs (Werb et al., 2010; Malta et al., 2010; Wisaksana et al., 2010; Wood et al., 2008; Mimiaga et al., 2010). However, while HIV prevalence globally among female sex workers is 12% (36.9% in Sub-Saharan Africa) (Baral et al., 2012), ART use among female sex workers living with HIV is only 38% (Mountain et al., 2014). Female sex workers are 12 times more likely to be living with HIV than women in the general population (UNAIDS, 2014a). More studies are needed to elucidate and overcome barriers to treatment and adherence for sex workers, such as discrimination by providers (Mountain et al., 2014). [See also Prevention for Key Affected Populations] Studies in Canada and France among people who use drugs found that those who were prescribed opioid agonist therapy had higher rates of adherence to antiretroviral therapy and longer-term virological success (Uhlmann et al., 2010; Roux et al., 2009). [For information on interactions between antiretrovirals and opioid agonist therapy, please refer to (Bruce et al., 2010; Altice et al., 2010: 68-69).]
Continuous Monitoring is Needed to Ensure Viral Suppression
HIV care and treatment programs have largely been evaluated by the numbers enrolled in care (McNairy and El-Sadr, 2012). Monitoring adherence requires multiple approaches including viral load monitoring, pill counts and measurements and self-reports, among others. In 2013, the World Health Organization recommended the use of routine viral load measurement as the preferred way of monitoring treatment outcomes (WHO, 2013) beyond merely counting the number of people started on ART (Collins, 2014). Also in 2013, UNAIDS launched the 90/90/90 global treatment campaign that, in addition to 90% of people living with HIV knowing their status and 90% of all people diagnosed with HIV receiving sustained ART, envisions that 90% of all people receiving ART will have viral suppression by 2020 (UNAIDS, 2014b). While these goals may be ambitious, some countries are on course to achieve the viral suppression target: in a nationally representative survey, 82.3% of patients on ART in Rwanda were found to be virologically suppressed (Binagwaho et al., 2014). New HIV infections in Rwanda fell 60.3% and AIDS-related mortality dropped 82.1% between 2000 and 2012, which may be a result of high rates of virological suppression among those living with HIV (Binagwaho et al., 2014). But there is still a long way to go: UNAIDS estimates that in sub-Saharan Africa, only 29% of people living with HIV are virally suppressed (UNAIDS, 2014b).
A study in Canada with 1,305 patients confirmed that once viral suppression was initially achieved, adherence of at least 95% or greater was needed to maintain viral suppression: after adjusting for duration of suppression, individuals with adherence less than 95% were 11% more likely to rebound, i.e., experience an HIV viral load increase, than those who were adherent 95% or more of the time (Lima et al., 2010). However, the adherence requirement of over 95% is based on the use of unboosted protease inhibitors (PI), which are less available in resource-limited settings (Chung et al., 2011). In resource-limited settings, most antiretroviral regimens contain non-nucleoside reverse transcriptase inhibitors (NNRTI), such as nevirapine or efavirenz, which have long half-lives and may remain in the patients body for weeks. Thus, antiretroviral resistance may not occur in patients on NNRTI regimens until their adherence drops below 80% (Cressey et al., 2005 cited in Chung et al., 2011). Still, treatment adherence remains critical to viral suppression and improved survival.
Addressing Barriers to Treatment Adherence is Critical to Maintaining High Levels of Retention
"I feared my husband would know, and if he knew, he was going to divorce me. Where can I go if I get divorced? Who will look after my children? I just said to myself that it is better that I stop medication so that I can protect my marriage, and so that my children can have a future." --Woman living with HIV who stopped treatment, Zambia (Musheke et al., 2012: 4)Improved reporting is needed to assess why people discontinue therapy and how to keep patients adherent to antiretroviral therapy (WHO et al., 2011b). A systematic review of 84 studies examining barriers to treatment adherence found fear of disclosure, forgetfulness, a lack of understanding of treatment benefits, complicated regimens, and being away from medications were consistent barriers to adherence in developed and developing nations. More common to developing country settings were issues of access, including financial constraints and a disruption in access to medications (Mills et al., 2006: 18). Clearly, when patients have to pay for ARVs in resource-limited settings in a context of poverty, access and adherence will be negatively affected (Lal et al., 2010; Ruanjahn et al., 2010). Having to walk long distances to access services is another factor in one study in Zambia, over half of patients had to walk for more than one hour to access services (Sasaki et al., 2012). WHO reports that of 118 countries reporting, 38% reported at least one or more ARV stock outs in health facilities during 2009 (WHO, 2010 cited in Atun and Bataringaya, 2011; WHO et al., 2011b), which can make adherence unachievable for patients. To address the issue of stock-outs, WHO has developed key indicators to monitor the performance of supply chain management systems (WHO, 2011e).
In 2009, 18% of people who started antiretroviral therapy in low- and middle-income countries were no longer in care within 12 months (UNAIDS, 2011a). Average retention at 12 months after initiating antiretroviral therapy was 67% at 60 months, with 46 countries reporting (WHO et al., 2011b). Globally, retention at 12 months is similar among women and men (WHO et al., 2011b). In a recent study of 4,147 patients in 17 facilities in Tanzania, Uganda and Zambia, retention ranges from 25.8% to 90.4% at year four (Koole et al., 2014), showing that some sites are in need of critical improvements to improve retention to care. Additional research is needed to understand why adherence interventions are effective in some settings yet not effective in other settings (Chaiyachati et al., 2014).
There Are Gender Differences in Treatment Adherence
"When I disclosed to my husband, He refused to accept. Whenever he finds my ARVs, he throws them in the latrine." --Woman living with HIV who is a member of Women Fighting AIDS, Kenya (Machera, 2009: 19)For the most part, men and women have similar adherence rates, though a few studies have found higher rates of non-adherence in women (Puskas et al., 2011). There are, however, gender differences in predictors of adherence. Women may need family support, including redistribution of household responsibilities, to enable them to adhere to treatment. Even if drugs are free or subsidized, women may not be able to afford the time or money required to travel to a clinic. A qualitative study of women living with HIV in Colombia found that women prioritized the needs of their HIV-positive children over their own adherence needs (Arrivillaga et al., 2011). Women in Malawi and Uganda also reported challenges in managing their own adherence as well as that of their children (Hsieh, 2013). Some women sold their ARVs to survive financially (Arrivillaga et al., 2011). Women may also have difficulty navigating treatment when it conflicts with other activities for survival. Sex workers, in particular, face difficulties in adherence in large part due to stigma and discrimination. [See Strengthening the Enabling Environment and Female Sex Workers] One South African sex worker points out the struggles she faces: "If you don't pay off the police, they take you to jail...you can't take antiretroviral drugs or any medication you need" (Arnott and Crago, 2009: 10). Women sex workers in Vietnam reported that they were not allowed to join networks of people living with HIV who gained access to valuable support and information services because they were seen as "social evils" rather than "innocent wives getting the disease from their husband" (Nguyen et al., 2013: 218).
Side effects can also deter women from adhering to treatment plans. Some medications cause a redistribution of body fat resulting, for example, in a large belly, or a collection of fat at the base of the neck, or loss of fat from the cheeks (Mbonye et al., 2013; Han et al., 2011; Elliott et al., 2011). Women reported problems with adherence due to how ARVs changed their appearance with bodily changes creating visibility of their HIV-positive serostatus and consequent stigma. Women may also be more adversely affected by the common side effects of ARVs that result in anemia. Yet a food assistance program in Mozambique did not increase adherence compared to those with no food assistance (Posse et al., 2013). A study of quality of life among people living with HIV in Cuba found that women reported higher levels of pain compared to men, and that pain interfered more in women's lives than in men's lives, and that overall, women did not enjoy the same health-related quality of life as men (Aragones-Lopez et al., 2012). In some countries, such as Vietnam, men (1,016 patients, 63.8% male) reported better quality of life on antiretroviral therapy than did women, as women cared for their husbands, some of whom injected drugs (Tran, 2012).
"It involves being shouted upon like a child, don't you see, no respect at all." --Ugandan man reporting being scolded by nurses (Siu et al., 2013: 49)However, it is also clear that men face particular challenges in accessing and adhering to HIV treatment, as men's ideal sense of masculinity may be threatened by disclosing their status and seeking treatment. Being physically strong, capable of hard work and having children were also seen as signs of masculine identity, which were threatened by being labeled HIV-positive. Furthermore, men often perceive health services as spaces for women and children rather than for them. Services can seem "male-unfriendly" (Skovdal et al., 2011d: 2). A study from South Africa found that men's adherence was challenged by factors related to an enabling environment, such as conditions of employment, with problems getting time away from work for clinic visits or loss of income due to waiting in lines at clinics (Maskew et al., 2013).
Support groups and counseling for men may also be beneficial (Hsieh, 2013). Focus group discussions with men living with HIV on treatment who had disclosed to their partners in South Africa found that men wanted to access male-only support groups at clinics where they collect their medication with guarantees that their HIV status would not be disclosed outside of the support group setting. Despite the fact that support groups were available four times per week, men did not know of these support groups (Madiba and Canti-Sigaqa, 2012). Yet in a study in Uganda, men who were recipients of support, such as expenses for childrens education, or given livelihood options, such as goats, were more adherent than men without this support. Treatment may be undertaken by some men to regain health, self-worth, ability to work and provide for their families as a sign of their masculinity (Siu et al., 2012; Siu et al., 2013).
Nondisclosure Contributes to Adherence Difficulties
Disclosure can have both negative and positive consequences. Disclosure has the potential to lead to much needed support or it may lead to stigma, discrimination, abandonment or violence (Sasaki et al., 2012; Amanyeiwe et al., 2014). A study in Uganda found that internalized stigma was correlated with lack of disclosure, and suggested that stigma reduction efforts are key to increasing disclosure (Tsai et al., 2013). [See also Reducing Stigma and Discrimination] A global review of stigma and adherence found that in some studies, disclosure was correlated with increased adherence, while in other studies, disclosure did not result in increased adherence. Where stigma was great, treatment was interrupted in order to conceal an HIV-positive status (Katz et al., 2013). A study in Botswana found that nondisclosure of positive HIV-status to a sexual partner was predictive of poor adherence rates (Do et al., 2010).
"I lost my marriage when I told my husband my status...so I did not tell my boss...Instead, I decided to stop going to the clinic so that she does not know my status." --Woman living with HIV who stopped treatment, Zambia (Musheke et al., 2012: 5)A woman may not disclose her status to her husband for fear of violence. A global survey of 2,035 adults living with HIV found that 17% of patients in long-term relationships had not disclosed their serostatus to their sexual partner. Patients feared the impact of disclosure on their relationships and their employment (Nachega et al., 2012). Studies of interventions to facilitate disclosure are lacking (Reda and Biadgilign, 2012). In some studies, men living with HIV reported caregiving and support from their sexual partner, however, women reported that disclosure resulted in a narrative of "neglect and violence (at times in life-and-death terms), often culminating in estrangement or divorce after the disclosure of their HIV-positive status to their male partners" (Schneider et al., 2012: 823). Some women in Uganda and Malawi feared violence or being ejected from their homes if they disclosed their positive serostatus (Hsieh, 2013; Omunakwe et al., 2014; Katz et al., 2013). [See also Transforming Gender Norms and Addressing Violence Against Women]
Improving Treatment Adherence Requires Counseling, Empowerment to Overcome Barriers and Reduce Loss to Follow Up
Treatment programs must assess who gains access to treatment, how, and if it is accompanied by care and support. Does the program address adherence? Do patients receive adherence support? Do patients receive good quality counseling? Are patients satisfied with their quality of care? Have patients received proper information on medications and dosage? (Gruskin et al., 2007a). Programs should also promote treatment literacy so that all people know that AIDS cannot be cured but that ARV treatment can prolong life, with improved quality of life (IOM, 2013). For those on ARV therapy, treatment literacy is vital to understanding the importance of adherence. A survey in Togo found that patients who had good knowledge of the number of tablets per dose, the name of daily intakes and the times of drug intake had better adherence (Potchoo et al., 2010). Another survey in Cuba found that motivation was key (Beng et al., 2011).
"It is difficult for me to go to the doctor. I have to ask permission to leave work. This is not easy because if told (my bosses) that I have AIDS, they would fire me. Nobody ever offers to take care of the kids." --Woman living with HIV in Colombia (Arrivillaga et al., 2011: 180)Adherence may be best improved by addressing multiple levels simultaneously: with health providers that support families living with HIV, as well as community wide stigma reduction efforts (Katz et al., 2013). Ensuring that people are not lost to follow up is critical for maintaining treatment adherence. In some studies, men were more likely to be lost to follow up once on ART (Charurat et al., 2010; Tweya et al., 2010).
While there is little data demonstrating what works specifically for women in improving treatment adherence, there are some interventions that have been shown to work for both men and women such as provision of counseling, treatment support and treatment literacy. Counseling support by HIV-positive peers has been found to also be effective in improving treatment adherence in Thailand, through a model developed by the Thai Network of People With HIV/AIDS (TNP+). In Haiti, Rwanda and Lesotho, the Partners in Health's "accompaniment" model, which includes daily home visits by community health workers, free clinic visits, nutritional support, transportation to clinics and preferential hiring of people living with HIV has also been found effective (Ford et al., 2009a). [See also Promoting Women’s Leadership] A study of MSM in the United States found when sexual partners regard themselves as a collective unit, those partners living with HIV had higher rates of viral suppression, suggesting that incorporating relationship dynamics into counseling is important (Gamarel et al., 2014). For migrant workers, mobile HIV services with longer lasting supplies of ARVs is a promising model for the many migrant populations who need reliable HIV treatment supplies (Lynch et al., 2012).
WHO recommends a combination of programmatic and individual level interventions to support adherence. Programmatic interventions to adherence include use of fixed dose treatment regimens, minimizing costs related to ART and ensuring commodity security. Individual level interventions include use of mobile phone reminders (Lester et al., 2010), peer support mechanisms such as support groups, nutrition support and management of mental health conditions and drug abuse (WHO, 2013).
The World Health Organization also provides guidance on decentralization of treatment and task shifting that may increase access to ART and impact both retention and adherence to ART (WHO, 2013). Some progress is being made on decentralization: in 23 countries where Mdecins sans Frontires is working, ART has been made available at more than 40% of public facilities in four countries and more than 20% in more than eight countries, while 13 out of 16 countries now allow lay counselors to provide ART adherence counseling (Lynch et al., 2012). Additional strategies such as the use of health workers to monitor adherence, task shifting and paid patient advocates (Igumbor et al., 2011; Braitstein et al., 2012) have all shown to increase adherence but are outside the scope of this compendium.
"These pills mean life to me, so if they were no longer accessible I would die." --Patient (Gilbert and Walker, 2009: 1126)New technologies to facilitate adherence are also being developed (Haberer et al., 2010) such as the use of hand-held personal digital assistants to track and assess patients (Selke et al., 2010), lab results linked to mobile phone technology and connecting peers in an area. Physicians are poor predictors of whether a patient will be adherent (Walshe et al., 2010) and pill counts, viral load, and other externally validated ways should be used to measure adherence. These practices and tools are useful for both men and women. Although most adherence interventions address both men and women, further research is needed regarding the best ways to overcome a number treatment adherence barriers specific to women such as fear of disclosure, stigma, violence, body image issues related to medication side effects, among others.