Adherence and Support
Successful treatment requires daily dosing for the remainder of the patient's life (Dieffenbach and Fauci, 2011). Treatment adherence is necessary to continually suppress the virus. "Adherence to ART is known to predict better virological outcomes, prevent antiretroviral drug resistance and disease progression and improve survival" (Nachega et al., 2010a: 18). On the other hand, inadequate adherence enables the virus to develop resistance, which can then be transmitted to others (Simon et al., 2010) and lead to disease progression and death (Nachega et al., 2010c). Loss of viral suppression may begin as early as 48 hours after a lapse in adherence, and a 15 day interruption confers a 50% chance of virologic failure with some treatment regimens (Parienti et al., 2008 cited in Haberer et al., 2010). "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).
"I know the reasons of why I have to take this medicine. I know the goals. I have a will to live, so this makes me continue to take the medicines on time." HIV-positive woman, Thailand (Rongkavilit et al., 2010: 790)
A recent study in Canada with 1,305 patients confirmed that once viral suppression was initially achieved, adherence of at least 95% or greater was needed: 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, adherence requirement of over 95% are 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.
Treatment has been successfully administered with good adherence in many populations and groups, including among sex workers (Huet et al., 2011; Para 21; Low et al., 2012); 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). Studies in Canada and France found that and 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. and Altice et al. (Bruce et al., 2010; Altice et al., 2010: 68-69).]
Greater adherence may even result in lower long-term health care costs: besides the good clinical benefits from ART adherence, with better survival, greater adherence was associated with decreased hospitalization costs in a South African study (Nachega et al., 2010a).
Addressing Barriers to Treatment Adherence is Critical to Maintaining High Levels of Retention
Improved reporting is needed to assess why people discontinue therapy and how to keep patients adherent to antiretroviral therapy (WHO et al., 2011b). 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, averting 84% of deaths in 50 reporting countries (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 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., 2011; Ruanjahn et al., 2010). Further, 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 some resource-limited settings, however, adults have achieved high levels of adherence (90% of patients achieved over 95% adherence) as measured by pharmacy pill counts (Campbell et al., 2010b).
There Are Gender Differences in Treatment Adherence
"... It is difficult for me to go to the doctor. I have to ask permission to leave work. This is not easy because if I 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)For the most part, men and women have similar adherence rates, and women are able to follow complicated regimens as well as men. But there are 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. 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. 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). 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 HIV status and seeking treatment in fear that they would be perceived as failing sons, husbands or breadwinners... The problem of 'male-unfriendly' services is not confined to the HIV/AIDS field... Hospitals are seen as spaces for women and children, not for men." Support groups and counseling for men may also be beneficial (Skovdal et al., 2011b: 2).
Other factors such as nondisclosure can contribute to reduced adherence. 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). A woman may not disclose her status to her husband for fear of violence. In a Nigerian study, men had superior adherence rates to women (Salami et al., 2010) and study authors hypothesized, "this may be related to sociocultural factors because our society is male dominated and disclosure of HIV status especially to an HIV-negative husband may come with dire consequences" (Salami et al., 2010: 193). [See alsoTransforming Gender Normsand Addressing Violence Against Women]
Restrictive diets and 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. "The regimens are often complicated, can require dietary restrictions and may lead to adverse effects," such as changes in body fat that can negatively impact body image (Mills et al., 2006: 2; Holstad et al., 2006).
Improving Treatment Adherence Requires Counseling, Empowerment to Overcome Barriers
"I started HIV medication in 2006. My husband does not know... He beats me up and locks me out of the house... I sleep under the tree until tomorrow. As a result of that, I miss doses sometimes." HIV-positive woman, Zambia (HRW, 2007: 1)
It is critical for treatment programs to assess not just how many people who need treatment gain access to treatment but who gains access, 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). Adherence is defined as "taking medication as prescribed, and therefore issues such as pharmacy stock-outs are out of the patients control" (Bangsberg, 2008). 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 (UNAIDS, 2005). For those on ARV therapy, treatment literacy is vital to understanding the importance of adherence. A survey in Togo found that patients who have good knowledge of the number of tablets per dose, the name of daily intakes and the times of drug intake have better adherence (Potchoo et al., 2010). Another survey in Cuba found that motivation was key (Beng et al., 2011).
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, including treatment support and literacy. A meta-analysis of 19 randomized controlled trials including 1,839 patients found that patients given one-on-one counseling by health providers, with a median of two sessions lasting 60 minutes each, resulted in patients being more than one and a half times more likely to achieve 95% adherence, compared to controls (Simoni et al., 2006 cited in Vergidis et al., 2009). An observation study of low-literacy and low-income patients in 2005 in Mozambique also found improved adherence among patients who received counseling from health care providers (Magnano San Lio et al., 2009). 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+), and in Haiti, Rwanda and Lesotho, supported by Partners in Healths "accompaniment" model, which includes daily home visits by community health workers, free clinic visits, nutritional support, transportation to clinics and preferential hiring of HIV-positive people (Ford et al., 2009a). [See also Promoting Women’s Leadership] Counseling plus home visits and community health worker involvement in a study with 13,391 patients in eight countries found a loss to follow up of only 1% to 5% compared to the 14% loss to follow up among those who received counseling only (Etienne et al., 2010 cited in Geng et al., 2010c). Additional strategies such as the use of health workers to monitor adherence, task shifting and paid patient advocates (Igumbor et al., 2011) have all shown to increase adherence but are outside the scope of this compendium.
Pill counts and pillbox organizers are low-technology empowerment tools that can increase adherence. Data obtained from an observational cohort of 245 people living with HIV from 1996 to 2000 in the United States showed that pillbox organizers were estimated to improve adherence by 4.1 to 4.5% and was associated with a decrease in viral load of .34-.37 log10 copies/mL and a 14.2% to 15.7% higher probability of achieving a viral load of greater than 400 copies/mL, with statistically significant effects. "Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy" (Peterson et al., 2007). Mobile phone technologies have also been successfully employed. Mobile phone ownership worldwide has grown to 4.1 billion in 2008 (International Telecommunications Union, 2009 cited in Pop-Eleches et al., 2011). Other 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).
One study in Thailand showed that simplifying treatment regimens is associated with adherence (Ruanjahn et al., 2010). A review of 22 articles from 2006 to 2008 with several thousand patients found that a pill burden of more versus less than 10 pills per day was associated with much higher odds of non-adherence than twice versus once daily dosing or small differences in the types of antiretroviral treatments in a regimen (Atkinson and Petrozzino, 2009). A meta-analysis of eleven randomized controlled trials found that better adherence was achieved among individuals who received a once daily regimen compared to individuals who received a twice daily regimen (Parienti et al., 2009). 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, however 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.