Sub-Saharan Africa has been devastated by the HIV pandemic, and in 2003 the World Health Organization (WHO) launched its 3 by 5 initiative to treat 3 million people with AIDS in developing countries by 2005 . Although high levels of adherence have been attained at several centers in Africa [2–4], critics have expressed concern regarding whether these levels of adherence can be sustained in large-scale national antiretroviral therapy (ART) programmes. Furthermore, little is known about obstacles to ART adherence in Africa . There is also apprehension that with access to ART individuals may increase risky sexual behaviors, as seen in certain developed country settings . We report an analysis of obstacles to treatment adherence and changes in sexual behavior in Rwandan adults taking ART.
The study took place at Projet San Francisco, a research clinic in Kigali, Rwanda, which has cared for HIV-positive individuals since 1986, and has been well described previously [7–10]. Study procedures were approved by the Research Ethics Committee in Kigali, Rwanda, and the Institutional Review Board of Emory University. Human research guidelines were followed, and informed consent was obtained from all participants. Generic antiretroviral drugs were provided free of charge to patients who met WHO and national guidelines as part of an ART programme initiated in 2003 with funding from the Global Fund for AIDS, Tuberculosis, and Malaria. Each patient at the clinic had undergone extensive ART counseling and had their medications administered by directly observed therapy for the initial 2 weeks to ensure that medication instructions were understood. Each patient was also required to have a support partner for assistance with medications. We have previously demonstrated a high level of adherence in this cohort, with 100% of patients achieving more than 95% adherence and an 81% reduction in mortality compared with historical controls . We interviewed five patients and one patient's spouse about obstacles to ART adherence to generate a questionnaire. We then administered this questionnaire to 71 patients on ART. All interviews and questionnaires were administered in Kinyarwandan, Rwanda's native language, by trained nurse counsellors. After each questionnaire patients were debriefed and counselled on any misconceptions that were identified.
The median age of participants surveyed was 40 years, and 65% were women. Over 71% of patients had received little formal education (primary school or less). Patients reported receiving ART for a median of 5 months at the time of the survey. Despite little formal education, over 92% of patients understood the following: HIV lowered the CD4 cell count; ART raised the CD4 cell count; ART medications needed to be taken for the rest of their lives even if they appeared to be healthy; and ART medications should never be missed. Notably, however, 81% were not aware that antiretroviral drugs could have serious side-effects that were not clinically obvious.
A summary of our findings regarding obstacles to adherence is presented in Table 1. A surprising obstacle to ART initiation for 76% of patients was the fear of developing too much appetite on ART but not having enough to eat. Fifty-six per cent of patients brought up this concern in response to an open-ended question without prompting. In contrast, other factors such as inconvenience to daily routine, drug toxicities, and acceptance of their HIV illness were concerns to only a minority of patients.
ART dramatically improved patients' socioeconomic status, with 87% regaining the ability to work at home or at a job. More than 40% reported sharing their HIV status with additional people after starting ART, and 82% were more willing to encourage other people to get tested for HIV. Conversely, there was no increase in risky sexual behavior since the initiation of ART. Among patients sexually active at ART initiation (n = 44), 52% reported having sex less frequently, and only 11% reported having sex more frequently. Furthermore, among patients still sexually active at the time of our survey (n = 35) safe sex practices did not worsen, with 26% reporting more frequent condom usage and only 3% reporting less frequent condom usage.
This study identified a unique and potentially major obstacle to adherence: the fear of developing too much appetite but not having enough to eat. As a low body mass index is associated with poor clinical outcomes even after ART initiation [12–14], nutritional supplementation as an adjunct to ART may improve both adherence and prognosis. In response to these concerns, we have been providing nutritional supplementation. In agreement with a study from South Africa , this study found that patients were less concerned about traditional barriers to adherence such as medication side-effects or disruptions to their daily routine. Our study also demonstrates that a sophisticated understanding of ART can be achieved with counselling in populations with little formal education.
Regarding concerns that access to ART will lead to risky sexual behavior, this study reassuringly found that despite a dramatic improvement in their socioeconomic lives, patients maintained safe sex behavior with condom usage. This finding suggests that the scale-up of ART in Africa will not compromise efforts to encourage condom usage to reduce HIV transmission, and has been confirmed in other settings in Africa  and worldwide .
A limitation of our study is that we interviewed a select group of patients that was well prepared for ART through the clinic's extensive counselling and requirement of a support partner. Other clinics in sub-Saharan Africa offering ART may not have resources for such intensive preparation. In addition, patients in this study had been on ART for only a short period of time, and future research is necessary to evaluate whether patients' enthusiasm for adhering to ART and maintaining safe sex behavior wane with time.
In conclusion, our findings support increasing and integrating nutritional supplementation into ART programmes to improve adherence and maximize the benefits of therapy.
The authors thank all the patients who participated in this study and the staff at Projet San Francisco who made this study possible.
Sponsorship: This study was made possible by funding from the International AIDS Vaccine Initiative, the Global Fund for AIDS, Tuberculosis, and Malaria, and the National Institutes of Health (NIMH R01 66767).
1. World Health Organization, Joint United Nations Programme on HIV/AIDS. Treating 3 million by 2005: making it happen: the WHO strategy
. Geneva: World Health Organization, Joint United Nations Programme on HIV/AIDS; 2003.
2. Laurent C, Ngom Gueye NF, Ndour CT, Gueye PM, Diouf M, Diakhate N, et al
. Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults. J Acquir Immune Defic Syndr 2005; 38:14–17.
3. Nachega JB, Stein DM, Lehman DA, Hlatshwayo D, Mothopeng R, Chaisson RE, Karstaedt AS. Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa. AIDS Res Hum Retroviruses 2004; 20:1053–1056.
4. Orrell C, Bangsberg DR, Badri M, Wood R. Adherence is not a barrier to successful antiretroviral therapy in South Africa. AIDS 2003; 17:1369–1375.
5. Gill CJ, Hamer DH, Simon JL, Thea DM, Sabin LL. No room for complacency about adherence to antiretroviral therapy in sub-Saharan Africa. AIDS 2005; 19:1243–1249.
6. Stolte IG, Dukers NH, Geskus RB, Coutinho RA, de Wit JB. Homosexual men change to risky sex when perceiving less threat of HIV/AIDS since availability of highly active antiretroviral therapy: a longitudinal study. AIDS 2004; 18:303–309.
7. Allen S, Lindan C, Serufilira A, Van de Perre P, Rundle AC, Nsengumuremyi F, et al
. Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women. JAMA 1991; 266:1657–1663.
8. Lindan C, Allen S, Carael M, Nsengumuremyi F, Van de Perre P, Serufilira A, et al
. Knowledge, attitudes, and perceived risk of AIDS among urban Rwandan women: relationship to HIV infection and behavior change. AIDS 1991; 5:993–1002.
9. Allen S, Serufilira A, Bogaerts J, Van de Perre P, Nsengumuremyi F, Lindan C, et al
. Confidential HIV testing and condom promotion in Africa. Impact on HIV and gonorrhea rates. JAMA 1992; 268:3338–3343.
10. Roth DL, Stewart KE, Clay OJ, van Der Straten A, Karita E, Allen S. Sexual practices of HIV discordant and concordant couples in Rwanda: effects of a testing and counselling programme for men. Int J STD AIDS 2001; 12:181–188.
11. Au J, and the Rwanda/Zambia HIV Research Group. Clinical efficacy of generic antiretroviral therapy
. In: 3rd IAS Conference on HIV Pathogenesis and Treatment
. Rio de Janiero, Brazil, 24–27 July 2005 (Abstract no. MoPe11.6C16).
12. Severe P, Leger P, Charles M, Noel F, Bonhomme G, Bois G, et al
. Antiretroviral therapy in a thousand patients with AIDS in Haiti. N Engl J Med 2005; 353:2325–2334.
13. Lifson AR, Allen S, Wolf W, Serufilira A, Kantarama G, Lindan CP, et al
. Classification of HIV infection and disease in women from Rwanda. Evaluation of the World Health Organization HIV staging system and recommended modifications. Ann Intern Med 1995; 122:262–270.
14. Calmy A, Pinoges L, Szumilin E, Zachariah R, Ford N, Ferradini L. Generic fixed-dose combination antiretroviral treatment in resource-poor settings: multicentric observational cohort. AIDS 2006; 20:1163–1169.
15. Nachega JB, Lehman DA, Hlatshwayo D, Mothopeng R, Chaisson RE, Karstaedt AS. HIV/AIDS and antiretroviral treatment knowledge, attitudes, beliefs, and practices in HIV-infected adults in Soweto, South Africa. J Acquir Immune Defic Syndr 2005; 38:196–201.
16. Bunnell R, Ekwaru JP, Solberg P, Wamai N, Bikaako-Kajura W, Were W, et al
. Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda. AIDS 2006; 20:85–92.
17. Crepaz N, Hart TA, Marks G. Highly active antiretroviral therapy and sexual risk behavior: a meta-analytic review. JAMA 2004; 292:224–236.