Nachega JB, Hislop M, Nguyen H, et al. Antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in southern Africa. J Acquir Immune Defic Syndr 2009 May 1;51(1):65-71.
Several large trials have evaluated the efficacy of antiretroviral therapy (ART) in adults and pediatric populations;(1,2,3) however, there are scant data on ART adherence and virologic outcomes in adolescents, especially those in low- and middle-income countries. Adolescents may be less adherent to ART than are adults, and thus their health outcomes may be less favorable; therefore, study authors note, it is important to measure adherence and virologic outcomes in this population.
To determine adherence to and effectiveness of ART in adolescents compared with adults in southern Africa
Observational cohort study
Aid for AIDS, a private sector, employer-subsidized disease management program that operates in nine countries in southern Africa
Patients who initiated ART between January 1999 and August 2006 who met the following inclusion criteria: 1) no known prior exposure to ART; 2) age ≥11 years at ART initiation; 3) at least 6 months of follow-up data available; 4) a baseline (pre-ART) HIV viral load of >400 copies/mL; and 5) at least one known viral load measurement within 1 year of ART initiation.
Participants were divided into three age groups, adolescents (aged 11-19 years), young adults (aged 20-29 years), and adults (aged ≥30 years). A total of 7776 eligible participants were included in the study: 154 adolescents, 1380 young adults, and 6242 adults. For the purposes of some analyses, young adults and adults were collapsed into one group, with a total sample adult population of 7622.
The primary outcomes were virologic suppression (HIV viral load of ≤400 copies/mL) and viral rebound, defined as virologic failure (viral load of >400 copies/mL) after achieving virologic suppression.
Records from eligible HIV-infected adults and adolescents enrolled in Aid for AIDS were evaluated. Aid for AIDS does not have its own clinics, but instead reimburses patients' private medical practitioners. Patients were considered eligible for ART if they had at least two documented CD4 T-cell counts of <350 cells/µL or a medical confirmation of an AIDS-defining illness. Being on ART was defined as taking a minimum of two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI). Each patient chose the pharmacy at which their ART was dispensed monthly.
Adherence was estimated by pharmacy refills, calculated as the total number of months in which ART medications were claimed divided by the total number of months during which ART was prescribed.
Follow-up continued from initiation of ART until 1) a change in ART regimen; 2) loss to follow-up; 3) death; or 4) reaching the study end in February 2007. Patients who left their medical insurance fund, or whose medical insurance fund changed to a different disease management program, were censored as "lost to follow-up" at the date of departure.
Adolescents on ART were more likely than adults to be female (72.7% vs. 62.3%; P=0.01) and to initiate ART in 2003 or later (50.1% vs. 40.3%; P=0.02). Adolescents were less likely to get NNRTI-based ART (92% vs. 97.2%; P<0.001) and more likely to have a shorter follow-up duration. Median follow-up in adolescents was 27 months (interquartile range [IQR] 18.1-43.7) and in adults was 36.9 months (IQR 23.6-54.5; P<0.001).
Adolescents had significantly lower adherence rates than did adults. At 6 months, 20.7% of adolescents achieved 100% adherence; at 12 months, 14.3%; and at 24 months, 6.6%. For adults, corresponding figures were 40.5% at 6 months, 27.9% at 12 months, and 20.6% at 24 months (P<0.01 at all time points). The proportion of adolescents achieving viral suppression (HIV viral load of ≤400 copies/mL) during the study was lower than that of adults. At 6 months after initiation of ART, 63.0% of adolescents achieved viral suppression; at 12 months, 45.7%; at 18 months, 45.3%; and at 24 months, 43.6%. For adults, corresponding figures were 69.3% at 6 months, 62.1% at 12 months, 60.2% at 18 months, and 62.3% at 24 months (P<0.05 at 12, 18, and 24 months).
In the subset of patients who achieved initial virologic suppression (5504 adults and 93 adolescents), 3805 adults and 62 adolescents had at least one viral load measurement of >400 copies/mL after initial suppression. Following 6 months of treatment, 31.1% of adolescents achieved viral rebound, at 12 months 42.4%, at 18 months 38.9%, and at 24 months 37.5%. For adults, corresponding figures were 16.6% at 6 months, 20.2% at 12 months, 21.5% at 18 months, and 24.2% at 24 months (P<0.05 at 6 and 12 months). In Cox proportional hazards models adjusted for baseline characteristics and adherence, adolescents who achieved initial virologic suppression had significantly shorter times to viral rebound than did adults (HR 2.18; 95% confidence interval [CI]:1.41-3.38; P<0.001).
Results from this study suggest that HIV-infected adolescents and young adults in southern Africa who are on ART have both poorer adherence rates and poorer virologic outcomes than do adults. Compared with adults, adolescents had lower rates of virologic suppression at all time points after ART initiation and experienced more rapid viral rebound.
Using the Newcastle-Ottawa quality assessment scale for cohort studies, this study received 7 of 9 points. One point was deducted because of the very small sample size of adolescents in the study (154 adolescents vs. 7622 adults). One point was deducted because authors did not discuss rates of loss to follow-up. Of note, medication adherence was measured indirectly by pharmacy refills, calculated as the total number of months in which ART medications were claimed divided by the total number of months during which ART was authorized. Nonetheless, using pharmacy refills as a measure of adherence has been validated.(4,5)
Adherence rates observed in adolescent patients in the study underscore the urgent need to identify risk factors that contribute to poor adherence in HIV-infected adolescents in sub-Saharan Africa. Given the poorer health outcomes associated with lower rates of adherence among the adolescents in this study, further research is needed to determine barriers to adherence in adolescents and to develop targeted interventions to improve adherence rates in this population.
- Murphy DA, Belzer M, Durako SJ, et al, and Adolescent Medicine HIV/AIDS Research Network. Longitudinal antiretroviral adherence among adolescents infected with human immunodeficiency virus. Arch Pediatr Adolesc Med 2005;159:764-70.
- Murphy DA, Sarr M, Durako SJ, et al, for the Adolescent Medicine HIV/AIDS Research Network. Barriers to HAART adherence among human immunodeficiency virus-infected adolescents. Arch Pediatr Adolesc Med 2003;157:249-55.
- Flynn PM, Rudy BJ, Lindsey JC, et al, and PACTG 381 Study Team. Long-term observation of adolescents initiating HAART therapy: three-year follow-up. AIDS Res Hum Retroviruses 2007;23:1208-14.
- Gross R, Yip B, Lo Re V III, et al. A simple, dynamic measure of antiretroviral therapy adherence predicts failure to maintain HIV-1 suppression. J Infect Dis 2006;194:1108-14.
- Grossberg R, Zhang YW, Gross R. A time-to-prescription-refill measure of antiretroviral adherence predicted changes in viral load in HIV. J Clin Epidemiol 2004;57:1107-10.