Table 2.
Reported Associations with Pharmacy-Based Adherence Measures (PAMs) in Low- and Middle-Income Countries
| Study (year) | Design | Type of care | Region | ART naive | ART regimen (%)a | PAM category | PAM definition in study | PAM monthsb | Sample size, no. of persons | Key findingsc |
| Nachega et al [13] (2006) | Retrospective cohort | Private | Sub-Saharan Africa (multiple countries) | Yes | NNRTI (82), PI | MPR | Months ART claims submitted (entire regimen)/months from start to death, withdrawal or censor | Variable; median, 22 |
6288 | 1. PAM <80% predicted death and death + LTFU (P < .01) 2. compared with PAM adherence of 100%, decreasing PAM strata increasingly predicted death (P < .01), except for PAM adherence of 80%–99% |
| MPR | Months ART claims submitted (entire regimen)/Months in the interval | 12 (0–12) | 3267 | PAM <80% in first 12 months predicted death (P < .01) | ||||||
| Weidle et al [26] (2006) | Clinical trial | Home based | Uganda | Yes | NNRTI (100) | PCf | (Days 3TC delivered - days 3TC returned)/days in the interval | 3 (3–6) 3 (9–12) |
913 894 |
1. PAM <95% predicted VFd at 6 or 12 months (P < .01) 2. self-report predicted VF at 12 (P < .05) but not 6 months |
| PC | (3TC Pills delivered – 3TC pills returned)/3C pills delivered | 3 (3–6) 3 (9–12) |
913 894 |
PAM <95% predicted VFd at 6 or 12 months (P < .05) | ||||||
| Nachega et al [4] (2007) | Retrospective cohort | Private | Sub-Saharan Africa (multiple countries) | Yes | NNRTI (100) | MPR | Months ART claims submitted (all ARVs)/months from start to death/leaving/censor | Variable median, 26 |
2821 | PAM strata >50% increasingly predicted sustained VL suppression (P < .01), shorter time to VL suppression (P < .05), and increased time to viral rebound e (P < .05) |
| Bisson et al [17] (2008) | Retrospective cohort | Private | Sub-Saharan Africa (multiple countries) | Yes | NNRTI (100) | MPR | Months ART claims submitted (all ARVs)/months from start to study endpoint | 6 (0–6) 12 (0–12) |
958 872 |
1. PAM <90% predicted VFc at 6 and 12 months (P < .01) 2.it was better than changes in the CD4 cell count at predicting VFd at 6 and 12 months (P < .01) |
| Variable median, 20 |
1101 | 1. PAM <90% predicted viral rebounde (P < .05) 2.not different than changes in the CD4 cell count from maximum on-treatment value in predicting viral rebounde |
||||||||
| 3 (0–3) 3 (6–9) |
958 872 |
PAM was no better than changes in the CD4 cell count over first 6 or 12 months in predicting VFc at 6 or 12 months | ||||||||
| Bisson et al [18] (2008) | Case-control | Public | Botswana | No | NNRTI (100) | PC | Sum of (days ART prescribed – remnant days ART) between last and 3 prior fills/days between last and 3 prior fills | 3 (varied) | 302 | 1. Decreasing PAM rates (90%-95%, 80%-90%, and <80% 2. (P < .05) and PAM <95% (P < .01) in 3 months prior to recruitment predicted VF,d compared with PAM >95% |
| Goldman et al [23] (2008) | Retrospective cohort (all clinical or IF) | Public | Zambia | Yes | NNRTI (100) | MPR | 100% - [(days late to pharmacy visits – 3)/days on ART] g | Variable Median, 24 |
913 | 1. Lower PAM (<80%, 80%-94%, and >95%) more likely to predict VFd at time of the VL test (P < .05) 2. Self-reported adherence did not predict VFd |
| San Lio et al [25] (2008) | Prospective cohort | NGO, free | Mozambique | No | NNRTI (100) | PC | (Days pills prescribed – days pills returned)/days between appointments | 12 (varied) | 394 | PAM <95% predicted VFh after 12 months of follow-up (P < .05) |
| Toure et al [20] (2008) | Retrospective cohort | Public, private and NGO | Cote d'Ivoire | Yes | NNRTI (96), PI, 3NRTI | MPR | Days ART given to patient/days since ART start to last visit, or censor if last visit was after censor date | Variable median, 8 |
10211 | 1. PAM <80% predicted increases in the CD4 cell count of <50 cells after 6 months (P < .01) 2. PAM <80% predicted LTFU (P < .01) but not death over a period of 16 months |
| Chi et al [19] (2009) | Retrospective cohort | Public | Zambia | Yes | NNRTI (100) | MPR | 100% - [(days late to pharmacy visits – 3)g/days on ART] | 12 (0–12) | 27115 | 1. PAM <80% predicted lower CD4 cell counts after 18–36 months (P < .01) 2. decreasing PAM adherence rates (>95%, 80%-94%, and <80%) predicted LTFU after 12-36 months of ARTh (P < .01) PAM <80% predicted death (P < .01) at 12–36 months but higher strata (80%-94% and >95%) did not |
| Danel et al [22] (2009) | Clinical trial (one or both of VF or IF) | Free | Cote d'Ivoire | Yes | NNRTI (87), PI | MPR | Days ART delivered/days in the interval | 6 (0–6) | 208 | PAM of >90% did not predict CD4 cell counts of >350 cells/μL plus VL suppression at 36 months |
| 30 (6–36) | 208 | PAM >90% predicted either or both of the following: a CD4 cell count >350 cells/μL and VL suppression at 36 months (P < .01) | ||||||||
| Rougemont et al [24] (2009) | Prospective cohort | Private | Cameroon | Yes | NNRTI (99), PI | PPU | “Nonadherent was defined as being >2 weeks late to pick-up medication or as “abandoned ART” on phone tracing | 6 (0–6) | 194 | ”Nonadherent” status predicted VFd (P < .01); no different than CD4 cell count change over 6 months at predicting VFd; day 30 Self-reported adherence did not predict 6-month VFd |
| Ross-Degnan et al [21] (2010) | Retrospective cohort | Public, private, and NGO | Sub-Saharan Africa (multiple countries) | Yes | NNRTI, PI (NR) | MPR | Days with ART/days since ART start | Variable median, 6 |
409 | 1. PAM <80% (but not 80%-90% or 90%-100%) predicted lower CD4 cell counts (at 4-9 months), compared with PAM 100% (P < .05) 2. PAMs were not directly compared with self-reported adherence |
| MPR | ”Nonadherent” was defined as >30 days without receipt of ART | Variable Median, 6 |
409 | “Nonadherent” status predicted lower CD4 cell counts at 4-9 months (P < .05) |
NOTE. ART, antiretroviral therapy; ARV, antiretroviral; IF, immunological failure; LTFU, lost to follow-up; MPR, medication possession ratio; NGO, nongovernmental organization; NNRTI, nonnucleoside reverse-transcriptase inhibitor; NR, not reported; PC, pill count; PI, protease inhibitor; 3NRTI, triple nucleoside reverse-transcriptase inhibitor; 3TC, lamivudine; VF, virological failure; PPU, pill pick-up; VL, viral load.
Data are ART regimens for that study. Number in parentheses represents percentage of subjects receiving the predominant regimen.
Duration of adherence assessment, with the months over which assessed in parentheses. If there was a variable duration of adherence assessment, than the median, mean, or range is listed.
Number after PAM is the percentage adherence.
Single viral load above threshold.
Single viral load above threshold after previous VL suppression.
Because remnant pills were counted to determine adherence, this measure comes under the PC category despite being referred to as medication possession ratio in the study.
Subjects not late to pharmacy visit until after 3 days, to account for routine provision of 3 days extra ART.
Statistical significance for association was not reported, so we determined statistical significance using raw data with the χ2 test.