Pirkle C, Boileau C, Nguyen V, et al. Impact of a modified directly administered antiretroviral treatment intervention on virological outcome in HIV-infected patients treated in Burkina Faso and Mali. HIV Medicine 2009;10(3):152-6.
Many programs to provide antiretroviral therapy (ART) are operating well in sub-Saharan Africa despite the high cost of treatment. Efforts to provide ART to the vast number of persons in need of treatment have resulted in debates over how best to allocate scarce resources.(1) Of concern is the use of laboratory tests to monitor the effect of ART and the need for changes in regimens. The emergence of drug resistant HIV, most often the result of poor drug adherence, leads to poor clinical outcomes and the need to switch to more expensive medications.(2,3) Improved adherence may reduce the need for frequent laboratory tests and costs associated with changes in therapies.
To test the feasibility of using plasma viral load (VL) to identify and target persons in need of adherence assistance, which is provided as "modified directly administered ART" (mDAART)
Ouagadougou, Burkina Faso and Bamako, Mali
Pilot study of a single-arm intervention trial
ART-experienced, HIV-infected participants in a multi-centered community cohort and patients at hospital-based ART clinics whose VL was ≥500 copies/mL and who had received ART for at least six months prior to enrollment
One log10 difference in VL one month after the intervention
Participants were offered one month of mDAART with weekly follow-up visits with pharmacists or adherence counselors. mDAART was carried out by an accompagnateur, such as a family member, friend, or health care professional, all of whom were trained to monitor doses using a follow-up chart. Nonprofessionals also were provided with instruction on treatment regimen.
Trained interviewers collected sociodemographic, adherence behavior, treatment, clinical status, and self-reported health information using a questionnaire and medical records. CD4 cell counts, VL and genotype were measured before and after the intervention.
A total of 606 patients had VL measurements. Eighty-five met the study eligibility criteria and 56 participated. Non-participation was due mostly to lack of an accompagnateur. There were significant differences between participants and nonparticipants: compared with eligible, but nonparticipating cohort patients, mDAART participants had a higher body mass index (BMI; 22.85 vs. 21.01; P=50.028) and a lower VL (4.18 copies/mL vs. 4.46 copies/mL; P=50.081), and were more likely to have interrupted treatment (79.4% vs. 20.6%; P=50.038).
Genotyping was performed on 34 of the 56 patients participating in mDAART. The remaining 22 samples could not be sequenced because of sample degradation. Major nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations were M184V (85.7%), Thymidine Analog Mutation (TAM)-2 (42.9%) and TAM-1 (28.6%). Major nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations were K103N (57.1%), Y181C (32.1%) and G190A/S (22.2%).
Viral load decreased by at least 1 log10 in only one third of mDAART participants. Of the 34 genotyped participants, 30 had major resistance mutations. In the majority (90%) of participants with drug resistance, VL did not decrease after mDAART. Among genotyped participants, 78.6% had both NRTI and NNRTI mutations and 76.7% had three or more mutations. Of the three resistant participants who reduced their VL by ≥1 log10, none had dual NRTI/NNRTI mutations and all had fewer than three mutations.
Although VL was useful in identifying patients in need of adherence assistance, mDAART was associated with a VL decrease of at least 1 log10 in only one third of participants. The presence of resistance suggests that poor adherence may have been occurring well before the trial.
Use of Cochrane-based quality ratings for this study is not appropriate because it was a pilot study. As a feasibility study, it was successful in demonstrating the difficulties that would be likely to occur if this had been a large-scale intervention trial and clearly demonstrates the value of pilot studies.
Because this was a pilot study it is difficult to address programs with these data. However, the results do suggest that patients are either infected with drug-resistant HIV or are developing resistance shortly after initiation of treatment. Thus, it may be that adherence was never optimal and if this is true, efforts to improve adherence are urgently needed. The difficulty in finding accompagnateurs suggests that alternative methods of improving adherence should be considered. The use of DAART may be effective but its effective delivery is likely to require more than the use of an accompagnateur.
- Calmy A, Ford N, Hirschel B, et al. HIV viral load monitoring in resource-limited regions: optional or necessary? Clin Infect Dis 2007;44:128-34.
- Koenig SP, Kuritzkes DR, Hirsch MS, et al. Monitoring HIV treatment in developing countries. BMJ 2006;332:602-4.
- Kagay CR, Porco TC, Liechty CA, et al. Modeling the impact of modified directly observed antiretroviral therapy on HIV suppression and resistance, disease progression, and death. Clin Infect Dis 2004;38 (Suppl. 5):S414-20.