Modeling the impact of modified directly observed antiretroviral therapy on HIV suppression and resistance, disease progression, and death.
A simulation model that used Markov assumptions with Monte Carlo uncertainty analysis was evaluated 1500 times at 10,000 iterations. Modified directly observed therapy (MDOT) for human immunodeficiency virus was assumed to improve adherence to therapy to 90% of prescribed doses. The impact of MDOT interventions on modeled biological and clinical outcomes was compared for populations with mean rates of adherence (i.e., the mean percentage of prescribed doses taken by each member of the population who had not discontinued therapy) of 40%, 50%, 60%, and 70%. MDOT reduced the risk of virological failure, development of opportunistic infections, and death, yet increased the risk of drug resistance, for each adherence distribution among persons with detectable plasma virus loads. Over 1500 trials, for a population with 50% adherence to therapy and a 12-month period, MDOT increased the median rate of virological suppression from 13.2% to 37.0% of patients, decreased the rate of opportunistic infection from 5.7% to 4.3% of patients, and decreased the death rate from 2.9% to 2.2% of patients. In the same population, however, MDOT increased the rate of new drug resistance mutations from 1.00 to 1.41 per person during the 12-month period. The impact of MDOT was smaller in populations with higher levels of adherence. MDOT interventions will likely improve clinical outcomes in populations with low levels of adherence but may not be effective at preventing drug resistance in treatment-experienced populations. MDOT may be more effective in preventing drug resistance with potent regimens in treatment-naive patients.
Kagay
C R
CR
University of California, San Francisco, School of Medicine, San Francisco, California 94110, USA.
Porco
T C
TC
Liechty
C A
CA
Charlebois
E
E
Clark
R
R
Guzman
D
D
Moss
A R
AR
Bangsberg
D R
DR
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D003643:Death; D023801:Directly Observed Therapy; D018450:Disease Progression; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000150:complications / Q000401:mortality* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015233:Models, Statistical; D010349:Patient Compliance
D019380:Anti-HIV Agents