Treatment-for-prevention:  clinical considerations.
OBJECTIVE
This article will discuss some of the potential clinical implications of the widespread use of antiretroviral treatment-as-prevention in patients with high CD4 cell counts, including the balance of clinical benefit vs. toxicity, adherence, drug resistance, and risk compensation.


RESULTS
Recent studies have definitively demonstrated that antiretroviral treatment (ART) markedly reduces heterosexual transmission of HIV-1 to HIV-uninfected partners among patients with CD4 counts less than 550 cells/μl. At the same time, an increasing body of evidence suggests that uncontrolled HIV replication may be associated with immune activation and inflammation, both of which increase the risk of non-HIV-related diseases; and that initiation of ART at even higher CD4 counts might improve patient outcomes. ART regimens continue to become better-tolerated, safer, and easier to take, and rates of adherence and virologic suppression also appear to be improving. Nevertheless, acceptability of and adherence to 'treatment for prevention' are unknown, and the spread of drug resistance in the setting of suboptimal adherence among less-motivated patients are substantive concerns with treatment-for-prevention.


CONCLUSIONS
Earlier ART may confer clinical benefits, and ART regimens are becoming safer and better-tolerated. However, high-quality data are urgently needed with regards to the acceptability of, adherence to, and clinical outcomes with treatment-for-prevention among patients with high CD4 counts, as well as risk compensation and the emergence and spread of drug resistance that may occur with implementation of this HIV prevention strategy.
Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA. slockman@hsph.harvard.edu
Shahin
S
Lockman
Paul
P
Sax
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D006679:HIV Seropositivity / Q000175:diagnosis / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D055118:Medication Adherence; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D019380:Anti-HIV Agents