HIV-1 genotypic resistance in structured treatment interruptions

Highly active anti-retroviral therapy (HAART) represents perhaps the most significant therapeutic advance in HIV research to date, and is the basis of a significant decline in morbidity and mortality rates among patients. However, current antirretroviral regimens are limited by issues of potency, adherence, toxicity, resistance and cost. Hence, eradication of the virus has not been achieved and so treatment has to be maintained for the remainder of the patients' lives. Structured treatment interruptions (STI) offer an alternative to continuous HAART. STI involves alternating on-and-off cycles of HAART in order to enhance the utility of therapy. One of the main risks is selection of resistance mutations. In this review, we will examine if the presence of any drug-resistance mutations detected during STI are selected de novo or if they are from archived mutations. Moreover, we will review the relationship between the presence of drug resistance mutations and the achievement undetectable viral load after treatment reintroduction. Finally, we will study whether the appearance of drug resistance mutations during STI is favoured by specific antiretroviral drugs.