Partial treatment interruptions

Many patients with drug-resistant HIV and limited therapeutic options for complete suppression are maintained on a stable partially suppressive regimen. Although this approach is associated with durable clinical benefit (compared with no therapy), it can result in the accumulation of drug-resistance mutations and the development of drug-related toxicities. Several strategies aimed at maintaining the partial activity of therapy while reducing drug exposure have recently been investigated. Findings from these studies have provided important insights into how drugs work in the presence of drug-resistant viremia.

Nucleoside analogues often continue to exert potent antiviral activity against viruses exhibiting evidence of genotypic and phenotypic drug resistance. Protease inhibitors and fusion inhibitors select for mutations that often confer complete resistance in vivo; these mutations, however, reduce viral fitness (as measured in the absence of drug) and may reduce virulence/pathogenicity. Nonnucleoside reverse transcriptase inhibitors generally lack any beneficial activity once drug-resistant mutations have emerged.

Although these approaches are not recommended for routine clinical practice, they have provided the requisite proof-of-concept to motivate larger controlled randomized trials. More importantly, findings from these studies have generated a number of important insights that can be valuable when considering 'when to switch', 'how to switch' and 'how to wait'.