Genetics and biology of drug-resistant HIV

Of the 35 million people infected with HIV worldwide, 15 million are now receiving antiretroviral therapy - and this number is set to rise steeply following recommendations for universal treatment. Drug resistance arises commonly in resource-limited settings but goes largely undetected. Resistance to a core drug class, protease inhibitors, is poorly understood but probably involves multiple HIV genes. To date, scientific analyses have been limited to just one gene, protease, often using simple cell-line-based assays. It is now possible to sequence and generate whole viruses derived from patients in models of infection that more closely resemble in vivo conditions. This will allow detection of changes in virus resistance patterns with greater accuracy than ever before, with phenotypic evaluation of their impact in relevant models. This information will inform field tests designed to detect protease-inhibitor-resistant strains and help to plan strategy for further lines of antiretroviral therapy.