HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia, and insulin resistance. The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the retinoid X receptor; and peroxisome proliferator activated receptor type gamma (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would impair hepatic chylomicron uptake and triglyceride clearance by the endothelial LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to central fat deposition (and in the breasts in the presence of oestrogen), insulin resistance, and, in susceptible individuals, type 2 diabetes. Understanding the syndrome's pathogenesis should lead to treatment strategies and to the design of protease inhibitors that do not cause this syndrome.

Genetics, cell biology, and whole-genome sequencing of pathogens have changed dramatically the opportunities to investigate the epidemiology, pathogenesis, diagnosis, and control of microbial diseases. For example, recombinant DNA and PCR are powerful tools used to isolate genes whose role in pathogenicity can be investigated in biologically relevant virulence assays. Vaccines that target one or more of these genes can then be developed. Complete genome sequences of microbes provide an inventory of the genes encoding every virulence factor and potential immunogen. Candidate vaccines can be selected and developed using various approaches, including the recent innovation of immunisation with nucleic acids. Although many successful vaccines have been and will continue to be developed through empirical approaches, molecular microbiology provides a rational basis for discovery, development, and implementation of safer, more effective and, potentially cheaper vaccines.