Nelfinavir (Viracept) is able to reduce viral load and increase CD4 cell counts in many people when combined with at least two other antiretroviral drugs. In the past, it was one of the most frequently prescribed drugs for first-line therapy, because its resistance profile offers opportunities for second-line protease inhibitor therapy^[1].

Nelfinavir was approved after studies found that it produced better outcomes when combined with nucleoside reverse transcriptase inhibitors (NRTIs) than NRTIs alone. In the first study, adding nelfinavir to d4T (stavudine, Zerit) brought about greater reductions in viral load and increases in CD4 cell counts than d4T alone. A second study examining the addition of nelfinavir to AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir) reached similar conclusions^[2].

More recently, nelfinavir’s potency relative to other protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been drawn into question. Consequently, currently favoured first-line regimens usually include an NNRTI, such as efavirenz (Sustiva), or a ritonavir (Norvir)-boosted protease inhibitor, such as ritonavir-boosted lopinavir (Kaletra).

For example, 60-week results of a head-to-head study of nelfinavir and Kaletra found that Kaletra-based treatment was significantly more potent^[3]. Similarly, the Combine study found that the NNRTI nevirapine (Viramune) produces a better virological outcome than nelfinavir, especially in individuals with baseline viral loads above 100,000 copies/ml^[4]. However, Roche, nelfinavir’s manufacturers, have argued that the drug’s poor performance in this study is largely attributable to the reluctance of participants to take their medications three times a day, leading to a higher drop-out rate among those on nelfinavir.

Subsequently, studies have found that fosamprenavir (Telzir) is more potent than nelfinavir in people with baseline viral loads above 100,000 copies/ml. Furthermore, it has been reported that viral rebound is more common in patients taking nelfinavir than those taking efavirenz^[5][6][7].

Nelfinavir-based regimens have shown efficacy in patients with substantial treatment experience, making it an option for the construction of salvage treatment regimens^[8][9].

Genetic polymorphisms in the genes for two liver enzymes have been linked to blood levels of nelfinavir, with one of these being associated with an increased risk of treatment failure^[10]. For more information, see Genetics and HIV treatment.