Efavirenz (Sustiva) is a powerful anti-HIV drug, which must be taken in combination with other antiretroviral drugs. It has been proven to reduce HIV-1 viral load to below 400 copies/ml within six months in 60 to 80% of people who have not previously taken any anti-HIV treatments. Efavirenz is not active against HIV-2.

Efavirenz’s potency was demonstrated in study 006, in which efavirenz was found to be superior to indinavir (Crixivan), when either drug was combined with AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir). After three years, more patients taking efavirenz maintained viral suppression, even in patients with viral loads above 300,000 copies/ml before treatment began^[1]. Researchers have estimated that the average time to virological failure on efavirenz, AZT and 3TC is six years, based on long-term follow-up of this study^[2].

Efavirenz-based treatment is also effective in patients starting therapy with CD4 cell counts below 100 cells/mm^3[3]. However, its efficacy has not been assessed in patients starting with CD4 cell counts below 50 cells/mm³ or after failure of protease inhibitor-containing regimens.

A large scale, comparative study called ACTG 384, was completed in 2002. It found that efavirenz, AZT and 3TC was the preferred first-line therapy in terms of antiviral efficacy and toxicity after 144 weeks of follow-up^[4][5]. In addition, two observational studies have suggested that people taking efavirenz are more likely to achieve and sustain undetectable viral load than those taking a protease inhibitor^[6][7]. Similarly, a retrospective study based in San Francisco has shown that first-line anti-HIV drug regimens containing efavirenz give better survival outcomes than any other combinations available prior to 2002^[8]. Another randomised study, which compared efavirenz with d4T (stavudine, Zerit) and ritonavir (Norvir)-boosted amprenavir (Agenerase) when taken in combination with AZT and 3TC, has also favoured efavirenz as first-line treatment^[9]. Similarly, efavirenz is more likely to suppress viral load than the protease inhibitor nelfinavir (Viracept) when combined with d4T and ddI (didanosine, Videx), although the two drugs have similar immunological outcomes^[10].

There is some dispute about the comparative efficacy of the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine (Viramune). The randomised 2NN study showed that nevirapine was not inferior to efavirenz, although the participants taking efavirenz experienced fewer side-effects^[11]. Quality of life was also similar in patients taking nevirapine and efavirenz^[12]. Despite this, based on several large cohort studies that have found efavirenz to be superior to nevirapine in terms of efficacy and rebound rates, United States treatment guidelines recommend efavirenz as the preferred NNRTI in first-line treatment^{[13][14][15][16]}. British guidelines do not endorse efavirenz as the superior NNRTI, and suggest that drug choices should be individualised.

There are encouraging data on the effectiveness of efavirenz among people who have previously taken NRTIs and protease inhibitors. Generally, second-line and salvage combinations including efavirenz work more effectively when new NRTIs are added. Several studies have shown that efavirenz plus protease inhibitors and NRTIs can suppress HIV to undetectable levels for about half of people who have failed previous NRTI and protease inhibitor combinations. For example, a small study of efavirenz, saquinavir (Invirase) and ritonavir plus NRTIs was tested on protease inhibitor-experienced individuals. Seventy per cent achieved viral loads below 500 copies/ml after six months of treatment, and 45% had viral loads below 50 copies/ml^[17].

There is a growing body of research indicating that switching to efavirenz from a protease inhibitor is an effective strategy. For example, one large, randomised study found that the likelihood of adhering to the drug regimen and maintaining viral suppression after one year was greater among people who substituted efavirenz for a protease inhibitor than those who continued on protease inhibitor therapy^[18]. Results from the Swiss HIV Cohort also indicate that people who switch from a protease inhibitor to efavirenz are more likely to maintain virological control one year after switching, although a recent study has suggested that this may be due to better adherence associated with an regimen that is easier to take^[19][20].

There is evidence to suggest that efavirenz penetrates the cerebrospinal fluid that surrounds the brain and the spinal cord, and that it may be effective against HIV in the brain. One small study found that efavirenz-containing drug combinations reduced the amount of HIV in the cerebrospinal fluid to below 400 copies/ml in nine people over 26 weeks^[21]. There is also evidence that a combination containing efavirenz can reduce HIV in the lymph tissue to very low levels^[22].

HIV-positive African Americans taking efavirenz are less likely to experience immunological failure than Caucasians, which may be due to a high prevalence of a genetic variant that slows down clearance of the drug^[23][24]. This variant also means that patients stopping efavirenz treatment who have this variant are at risk of developing efavirenz resistance for an extended period, while drug levels fall^[25].