Box 1 | Evolution of highly active antiretroviral therapy for HIV

The highly active antiretroviral therapy (HAART) for HIV (human immunodeficiency virus) infection, based on a combination of different antiviral drugs, started in 1996. Over the past decade, HAART has gradually evolved from drug regimens with more than 20 pills daily (including stavudine plus lamivudine plus indinavir) in 1996, to 3 pills daily (that is, zidovudine/lamivudine (Combivir) twice daily and efavirenz (EFV) once daily) in 2003, to 2 pills daily (that is, emtricitabine ((–)FTC)/tenofovir disoproxil fumarate (Truvada) and EFV) in 2004, and finally one pill daily in 2006 (Atripla, which contains tenofovir disoproxil fumarate (TDF) (300 mg) plus emtricitabine (200 mg) and EFV (600 mg))¹⁵³. Atripla is the first anti-HIV pill (to be taken once daily) that contains three active ingredients belonging to three different classes of HIV inhibitors (nucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors).

The triple-drug combination TDF, (–)FTC and EFV has been the subject of a randomized (1:1), open-label, non-inferiority trial in antiretroviral-naive patients (study GS 934) comparing the efficacy of TDF, (–)FTC and EFV versus Combivir (zidovudine/lamivudine) and EFV¹⁵⁴. After 96 weeks of treatment, 75% of the patients in the TDF/(–)FTC/EFV arm compared with 62% of the patients in the Combivir/EFV arm achieved a viral load of less than 400 copies per mL¹⁵⁵. Patients receiving TDF/(–)FTC/EFV also experienced a greater increase from baseline in CD4⁺ cell counts compared with those receiving Combivir/EFV (270 versus 237 per l, p = 0.036)¹⁵⁵. Moreover, after 96 weeks of treatment, discontinuation of the antiretroviral medications due to adverse events was higher among Combivir/EFV patients compared with the TDF/(–)FTC/EFV arm (11% versus 5%, p = 0.08), the most common cause of discontinuation being anaemia (6% in the Combivir/EFV arm versus 0% in the TDF/(–)FTC/EFV arm)¹⁵⁵. Also, patients receiving TDF/(–)FTC/EFV had a significantly greater median increase in body weight and limb fat compared with patients receiving Combivir/EFV; and no patient discontinued study medication due to renal events in either arm. It could be concluded that over the 96-week study period, the combination of TDF, (–)FTC and EFV was superior to Combivir and EFV, with regard to both efficacy (virologic and immunologic response) and safety (side effects)¹⁵⁵.