Kaletra is a powerful anti-HIV drug. Studies suggest that approximately 75 to 90% of people who start treatment with Kaletra plus nucleoside reverse transcriptase inhibitors (NRTIs) achieve a viral load below 400 copies/ml after one year, and 70% maintain viral loads below 50 copies/ml after four years^[1][2][3][4]. Some patients in the original study of Kaletra in treatment-naive patients have been taking the drug for over six years, with persistently undetectable viral loads^[5]. The strength of current evidence in favour of Kaletra has led experts in the United Kingdom and the United States to recommend Kaletra as the preferred first-line protease inhibitor.

Kaletra-based regimens appear to be more potent than single protease inhibitor-based regimens in people who have not previously taken HIV treatment. For example, head-to-head studies have shown that Kaletra is more potent than nelfinavir (Viracept) and atazanavir (Reyataz). Kaletra has also been compared to other ritonavir (Norvir)-boosted protease inhibitors. For example, the MaxCmin2 study found that Kaletra is superior to ritonavir-boosted saquinavir (Invirase), with fewer people taking Kaletra dropping out due to side-effects^[6]. In contrast, the KLEAN study found that Kaletra is of similar effectiveness to ritonavir-boosted fosamprenavi (Telzir)^[7].

Studies conducted in people who have previously taken protease inhibitors also suggest that Kaletra has similar efficacy to other ritonavir-boosted protease inhibitors. One study found that Kaletra and ritonavir-boosted atazanavir had similar outcomes in terms of viral loads and CD4 cell counts, despite less favourable effects on blood lipids with Kaletra^[8]. A comparative study of Kaletra and ritonavir-boosted fosamprenavir showed equivalence in terms of the proportion of people achieving undetectable viral loads, although Kaletra maybe superior in terms of the magnitude of viral suppression^[9].

There is also encouraging evidence that Kaletra is an effective component of salvage therapy. For example, Kaletra and nevirapine (Viramune) plus NRTIs suppressed viral load below 400 copies/ml in 70% patients after 48 weeks^[10]. Similar effects were observed when Kaletra was combined with efavirenz (Sustiva), with 65% of patients having undetectable viral loads after 48 weeks^[11].

For people who cannot take NRTIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs) due to resistance or toxicities, combinations including Kaletra and other protease inhibitors. Preliminary results suggest this may be a reasonably effective salvage strategy. Studies have examined the effects of combining Kaletra with the protease inhibitors saquinavir, indinavir (Crixivan) and atazanavir, with results indicating that these combinations are safe and effective^{[12][13][14][15]}. A combination of lopinavir, amprenavir and ritonavir at the higher dose of either 200 or 400mg per day is also an effective salvage regimen in highly treatment-experienced patients^[16].

Because of its long half-life and high genetic barrier to resistance, Kaletra has recently been investigated as an option for monotherapy in treatment-naive and -experienced patients, with encouraging results. The MONARK study has found that patients starting treatment with Kaletra monotherapy are as likely as those starting with Kaletra plus two NRTIs to fail treatment after 48 weeks, defined as viral load rising to above 400 copies/ml. The two options also bring about similar CD4 cell count rises^[17].

Similarly, at least three other studies have demonstrated that switching from Kaletra or efavirenz (Sustiva) plus two NRTIs to Kaletra monotherapy leads to comparable virologic outcomes to patients randomised to remain on triple therapy after up to 48 weeks, with similar rates of resistance and blood fat elevations^{[18][19][20] [21][22]}. However, these trials have generally found inferior levels of viral suppression to trials of combination therapy including Kaletra, and are often too small to be able to detect a meaningful difference between Kaletra alone and combination therapy^[23]. Until the results of larger trials are available, monotherapy cannot be recommended.

Recent studies have shown that levels of lopinavir in the cerebrospinal fluid are low, but they are sufficient to inhibit HIV replication in patients who are adherent to Kaletra^[24][25][26].