Effectiveness

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 a 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).

K aletra 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 fosamprenavir (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 may be superior in terms of the magnitude of viral suppression.⁹

In ACTG 5142, patients received one of three regimens: efavirenz+ 2 NRTIs, Kaletra (LPV/r) + 2 NRTIs, or an NRTI-sparing combination of efavirenz and Kaletra. The NRTI options were 3TC or FTC combined with stavudine (d4T), TDF, or zidovudine (ZDV). At the start of the study, the median viral load was approximately 100,000 copies/ml and the median CD4 cell count was 182 cells/mm³, suggesting that the study population had relatively advanced HIV disease and was starting treatment later than current guidelines recommended.

By intent-to-treat analysis, 89% of the participants receiving efavirenz-based triple therapy had viral loads below 50 copies/ml after 96 weeks, as compared with 77% receiving Kaletra-based triple therapy.¹⁰

The researchers were unclear why fewer participants on Kaletra-based triple therapy achieved viral loads below 50 copies/ml at week 96, compared with those on efavirenz-based triple therapy, since they found that the time to treatment-limiting toxicity was similar for all arms, and the proportion of grade 3 or 4 clinical adverse events was similar in each arm, at around 20%.

There is 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.¹¹ Similar effects were observed when Kaletra was combined with efavirenz (Sustiva), with 65% of patients having undetectable viral loads after 48 weeks.¹²

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.^{13 14 15 16}

Because of its long half-life and high genetic barrier to resistance, Kaletra has been investigated as an option for monotherapy in treatment-naive and -experienced patients. At least three 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.^{17 18 19 20 21} However, these trials have generally found inferior levels of viral suppression to trials of combination therapy including Kaletra. ²²

MONARK, a prospective, open-label, randomized, 96-week trial comparing the safety and efficacy of lopinavir/ritonavir monotherapy with a standard lopinavir/ritonavir plus zidovudine and lamivudine regimen as an initial treatment regimen in treatment-naive HIV-infected patients with HIV-RNA levels less than 100,000 copies/ml. At the week 48 on-treatment analysis, 80% in the monotherapy group and 95% of those on triple therapy achieved a viral load less than 400 copies/ml (intent to treat analysis was 64 v 75% respectively). This indicates that monotherapy should not be considered as a preferred treatment option for use in antiretroviral-naive patients.²³

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}