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Lopinavir Monotherapy Fails More in People With Non-B Subtypes
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11th European AIDS Conference
October 24-27, 2007
Madrid
Mark Mascolini
Closer analysis of a trial comparing lopinavir/ritonavir monotherapy with lopinavir/ritonavir plus AZT/3TC in antiretroviral-naive people disclosed that infection with an HIV-1 subtype other than B independently inflated the risk of monotherapy failure [1]. But a few findings suggested socioeconomic factors related to non-B infection--rather than a non-B-specific virologic factor--explain the higher failure risk. Pinning down the explanation could be important because some monotherapy advocates suggest this strategy may prove useful in low- and middle-income countries with fewer antiretrovirals in stock--and with few subtype B infections.
MONARK trial investigators reported in 2006 that fewer people randomized to lopinavir/ritonavir alone than to lopinavir-containing triple therapy had a viral load below 50 copies in a 48-week on-treatment analysis (56 of 67 or 84% versus 40 of 41 or 98%, P = 0.03) [2]. At the European AIDS Conference Philippe Flandre looked only at 53 monotherapy responders and 13 nonresponders to figure out why the novel strategy fell short of triple therapy [1].
Of the 66 people in this analysis, 46 (70%) had subtype B infection and 20 (30%) harbored another HIV-1 strain, usually CRF02_AG. Subtype-B infected people accounted for 6 monotherapy failures (13%) and 40 monotherapy responses (87%), while non-B-infected people accounted for 7 monotherapy failures (35%) and 13 responses (65%). Responders and nonresponders began lopinavir monotherapy with equivalent viral loads, averaging 4.38 and 4.54 log copies/mL. But by treatment week 1 the average load fell 1.07 log in responders versus only 0.54 log in nonresponders. At that point 8 responders (16%) and no nonresponders had fewer than 400 copies, and by the second week 25 responders (49%) and 2 nonresponders (15%) had a sub-400-copy load.
Multivariate analysis sifted out only two factors that independently bolstered the chance of responding: a sub-400 load by week 4 boosted chances of success 7.59 times (95% confidence interval [CI] 1.65 to 34.8, P = 0.01). And being infected with subtype B rather than another HIV-1 strain made success 6.36 times more likely (95% CI 1.4 to 28.9, P = 0.01).
However, 14 of 20 people with non-B virus (70%) had a viral load under 400 copies/mL at week 4, compared with 27 of 46 subtype B-infected people (59%). Indeed, the non-B group had a median week 4 viral load drop of 2.24 log versus 1.91 log in the subtype B group, a significant difference (P = 0.019). Those results suggest that non-B virus in itself did not predispose people to lopinavir monotherapy failure.
The non-B group was also younger (median 31 versus 40 years, P = 0.016), included more women (50% versus 17.4%, P = 0.014), and reported missing at least one dose in the last two visits more often than people harboring subtype B (40% versus 13%, P = 0.022). People with non-B HIV-1 reported worse adherence than people carrying subtype B at eight of nine follow-up visits.
The adherence findings suggest that infection with a non-B virus is a marker for social or economic factors that make it harder to take antiretrovirals--even monotherapy--consistently. The MONARK study took place in France, Germany, Italy, Poland, and Spain, where many people with non-B virus have emigrated from poorer countries and endure numerous economic and social disadvantages. Of course the same or similar socioeconomic deprivations may hold true among natives of poor African, Asian, or Eastern European countries. At the same time, one hesitates to read too much into these adherence results because they came from self-reports.
Flandre argued that the higher proportion of women in the non-B group did not contribute to the risk of monotherapy failure for pharmacologic reasons, such as attaining higher (possibly toxic) lopinavir/ritonavir levels because women usually weigh less than men.
References
1. Flandre P, Delaugerre C, Ghosn J, et al. Prognostic factors of virological success in antiretroviral-naive patients receiving LPV/r monotherapy in the MONARK trial. 11th European AIDS Conference. October 24-27, 2007. Madrid. Abstract PS1.2.
2. Delfraissy J-F, Flandre P, Delaugerre C, et al. MONARK Trial (MONotherapy AntiRetroviral Kaletra): 48-week analysis of lopinavir/ritonavir (LPV/r) monotherapy
compared to LPV/r + zidovudine/lamivudine in antiretroviral-naive patients. XVI International AIDS Conference. August 13-18, 2006. Toronto. Abstract THLB0202.
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