Research Article: Long-term treatment outcomes of ritonavir-boosted lopinavir monotherapy among HIV-infected patients who experienced NRTI and NNRTI failure

Date Published: March 13, 2012

Publisher: BioMed Central

Author(s): Weerawat Manosuthi, Supeda Thongyen, Samruay Nilkamhang, Sukanya Manosuthi, Somnuek Sungkanuparph.

http://doi.org/10.1186/1742-6405-9-8

Abstract

We continue the previously described prospective cohort study of ritonovir-boosted lopinavir (LPV/r) monotherapy for second-line therapy in HIV-infected patients with prior failure and extensive resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), with the objective being to determine the three-year treatment responses.

There were 40 patients with a mean ± SD age of 37 ± 8 years. Median (IQR) baseline CD4 was 123 (37-245) cells/mm3 and median (IQR) HIV-1 RNA was 55,800 (9,670-100,000) copies/mL. All patients received twice daily LPV/r 400/100 mg and recycled lamivudine 150 mg. By intend-to-treat analysis at 144 weeks, 26 (65%) and 22 (56%) patients achieved HIV-1 RNA at < 400 and < 50 copies/mL, respectively. In as-treated analysis, the corresponding rates were 26 of 28 (93%) and 22 of 28 (78%), respectively. Low-level viral rebound (HIV-1 RNA 50-400 copies/mL) was found in 6 (15%), 6 (15%), and 4 (10%) patients at week 48, 96 and week 144, respectively. Medians CD4 at week 48, 96, and 144 were 351, 481, and 584 cells/mm3 and significantly changed from baseline (all, P < 0.05). There were increments of mean triglycerides at 48 weeks and 144 weeks from baseline (P < 0.05). No major protease resistance-associated mutations emerged after virologic failure. LPV/r monotherapy with recycled lamivudine can maintain long-term virologic suppression in a relatively small proportion of patients failing NNRTI-based regimen and having limit option for active NRTI. More antiretroviral classes are needed be accessible in resource-limited countries.

Partial Text

There are many concerns raised regarding boosted protease inhibitor monotherapy in HIV treatment include this strategic treatment may not be as effective as other combined antiretroviral therapies (ART), high rate of low-level viremia and may lead to developing treatment failure, and a higher level of adherence is required than with the use of standard combined ART [1]. In addition, there is an important concern about the ability of monotherapy to penetrate viral reservoirs and prevent viral replication in sanctuary sites, such as genital tract and central nervous system. Studies evaluating ritonavir-boosted protease inhibitor monotherapy that derived from the western countries have been studied in three patient settings including initial treatment, induction-maintenance, and simplification monotherapy after patients have been virologically suppressed – all are in patients without treatment failure [2]. However, data regarding durability of this strategic treatment is still scanty, owing to supporting by only relatively short-term data. On the other hand, HIV is often resistant to most existing nucleoside reverse transcriptase inhibitors (NRTIs) and non- nucleoside reverse transcriptase inhibitors (NNRTIs) among patients who have failed with the first regimen in resource-constrained settings, secondary to the delayed detection of treatment failure. Therefore, constructing the next antiretroviral regimens that combined three fully active drugs for HIV-infected patients with prior failure and extensive resistance to NRTIs and NNRTIs in such setting is often impossible. Therefore, we conducted a prospective cohort study of ritonavir-boosted lopinavir monotherapy for the second-line therapy in HIV-1 infected patients who failed antiretroviral regimens containing NRTIs and NNRTI as previously described [3]. In the present analysis, we continued the prospective cohort study with the objectives to determine the three-year virologic and immunologic responses, and lipid derangements.

The authors declare that they have no competing interests.

WM participated in the design of the study, statistical analysis and draft the manuscript. ST, SN, SM, and SS participated in the design of the study and draft the manuscript. All authors read and approved the final manuscript.

 

Source:

http://doi.org/10.1186/1742-6405-9-8

 

Leave a Reply

Your email address will not be published.