Efficacy of boosted protease inhibitor monotherapy in patients with complex medical problems : AIDS

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Research Letters

Efficacy of boosted protease inhibitor monotherapy in patients with complex medical problems

Garrett, Nigel J; Matin, Nasha; Edwards, Simon G; Miller, Robert F

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AIDS 21(13):p 1821-1823, August 20, 2007. | DOI: 10.1097/QAD.0b013e328270389b
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Although three-drug antiretroviral regimens are currently the recommended option for suppressing HIV [1], interest in a potential role for boosted protease inhibitor monotherapy (BPIm) has been generated by studies that have examined the efficacy of PI therapy in a variety of clinical settings [2–5]. Several randomised trials have shown comparable virological efficacy with lopinavir/ritonavir used as maintenance therapy following successful viral suppression with highly-active antiretroviral therapy (HAART) [4,5].

By contrast, few data exist on outcomes following initiation of BPIm among critically ill patients with acute medical problems in whom the benefits of using conventional HAART have to be balanced against the potential for causing life-threatening toxicity, drug–drug interactions and promotion of acquisition of resistance to HIV drugs [6].

At our centre between May 2004 and January 2007, we identified ten patients (five male), median (range) age = 43 (26–53) years, who presented with acute severe concurrent medical co-morbidity and who commenced BPIm at that presentation and continued it for greater than 2 weeks. Patients had a variety of acute medical problems (Table 1). Six were hospitalized for a prolonged period; median (range) = 44.5 (3–173) days. At initiation of BPIm, patients' median (range) CD4 count was 74 (0–530) cells/μl, and the HIV viral load was 92 200 (5300–279 600) copies/ml. Four patients had previously received HAART: four had acquired HIV drug resistance resulting from adherence problems (Table 1); another had anaphylaxis on two occasions following initiation of different antiretroviral combination therapies involving both nucleoside (NRTI) and non-nucleoside (NNRTI) reverse transcriptase inhibitor containing regimens, and a further patient (patient 2) had not taken HAART previously, but had multiple resistance mutations to both NRTI and NNRTI drugs.

Table 1:
Concurrent medical problems and laboratory results in ten HIV-infected patients started on boosted protease inhibitor monotherapy (BPIm).

All ten patients started lopinavir/ritonavir. One patient switched to atazanavir/ritonavir at day 10, because of gastrointestinal intolerance.

During follow-up (between 4 and 8 weeks) median (range) log10 HIV viral load reduction was 2.15 (1.62–3.1); in five patients, viral load was <400 copies/ml. Of the four patients who continued BPIm beyond 8 weeks, three had viral suppression after 52, 61 and 156 weeks, respectively. One had virological rebound after 48 weeks: new PI mutations (M46I, I54V and V82C) were identified. NRTI therapy was added in a further 4 patients after 8 weeks of BPIm, following resolution of the acute severe medical problems. Two patients were poorly adherent and discontinued antiretroviral therapy on hospital discharge. During follow-up, at median (range) 50 (8–156) weeks, no patient developed an opportunistic illness.

In this small non-controlled study, we have identified patients for who short term BPIm has been shown to be beneficial. Many clinicians would wait for resolution of an opportunistic infection prior to initiating antiretroviral therapy in most patients presenting with acute severe intercurrent illness. However, there are occasions when antiretroviral therapy is essential in the management of the underlying disease [6–8]. Furthermore, some pathology may be lifelong or has the potential to persist for an undefined period of time. Withholding antiretroviral therapy in these circumstances may leave the patient at ongoing risk of development of opportunistic infection. Decisions about the choice of HAART regimen may further be compromised by concerns that HAART may be interrupted due to intolerance, toxicity, drug–drug interaction or immune restoration syndrome. In these situations, BPIm provides an opportunity to control HIV viraemia and improve the immune system, with an attendant low risk of acquiring resistance should antiretroviral therapy be discontinued [9].

Of concern, one patient in this study acquired new PI resistance mutations after receiving BPIm for more than 1 year. This patient had multiple resistance mutations to NRTI- and NNRTI-based regimens, prior to starting BPIm.

The durability of BPIm as a treatment strategy remains uncertain. Evidence suggests that low-level viraemia (HIV-1 RNA 50–500 copies/ml) occurs more frequently in patients receiving BPIm [4] compared to patients receiving triple therapy. Furthermore, there are few data describing HIV viral replication in anatomic/pharmacologic sanctuary sites in patients receiving BPIm [10].

These preliminary data support the short-term use of BPIm in critically ill patients with contra-indications to institution of HAART. However, reports of low level viraemia and the uncertainty regarding drug penetration into sanctuary sites in patients on BPIm suggest close patient monitoring is needed, with consideration of augmentation of antiretroviral therapy, with introduction of NNRTI and or NRTI, on resolution of the critical illness.


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