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Incorrect attribution of cerebrospinal fluid HIV-1 virological escape and lymphocytic meningitis to lopinavir/ritonavir monotherapy

Perez-Valero, Ignacioa; Zamora, Francisco Xaviera; Pulido, Federicob; Arribas, Jose Ra

doi: 10.1097/QAD.0b013e32833d56a5

aHIV Unit, Internal Medicine Service, Hospital La Paz, IdiPAZ (Hospital La Paz Health Research Institute), Spain

bHIV Unit, Hospital 12 de Octubre, Madrid, Spain.

Received 14 June, 2010

Accepted 17 June, 2010

We respectfully disagree with many of the interpretations of the case reported by de Truchis et al. [1] entitled ‘Cerebrospinal fluid HIV-1 virological escape with lymphocytic meningitis under lopinavir/ritonavir monotherapy’.

The title is misleading. Many readers might interpret that ‘escape’ means that HIV replication was suppressed in blood and active in the cerebrospinal fluid (CSF). This is not the case as the patient at the time of presentation had active replication both in blood and CSF.

The patient was inadequately treated with lopinavir/ritonavir monotherapy. Authors do not emphasize enough that, as recommended in the European AIDS Clinical Society (EACS) guidelines [2], patients infected with protease inhibitor-resistant isolates should not be treated with lopinavir/ritonavir monotherapy. All the trials of protease inhibitor monotherapy have excluded patients who might be infected with HIV isolates resistant to protease inhibitors. It is interesting, however, that in Truchis et al. [1] case, virological suppression was achieved during 18 months despite intermediate resistance to lopinavir/ritonavir. Once again, this finding supports the extremely high genetic barrier to resistance of boosted protease inhibitors.

Virological failure and lymphocytic meningitis is wrongly attributed to the use of lopinavir/ritonavir monotherapy. It is very likely that the reduction of plasmatic and CSF levels of lopinavir/ritonavir concentrations possibly caused by orlistat would have not changed if the patient had been treated with two analogs and lopinavir/ritonavir with similar clinical consequences and with the additional possible development of resistance to nucleosides.

The authors claim discordant viral evolution in CSF without adequate data. There is no CSF sample to prove that an isolate with 54V was also present in CSF at the time the first resistance testing was performed in plasma. An alternative explanation is disappearance of 54V both in plasma and CSF owing to insufficient drug pressure caused by low levels of lopinavir/ritonavir. Nevertheless, discordant viral evolution in the CSF and higher viral loads in CSF than in plasma have also been described in patients receiving triple therapy [3].

The authors incorrectly quote Monotherapy Switzerland Thailand (MOST) study of Gutmann et al. [4] as supporting evidence of a higher risk of discordant replication in CSF in patients treated with boosted protease inhibitor monotherapy. In the MOST study, all six patients with neurological symptoms had virological failure both in blood and CSF.

The authors mention the studies of Gutmann et al. [4] and Katlama et al. [5] as evidence of a higher risk of HIV encephalitis in patients treated with monotherapy but omit to mention that this complication also occurs in patients treated with triple therapy [3].

Until we have a randomized clinical trial that systematically evaluates CSF replication in patients treated with boosted protease inhibitor monotherapy versus triple therapy, claims of ‘a higher risk of virological escape under protease inhibitor monotherapy’ would not be based on adequate evidence. Finally, we recommend that clinicians closely follow the EACS guidelines [2] before switching patients to boosted protease inhibitor monotherapy.

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1. de Truchis P, Mathez D, Abe E, Dinh A, Ledu D, Greder-Belan A, Alvarez JC. Cerebrospinal fluid HIV-1 virological escape with lymphocytic meningitis under lopinavir/ritonavir monotherapy. AIDS 2010; 24:1235–1236.
2. Clumeck N, Dedes N, Pozniak A, Raffi F, and the EACS Executive Committee. Clinical management and treatment of HIV infected adults in Europe 2009. [Accessed 14 June 2010]
3. Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 2010; 50:773–778.
4. Gutmann C, Opravil M, Yerly S, Fux C, Furrer H, Cavassini M, et al. Swiss HIV Cohort. low nadir CD4 cell count predicts failure of monotherapy maintenance with ritonavir-boosted lopinavir: results after premature termination of a randomized study due to unexpected high failure rate in the monotherapy arm [abstract #578]. In: Program and Abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; 8–11 February 2009; Montreal, Canada.
5. Katlama C, Valentin MA, Algarte-Genin M, Duvivier C, Lambert-Nicot S, Girard PM, et al. Efficacy of darunavir/ritonavir as single-drug maintenance therapy in patients with HIV-1 viral suppression: a randomized open-label non inferiority trial, MONOI-ANRS 136. In: Program and Abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 19–22 July 2009; Cape Town, South Africa. p. 3689.
© 2010 Lippincott Williams & Wilkins, Inc.