Elsevier

Journal of Clinical Virology

Volume 64, March 2015, Pages 12-15
Journal of Clinical Virology

Short communication
Dolutegravir for the treatment of HIV-2 infection

https://doi.org/10.1016/j.jcv.2015.01.001Get rights and content

Highlights

  • Therapeutic options are limited for HIV-2 infection.

  • Dolutegravir is the most potent and latest approved HIV integrase inhibitor.

  • Two HIV-2+ patients with prior raltegravir failure and resistance experienced >1.5 log drop in plasma HIV-2 RNA with dolutegravir.

Abstract

Background

Therapeutic options are limited for HIV-2 infected persons, largely in part due to the lack of susceptibility to HIV-1 non-nucleoside reverse transcriptase inhibitors and poor susceptibility to some HIV-1 protease inhibitors. This is particularly worrisome for HIV-2 patients with prior antiretroviral failure.

Objectives

Report the virological response to dolutegravir in HIV-2-infected individuals.

Study design

Retrospective observational assessment of all HIV-2 individuals treated with dolutegravir in Spain.

Results

From 297 HIV-2-infected individuals recorded at the Spanish national registry, 26% received antiretroviral therapy. Six out of 8 failing on raltegravir selected for integrase resistance mutations N155H (4), Y143G (1) and Q148R (1). Two patients bearing N155H subsequently received dolutegravir. Both experienced initially more than 1.5 log drop in plasma HIV-2 RNA and significant CD4 gains. Whereas one kept on undetectable viremia 6 months later, the other experienced viral rebound.

Conclusion

Dolutegravir may be a good therapeutic option for patients with HIV-2 infection, including those that previously failed other integrase inhibitors.

Section snippets

Background

Human immunodeficiency virus type 2 (HIV-2) was first isolated in 1986. Being originated in West Africa following inter-species transmission from natural wildlife monkey reservoirs, the virus currently infects 1–2 million humans worldwide. Former Portuguese colonies abroad such as Mozambique, Goa (India) and Brazil are amongst the regions with a larger number of HIV-2 cases outside West Africa [1]. Although HIV-2 infection typically evolves with a prolonged asymptomatic period, a significant

Objectives

First report of clinical experience with dolutegravir in HIV-2 infected individuals.

Study design

We retrospectively assessed all HIV-2 individuals treated with dolutegravir in Spain. The integrase HIV-2 coding region was sequenced using an in-house nested-PCR protocol previously described [11] in plasma specimens collected from both raltegravir-naïve and raltegravir-experienced patients with detectable plasma HIV-2 RNA, all belonging to the Spanish HIV-2 cohort.

Mutations associated to raltegravir resistance were characterized and changes associated with dolutegravir resistance in HIV-1

Results

From 297 individuals recorded at the Spanish HIV-2 register up to the end of 2013, 196 (67%) were male and 212 (71%) were immigrants from Sub-Saharan Africa. At the time of diagnosis, 61% had undetectable plasma HIV-2 RNA. Other characteristics of this cohort have recently been reported elsewhere [13].

Overall, 26% of HIV-2 patients in Spain have received antiretroviral therapy. Despite being treated, 42% of them depicted less than 200CD4+ T-cells/mm3 42% at the last control. In contrast, CD4

Discussion

HIV-2 was firstly identified in 1986, examining patients presenting with AIDS and a negative/indeterminate HIV-1 serology [14]. Around 1–2 million people are estimated to be infected with HIV-2 worldwide. The most highly endemic regions are in West Africa and India, being France and Portugal the European countries with the largest number of HIV-2 infected individuals [1]. In Spain, nearly 300 individuals with HIV-2 infection have been reported so far [13].

HIV-2 is less pathogenic than HIV-1,

Competing interests

None.

Funding

This work was funded in part by grants from Instituto de Salud Carlos III (project nos. ICI14-00372, PI10/00520, CES12/003, PI13/01574) and Fundación Investigación y Educación en Sida (IES).

Ethical approval

This manuscript reports the clinical experience with two patients on routine clinical care.Given the retrospective nature of the observation, no specific ethical approval is requestedat my institution.

HIV-2 Spanish Study Group

C. Rodríguez and J. del Romero (Centro Sanitario Sandoval, Madrid); G. Marcaida, M.D. Ocete and T. Tuset (Hospital General Universitario, Valencia); E. Caballero and I. Molina (Hospital Vall d'Hebrón, Barcelona); A. Aguilera, J.J. Rodríguez-Calviño, D. Navarro and B. Regueiro (Hospital Conxo-CHUS, Santiago); R. Benito, J. Gil and M. Borrás (Hospital Clínico Universitario Lozano Blesa, Zaragoza); R. Ortiz de Lejarazu (Hospital Clínico Universitario, Valladolid); J.M. Eirós (Hospital Rio Hortega,

Acknowledgement

none

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