Open Access Research article

Rate and determinants of treatment response to different antiretroviral combination strategies in subjects presenting at HIV-1 diagnosis with advanced disease

Antonella Esposito1, Marco Floridia2, Gabriella d'Ettorre3, Daniele Pastori4, Alessandra Fantauzzi1, Paola Massetti3, Giancarlo Ceccarelli3, Camilla Ajassa3, Vincenzo Vullo3 and Ivano Mezzaroma1*

Author Affiliations

1 Dpt. of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy

2 Dpt. of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy

3 Dpt. of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy

4 Dpt. of Internal Medicine and Medical Specialties, "Sapienza" University of Rome, Rome, Italy

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BMC Infectious Diseases 2011, 11:341  doi:10.1186/1471-2334-11-341

Published: 14 December 2011

Abstract

Background

The optimal therapeutic strategies for patients presenting with advanced disease at HIV-1 diagnosis are as yet incompletely defined.

Methods

All patients presenting at two outpatient clinics in 2000-2009 with an AIDS-defining clinical condition or a CD4+ T cell count < 200/μL at HIV-1 diagnosis were analyzed for the presence of combined immunovirological response, defined by the concomitant presence of an absolute number of CD4+ T cells > 200 cells/μL and a plasma HIV-1 RNA copy number < 50/mL after 12 months of HAART.

Results

Among 102 evaluable patients, first-line regimens were protease inhibitors [PI]-based in 78 cases (77%) and efavirenz-based in 24 cases (23%). The overall response rate was 65% (95% CI: 55-74), with no differences by gender, age, nationality, route of transmission, hepatitis virus coinfections, presence of AIDS-defining clinical events, baseline HIV-1 viral load, or type of regimen (response rates with PI-based and efavirenz-based therapy: 63% and 71%, respectively, p = 0.474). Response rate was significantly better with higher baseline CD4+ T cell counts (78% with CD4+ ≥ 100/μL, compared to 50% with CD4+ < 100/μL; odds ratio: 3.5; 95% CI: 1.49-8.23, p = 0.003). Median time on first-line antiretroviral therapy was 24 months (interquartile range: 12-48). Switch to a second line treatment occurred in 57% of patients, mainly for simplification (57%), and was significantly more common with PI-based regimens [adjusted hazard ratios (AHR) with respect to efavirenz-based regimens: 3.88 for unboosted PIs (95% CI: 1.40-10.7, p = 0.009) and 4.21 for ritonavir-boosted PI (95%CI 1.7-10.4, p = 0.002)] and in older subjects (≥ 50 years) (AHR: 1.83; 95% CI: 1.02-3.31, p = 0.044). Overall mortality was low (3% after a median follow up of 48 months).

Conclusions

Our data indicate that a favorable immunovirological response is possible in the majority of naive patients presenting at HIV-1 diagnosis with AIDS or low CD4+ T cell counts, and confirm that starting HAART with a more compromised immune system may be associated with a delayed and sometimes partial immune recovery. Simpler regimens may be preferable in this particular population.