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Compartmentalization of HIV-1 according to antiretroviral therapy: viral loads are correlated in blood and semen but poorly in blood and saliva

Bourlet, Thomas; Cazorla, Céline; Berthelot, Philippe; Grattard, Florence; Cognasse, Fabrice; Fresard, Anne; Defontaine, Christiane; Lucht, Fréderic R.; Genin, Christian; Pozzetto, Bruno

Research Letters

Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Faculty of Medicine J. Lisfranc, University of Saint-Etienne, France.

Sponsorship: This work was partly supported by a grant (96093) from the Agence Nationale de Recherches sur le SIDA.

Received: 10 August 2000;

revised: 19 October 2000; accepted: 31 October 2000.

Several investigators have recently shown interest in measuring the HIV-RNA level in different mucosal compartments, including seminal plasma [1–4] and saliva [1,4,5]. However, techniques are poorly standardized and range widely in sensitivity. In addition, whereas the quantification of HIV-1 in the semen and the impact of highly active antiretroviral therapy (ART) on the viral load of seminal plasma have been relatively well documented [6–9], similar features have not been studied so extensively in the saliva compartment.

A total of 46 sets of samples of blood, semen and saliva were taken on the same day from 40 HIV-1-infected men (aged 21–64 years) after written informed consent was obtained. Thirty-three of the men had been undergoing antiretroviral therapy for at least 3 months: with two and three drugs in 11 and 18 cases, respectively. The semen and saliva specimens were diluted (v/v) in phosphate buffered saline and centrifuged; all supernatants were stored at −80°C until use. Blood plasma HIV-RNA quantification was performed by the ultra-sensitive HIV-Monitor test (Roche Diagnostic Systems, Branchburg, NJ, USA). The RNA was extracted from mucosal samples by a modified silica-based protocol (QIAmp viral RNA kit; Qiagen, Chatsworth, CA, USA), and the quantitative reverse transcriptase–polymerase chain reaction was performed using the HIV-Monitor kit.

HIV-1 RNA was found to be positive in 37 out of 46 (80.4%) blood plasma, 17 out of 44 (38.6%) seminal plasma and 23 out of 45 (51.1%) saliva cell-free fractions; two semen and one saliva specimen(s) could not be quantified because of the presence of polymerase chain reaction inhibitors. Globally, the viral load was higher in blood than in the mucosal compartments (Table 1). However, four men exhibited a higher viral load in semen than in blood and another subject tested positive for HIV-1 RNA only in the saliva. A strong positive correlation was found between HIV-1-RNA loads in blood and seminal plasma (r S = 0.59, P < 0.0001), a weak correlation was found between blood and saliva (r S = 0.31, P < 0.05), but none was found between saliva and semen. The mean level of HIV RNA was significantly influenced by the number of antiviral drugs, both in the blood (P < 0.001) and seminal plasma (P < 0.05). Conversely, the viral load in saliva was poorly influenced by the intensity of ART. A couple of consecutive samples were available for six patients. In semen, the viral load decreased dramatically in four cases and remained undetectable in two cases, suggesting a great sensitivity of this compartment to ART, even when the therapy showed a poor efficacy in blood. Conversely, in saliva, the viral load collapsed only in the three patients receiving ART and exhibiting a decrease of more than two log10 of their blood viral load; in the three other patients, the viral load in the saliva was close to the value observed in the blood.

Table 1

Table 1

As shown by other authors [1,3], the viral loads were globally lower in mucosal samples than in blood. However, in a few cases, an opposite pattern was observed. A recent paper [3] focused on this subpopulation of HIV-infected patients with a high viral burden in the semen, frequently associated with a substantial viral shedding in the seminal cells and particularly at risk of the transmission of HIV via sexual activity. The level of correlation between blood and saliva HIV viral loads was shown to be much lower than between blood and semen, although still significant as reported previously [1,4,5]. This difference indicates that the compartmentalization of HIV, already discussed by others [1–3], is globally more marked for saliva than for semen. The absence of a correlation between viral loads in semen and saliva is an additional observation that strengthens this conclusion. To our knowledge, our study is the first to emphasize such a difference, by comparing prospectively the viral loads in the blood, semen and saliva in the same patients using the same technique. The latter finding is reinforced by the observation that antiviral treatment is highly efficient at decreasing the viral load in the semen but not in the saliva. The poor efficacy of antiviral drugs in reducing the viral load in the latter compartment, despite a relatively low amount of viral RNA in comparison with the semen or blood, was rather unpredictable. It could be the result of the reduced ability of antiviral drugs to spread in this fluid or a more rapid selection of resistant strains in this compartment. Although this finding needs further investigation, it is clear evidence for partial compartmentalization of HIV in the saliva.

Thomas Bourlet

Céline Cazorla

Philippe Berthelot

Florence Grattard

Fabrice Cognasse

Anne Fresard

Christiane Defontaine

Fréderic R. Lucht

Christian Genin

Bruno Pozzetto

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© 2001 Lippincott Williams & Wilkins, Inc.