Quantification of HIV-1 viral load in lymphoid and blood cells: assessment during four-drug combination therapy.
OBJECTIVE
To assess the antiretroviral effect of a combination of zidovudine, didanosine, lamivudine and saquinavir in plasma, peripheral blood mononuclear cells (PBMC) and lymph-node mononuclear cells (LNMC) after 8 weeks.


METHODS
Ten HIV-1 antiretroviral therapy-naive patients were given a combination of oral zidovudine (200 mg three times daily), oral didanosine (200 twice a day), oral lamivudine (150 mg twice a day) and oral saquinavir (600 mg three times daily). HIV-1 plasma RNA was measured by quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR). Infectious HIV-1 in PBMC and LNMC was measured by a coculture technique. HIV-1 RNA in PBMC and LNMC was quantified by RT-PCR. Proviral DNA titres in PBMC and LNMC were measured by endpoint dilution PCR. CD4 T-cells were analysed by flow cytometry.


RESULTS
CD4 cell counts rose in all patients (mean increase of 125 +/- 71 CD4 cells x 10(6)/l) and the benefit was greater for patients with fewer than 350 CD4 cells x 10(6)/l (mean increase of 159 +/- 74 CD4 cells x 10(6)/l). Plasma HIV-1 RNA decreased exponentially in all patients (mean decrease of 3.1 log10 after 8 weeks with a mean half-life of 2.2 +/- 0.6 days). HIV-1 RNA showed a decrease of 3.07 log10 in PBMC and of 2.1 log10 in LNMC. The decrease in plasma HIV-1 RNA was consistently associated with the decrease in LNMC. These data were supported by a concomitant drop of HIV-1 infectious titres in PBMC (mean decrease of 1.41 log10) and in LNMC (mean decrease of 2.54 log).


CONCLUSIONS
These data show a significant antiretroviral effect of this four-drug combination in blood and lymphoid tissues. However, a greater decrease in HIV-1 RNA was observed in PBMC and in plasma than in lymph node cells.
Tamalet
C
C
Laboratory of Virology, Timone Hospital, Marseille, France.
Lafeuillade
A
A
Fantini
J
J
Poggi
C
C
Yahi
N
N
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral; D016049:Didanosine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D019258:Saquinavir / Q000008:administration & dosage; D019562:Viral Load; D014766:Viremia / Q000821:virology; D015215:Zidovudine / Q000008:administration & dosage
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D016049:Didanosine; D019258:Saquinavir