HIV-1 induction-maintenance at the lymph node level: the "Apollo-97" Study.
OBJECTIVE
To assess the effects of five-drug combination therapy on HIV-1 load in lymph nodes and subsequent maintenance with four and three drugs.


METHODS
Ten pharmacotherapeutically naive patients received a combination of zidovudine, lamivudine, didanosine, ritonavir, and saquinavir for 24 weeks, then zidovudine, lamivudine, didanosine, and saquinavir for the next 24 weeks, and finally zidovudine, lamivudine, and saquinavir for the last 24 weeks. HIV-1 RNA in lymph nodes was measured using quantitative polymerase chain reaction (PCR) at baseline, after 12, 24, 48, and 78 weeks. Plasma HIV-1 RNA, proviral DNA in peripheral blood mononuclear cells (PBMCs), circulating lymphocyte subsets, and protease inhibitor levels in blood were also regularly measured. Genotypic resistance was assessed in the different compartments in 2 patients who were failed by therapy.


RESULTS
HIV-1 RNA decreased in lymph nodes in 9 patients and was stable in 1 despite initial control of plasma replication <20 copies/ml in each patient. Lymph node levels rebounded in 1 patient at week 72 as a result of lack of adherence and remained stable in the 8 others despite maintenance regimens. This represents a mean drop of -3.17 log in lymph nodes for the 8 patients maintaining undetectable viremia at 72 weeks. In the patient with stable lymph node viral RNA, selection of the M184V mutation was demonstrated at this level before detection in plasma and low blood saquinavir levels were found throughout the study. Continuous improvements in immune parameters were observed in all cases, although PBMC proviral DNA levels either showed a continuous decrease or stabilized to a plateau.


CONCLUSIONS
More complex regimens do not perform better in lymph nodes than classic triple therapy. The persistence of HIV-1 RNA in lymph nodes could be related with cellular resistance mechanisms rather than an insufficient potency of the regimens.
Lafeuillade
A
A
Department of Infectious Diseases, Laboratory of Virology, General Hospital, Toulon, France. avps@club-internet.fr
Poggi
C
C
Chadapaud
S
S
Hittinger
G
G
Chouraqui
M
M
Delbeke
E
E
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood / Q000302:isolation & purification*; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008198:Lymph Nodes / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008214:Lymphocytes / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000302:isolation & purification; D019438:Ritonavir / Q000627:therapeutic use; D019258:Saquinavir / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000503:physiopathology; D014779:Virus Replication
D019380:Anti-HIV Agents; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019259:Lamivudine; D016049:Didanosine; D019258:Saquinavir; D019438:Ritonavir