Treatment history and baseline viral load, but not viral tropism or CCR-5 genotype, influence prolonged antiviral efficacy of highly active antiretroviral treatment.
BACKGROUND
The efficacy of highly active antiretroviral treatment (HAART) in HIV-1 disease may vary between nucleoside-naive and experienced patients as well as between patients with different viral phenotypes and in different stages of disease.


OBJECTIVE
To investigate variables of importance for successful long-term viral suppression by analysing virological, clinical and immunological characteristics at initiation of protease inhibitor treatment on suppression of HIV RNA over 1 year.


METHODS
An open, non-randomized, observational clinical study.


METHODS
Venhälsan, Department of Dermatovenereology, Söder Hospital, Stockholm, Sweden.


METHODS
A total of 147 unselected advanced patients with known HIV-1 infection for a mean of 7 years, of whom 37% had AIDS and who started treatment with a protease inhibitor during 1996.


METHODS
All patients received HAART with at least two nucleoside analogues in combination with either indinavir (81%) or ritonavir (19%). The majority (77%) had been previously treated with nucleoside analogues for a mean of 39 months.


METHODS
CD4+ lymphocyte count, plasma HIV-1 RNA, viral phenotype and HIV-1 coreceptor CCR-5 genotype at baseline. Viral load and CD4+ lymphocyte count were determined every 3 months.


RESULTS
Patients were analysed on an intention-to-treat basis. The mean CD4+ lymphocyte count at baseline was 170 x 10(6)/l and the median viral load was 68 600 copies/ml. Heterozygosity for the delta32 deletion of the CCR-5 gene (delta32/wt) was found in 27%. MT-2 positive virus (syncytium-inducing) was isolated in 46%. Logistic regression revealed that nucleoside analogue experience and baseline log10 HIV-1 RNA were the only factors independently related to plasma HIV-1 RNA levels below 500 copies/ml after 1 year of treatment, which was found in 69%.


CONCLUSIONS
The virological outcome after 1 year of HAART was strongly correlated to prior treatment history and baseline viral load, whereas CD4+ lymphocyte count, CCR-5 genotype and viral biological phenotype had less influence. The long-term antiviral efficacy of HAART was lowest in individuals with previous nucleoside analogue treatment and a high baseline viral load. In these individuals an even more aggressive treatment should be considered.
Bratt
G
G
Department of Dermatovenereology (Venhälsan), Södersjukhuset, Stockholm, Sweden.
Karlsson
A
A
Leandersson
A C
AC
Albert
J
J
Wahren
B
B
Sandström
E
E
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011480:Protease Inhibitors / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D018523:Tropism; D019562:Viral Load
D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D012367:RNA, Viral