Effect of transient antiretroviral treatment during acute HIV infection: comparison of the Quest trial results with CASCADE natural history study.
OBJECTIVE
The benefit of transient combination antiretroviral treatment (CART) during acute HIV infection is uncertain. We used the seroconverter database CASCADE to provide a historical comparison for the Quest trial, in which 79 subjects with acute HIV infection received CART for an average of 2.6 years, and 17.7% (95% confidence interval [CI]: 10.9-27.6) fulfilled the primary endpoint of VL < or =1,000 copies/ml 24 weeks after CART discontinuation.


METHODS
We estimated the prevalence of VL < or =1,000 copies/ml three years after seroconversion and prior to any ART among 385 sexually infected subjects in CASCADE who seroconverted between 1988 and 1996. We conducted a pre-specified comparison with the recently published Quest results, and considered potential biases.


CONCLUSIONS
The prevalence of VL < or =1,000 copies/ml at year three in CASCADE was 10.1% (95% CI: 7.5-13.5) (absolute difference compared to 17.7% in Quest: 7.6%; 95% CI: -0.1-17.8; P=0.053). In CASCADE, VL < or =1,000 copies/ml was less common among homosexual and heterosexual men compared with women (8.5%, 7.3% and 17.6% respectively) and in subjects with symptomatic infection compared with those without (6.2% and 12.6%, respectively). As Quest had a much greater proportion of symptomatic subjects than CASCADE, any true difference in VL might be underestimated. Therefore this comparison suggests that transient CART in acute infection might result in a modest increase in the probability of low VL subsequently. However, several factors mitigate this conclusion. First, this historical comparison might be subject to other unmeasured confounders. Second, a comparison of median VL at the same time point was not significant (4.02 copies/ml and 4.20 copies/ml in Quest and CASCADE, respectively; P=0.55). Finally, additional analysis suggested that the observed difference in low VL at year three would be consistent with an immediate effect of CART only - a delay of usual VL decline without additional benefit.


CONCLUSIONS
A small but significant proportion of seroconverters have low VL without ART. Transient CART in acute infection might increase the probability of low VL after treatment discontinuation, but such an effect is likely to be modest, and might represent a delay of natural history rather than a long-term therapeutic benefit.
Lampe
Fiona C
FC
Royal Free Centre for HIV Medicine, Royal Free and University College Medical School, London, UK. f.lampe@pops.ucl.ac.uk
Porter
Kholoud
K
Kaldor
John
J
Law
Matthew
M
Kinloch-de Loes
Sabine
S
Phillips
Andrew N
AN
D000208:Acute Disease; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006679:HIV Seropositivity; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents