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≤1,000 copies/ml 24 weeks after CART discontinuation.
Methods
We estimated the prevalence of VL ≤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.
Results and discussion
The prevalence of VL ≤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≤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.
References
1.
FidlerS., OxeniusA., BradyM.Virological and immunological effects of short-course antiretroviral therapy in primary HIV infection.AIDS2002; 16: 2049–2054.
2.
SmithD.E., WalkerB.D., CooperD.A., RosenbergE.S., KaldorJ.M.Is antiretroviral treatment of primary infection clinically justified on the basis of current evidence?AIDS2004; 18: 709–718.
3.
Kinloch-de LoesS., HoenB., SmithD.E.Impact of therapeutic immunisation on HIV-1 viremia after discontinuation of antiretroviral therapy initiated during acute infection.J Infect Dis2005; 192: 607–617.
4.
CASCADE Collaboration.Changes in the uptake of antiretroviral therapy and survival in people with known duration of HIV infection in Europe: results from CASCADE.HIV Med2000; 1: 224–231.
5.
KinlochS., CooperD., LampeF.The Quest cohort: treatment of primary HIV infection with quadruple CART: week 48 preliminary results [abstract 520].In Program and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections (Boston, MA, USA).Alexandria, VA, USA: Foundation for Retrovirology and Human Health, 2003: 240.
6.
HubertJ., BurgardM., DussaixE.Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection.AIDS2000; 14: 123–131.
7.
LylesC.M., DorrucciM., VlahovS.Longitudinal human immunodeficiency virus type 1 load in the Italian Seroconversion Study: correlates and temporal trends of virus load.J Infect Dis1999; 180: 1018–1024.
8.
SterlingT.R., LylesC.M., VlahovD., AstemborskiJ., MargolickJ.B., QuinnT.C.Sex differences in longitudinal Human Immunodeficiency Virus type 1 RNA levels among seroconverters.J Infect Dis1999; 180: 666–672.
9.
TouloumiG., PantazisN., BabikerA.G.Differences in HIV-RNA levels before the initiation of antiretroviral therapy among 1864 individuals with known HIV-1 seroconversion dates.AIDS2004; 18: 1697–1705.
10.
PantazisN., TouloumiG., WalkerA.S., BabikerA.G.Bivariate modelling of longitudinal measurements of two human immunodeficiency type 1 disease progression markers in the presence of informative drop-outs.Appl Statist2005; 54: 405–423.
11.
DesquilbetL., GoujardC., RouziouxC.Does transient CART during primary infection lower the virological set-point?AIDS2004; 18: 2361–2369.
12.
MadecY., BoufassaF., PorterK., MeyerL. CASCADE Collaboration. Spontaneous control of viral load and CD4 cell count progression among HIV-1 seroconverters.AIDS2005; 19: 2001–2007.
13.
VanhemsP., LambertJ., CooperD.A.Severity and prognosis of acute Human Immunodeficiency Virus type 1 illness: a dose-response relationship.Clin Infect Dis1998; 26: 323–329.
14.
RosenbergE.S., AltfeldM., PoonS.H.Immune control of HIV-1 after early treatment of acute infection.Nature2000; 407: 523–526.
15.
GirardP.M., SchneiderV., DeheeA.Treatment interruption after one year of triple nucleoside analogue therapy for primary HIV infection.AIDS2001; 15: 275–277.
16.
MarkowitzM., JinX., HurleyA.Discontinuation of antiretroviral therapy commenced early during the course of human immunodeficiency virus type 1 infection, with or without adjunctive vaccination.J Infect Dis2002; 186: 634–643.
17.
HoenB., FournierI., LacabaratzC.PRIMSTOP Study Group. Structured treatment interruptions in primary HIV-1 infection - The ANRS 100 PRIMSTOP Trial.JAIDS2005; 40: 307–316.
