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. RESULTS AND DISCUSSION: 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.
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. RESULTS AND DISCUSSION: 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.
Authors: Christine M Hogan; Victor Degruttola; Xin Sun; Susan A Fiscus; Carlos Del Rio; C Bradley Hare; Martin Markowitz; Elizabeth Connick; Bernard Macatangay; Karen T Tashima; Beatrice Kallungal; Rob Camp; Tia Morton; Eric S Daar; Susan Little Journal: J Infect Dis Date: 2011-12-15 Impact factor: 5.226
Authors: M Kumi Smith; Sarah E Rutstein; Kimberly A Powers; Sarah Fidler; William C Miller; Joseph J Eron; Myron S Cohen Journal: J Acquir Immune Defic Syndr Date: 2013-07 Impact factor: 3.731
Authors: Viktor von Wyl; Sara Gianella; Marek Fischer; Barbara Niederoest; Herbert Kuster; Manuel Battegay; Enos Bernasconi; Matthias Cavassini; Andri Rauch; Bernard Hirschel; Pietro Vernazza; Rainer Weber; Beda Joos; Huldrych F Günthard Journal: PLoS One Date: 2011-11-15 Impact factor: 3.240
Authors: Genevieve E Martin; Morgane Gossez; James P Williams; Wolfgang Stöhr; Jodi Meyerowitz; Ellen M Leitman; Philip Goulder; Kholoud Porter; Sarah Fidler; John Frater Journal: AIDS Date: 2017-02-20 Impact factor: 4.177