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Tell me how this news could be Good?
Aug 6, 2003

Dr. Wohl,

You as Doctor "Feel Good" may perhaps have the ability to explain why this news could be good? I have looked at it over three times and really see many negative things but find it hard to find the good points. Please tell me what could be could.

Andrew Jackson

HIV Rebound After Suppression on HAART

Patients on HAART generally respond with a rapid reduction in plasma HIV viral load. The median time to achieving HIV undetectable levels is approximately 4 months. It is widely believed that achieving and maintaining prolonged HIV suppression is directly related to the long-term efficacy of HAART.

However, the viral load may start to rise in a substantial proportion of patients. This event could be due to adverse events, the emergence of drug-resistant virus, the difficulties of adherence, and/or the limited number of available drugs.

Few studies have evaluated the long-term response to HAART and even fewer have investigated the reasons for HIV rebound.

The purpose of the current multicenter European study was to determine the rate of virological rebound and the factors associated with rebound among patients on HAART with previously undetectable HIV levels. The results of the study appear in the August 15, 2003 issue of AIDS. A cohort of 2444 patients from the EuroSIDA study formed the patient population for this observational study. Patients were followed from their first viral load under 400 copies/ml to the first of two consecutive viral loads above 400 copies/ml. Incidence rates were calculated using person-years of follow-up (PYFU), Cox proportional hazards models were used to determine factors related to rebound.

Of 2444 patients, 1031 experienced virological rebound (42.2). The incidence of rebound decreased over time; from 33.5 in the first 6 months after initial suppression to 8.6 per 100 PYFU at 2 years after initial suppression (P < 0.0001). The rate of rebound was lower for treatment-naive compared with treatment-experienced patients. In multivariate models, patients who changed treatment were more likely to rebound, as were patients with higher viral loads on starting HAART. Treatment-naive patients were less likely to rebound. Among pretreated patients, those who were started on new nucleosides were less likely to rebound.

The authors conclude, The rate of virological rebound decreased over time, suggesting that the greatest risk of treatment failure is in the months after initial suppression. Treatment-naive patients were at a lower risk of rebound, but among drug-experienced patients, those who added new nucleosides had a lower risk of rebound, as were patients with a good immunological response. Commentary His study found a substantial number of patients who had a rebound in viral load after initial virological suppression on HAART regimens, but the rate of virological rebound decreased over time, suggesting that if the viral load does not rebound in the initial months after virological suppression, there is less risk of virological rebound over time as the time from suppression increases. Whereas treatment-naive patients had the lowest risk of virological rebound, treatment-experienced patients who could add new antiretroviral drugs to their HAART regimen were also significantly less likely to experience virological rebound than those who did not add new antiretroviral drugs to their HAART regimen.

Patients on more intensive antiviral treatment regimens were significantly more likely to have a rebound in viral load, which could be partly explained by compliance or side effects. Patients who swapped any drug in their HAART regimen were also more likely to experience virological rebound.

There is conflicting evidence on the importance of low levels of viral rebound, or 'blips' on long term virological suppression , although these results may suggest that it is important, in terms of virological rebound, to achieve the lowest possible levels of viremia.

It is also interesting to note that, among treatment-experienced patients, those who could add new drugs to their HAART regimen were significantly less likely to have a rebound in viral load.

Patients taking NNRTI were more likely to experience virological rebound. The majority of patients were taking nevirapine as their first NNRTI-containing HAART regimen. Several observational studies, including EuroSIDA, have reported a superior virological response to HAART in efavirenz-containing regimens compared with nevirapine , both in naive and treatment-experienced patients. However, the results of the 2NN trial showed no difference in the virologic response to these two drugs.

In summary, the authors note We found a higher rate of virological rebound in treatment-experienced patients compared with treatment-naive patients, and a decrease in the rate of virological rebound over time. The long term follow-up of large cohorts such as EuroSIDA is essential to monitor whether virological rebound eventually results in immunological failure and subsequent clinical failure.


Reference A Mocroft and others (; for the EuroSIDA study group). Virological rebound after suppression on highly active antiretroviral therapy. AIDS 17(12): 1741-1751. August 15, 2003.

Response from Dr. Wohl

Well a 42% rate of treatment failure is not good. However, it is important to note that this study included a mixed bag of patients: those on first line therapy, salvage treatment, deep salvage; on a variety of different combinations and with a host of different levels of adherence, mental illnesses, baseline viral loads/CD4 cell counts and other factors that influence response to and tolerability of HIV therapy.

This is 'real world' but it is hard to hold any one individual up to this and say your chance of failing your regimen (or your regimen failing you) is 42%.

The relatively good news is that this supports the first shot is your best shot idea, that is your first regimen is likely to be the most effective, so make it good. Also, failure was most likely to occur early during therapy. Clinicans and patients need to be vigilant during the first weeks to months of a regimen for signs of toxicity and suboptimal viral response. As therapies increase in potency and convenience and become more tolerable the rate of success, I believe, will climb. DW

Enroll in a clinical Trial Like Me...Please Post!!!!

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