Transient increases in viral load are common among people on HAART, finds a study of UK patients
11 May 2002. Related: Antiretrovirals.
Graham McKerrow, HIV i-Base
Transient increases in viral load are common among patients for whom highly active antiretroviral therapy (HAART) has previously reduced their viral loads to fewer than 50 copies/mL, according to a study at the Royal Free Hospital in London.
Researchers found that 35% of the patients they studied had transient increases in their viral loads, most of them in the 50 to 400 copies/mL range.
For the majority of people studied, subsequent viral load estimations showed a return to fewer than 50 copies/mL. The researchers, led by Dr Antonia Moore, advise in the journal AIDS of 8 March 2002 that: “A single raised viral load should lead to adherence support and intensified monitoring. Subsequent treatment decisions can then be based on evidence of true virological rebound or failure.”
Dr Moore’s team at the Royal Free Centre for HIV Medicine followed a cohort of 553 patients on HAART with viral loads of fewer than 50 copies/mL from their first viral load of fewer than 50 copies/mL (in some cases this was when the ultrasensitive viral load assay first became available in the clinic) until their last viral load measurement or until they had experienced virological failure (two consecutive viral loads > 400 copies/mL).
Of the 553 patients studied, 207 (37%) had a viral load of fewer than 50 copies/mL measured within 48 weeks of starting their first HAART regimen, 79 (14%) between 48 and 72 weeks, 97 (18%) between 72 and 96 weeks, 86 (16%) between 96 and 120 weeks, and 84 (15%) after more than 120 weeks of treatment.
The majority of patients, 326 (66%), were taking three-drug combinations, although 45 (8%) were on more than five drugs. The median follow-up time was 56 weeks (range 4-174 weeks). A total of 192 patients (35%) experienced at least one viral load measurement over 50 copies/mL during the period of study, whereas 42 (8%) experienced virological failure as defined above. Of the 192 patients with a value of more than 50 copies/mL recorded, 40% had values of more than 200 copies/mL.
The researchers report that those who had ever used more than four drugs were significantly more likely to experience both a transient increase in viral load and virological failure than those who had used four or fewer antiretroviral agents (P < 0.0001 and P = 0.004, respectively).
In their conclusion, Dr Moore and colleagues write: “In our cohort it appears that those with an initial raised value of over 400 copies/mL are more likely to have a sustained increase and become virological failures, whereas those with a first raised value of between 50 and 400 copies/mL have a follow-up of less than 50 copies/mL in the majority of cases and over 400 copies/mL in under 10% of cases. Both ‘blips’ and virological failure were found to be more common in those patients with greater drug experience.”
The explanation behind the increase in viral load is often established only in retrospect, they report, but a single raised value may be the result of intercurrent infection or vaccination, which may be associated with a transient increase in viral load [2, 3].
Other transient increases may be the result of the emergence of drug resistance, but as shown in the study of Cohen Stuart et al [4], in the short term, this does not necessarily translate into virological failure. Many such apparent increases could be caused by assay variability.
In common with others [5], Dr Moore and colleagues found that two consecutive values of 50-400 copies/mL are likely to be followed by a value of less than 50 copies/mL in approximately half the cases, and by a value of over 400 copies/mL in less than 10% of cases.
The authors write: “In the context of any apparent increase in viral load, the importance of adherence must be reiterated [6], and the patient’s drug combination must be assessed to evaluate the possibility of drug interactions, leading to subtherapeutic levels of antiretroviral drugs and the possible emergence of resistant virus.
“As our results have shown, the majority of first viral load values over 50 copies/mL do not signal treatment failure, and are more likely to turn out to be ‘transient’ increases. This finding may not be the result of a spontaneous reduction to less than 50 copies/mL, and is possibly the result of improved patient adherence when faced with the potential threat of treatment failure.
“A single increased viral load measurement should lead to adherence support and intensified monitoring of the patient in order that subsequent treatment decisions can be based on evidence of true virological rebound or failure,” the authors advise.
Comment
Although patients in this cohort study were receiving HAART it is unclear if this included both protease inhibitor and NNRTI based combinations (or indeed triple nucleoside analogue combination). The significance of a single increased viral load measurement may be expected to be of greater significance in NNRTI based combinations due to the low genetic barrier to resistance that these agents present. Further analysis in terms of class of combination would appear warranted.
References:
- Moore AL, Youle M, Lipman M et al. Raised viral load in patients with viral suppression on highly active antiretroviral therapy: transient increase or treatment failure? AIDS 2002 Mar 8;16(4):615-8
- Gunthard HF, Wong JK, Spina CA et al. Effects of influenza vaccination on viral replication and immune response in persons infected with human immunodeficiency virus receiving potent antiretroviral therapy. J Infect Dis 2000, 181:522-531
- King Jr JC, Treanor J, Fast PE et al. Comparison of the safety, vaccine virus shedding and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults. J Inf Dis 2000, 81:725-728.
- Cohen Stuart JWT, Wensing AMJ, Kovacs C et al. Transient relapses (‘blips’) of plasma HIV RNA levels during HAART are associated with drug resistance. J Acquir Immune Defic Syndr 2001, 28:105-113.
- Greub C, Cozzi-Lepri A, Staszewski S et al. Swiss and Frankfurt cohorts. Low level HIV viral rebound and blips in patients receiving potent antiretroviral therapy. In: 8th Annual Conference on Retroviruses. Chicago, 4-8 February 2000 [Abstract 522].
- Paterson DL, Swindells S, Mohr J et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000, 133:21-20.