Abstract
Objective:Model trajectories of viral load measurements from time of starting combination antiretroviral therapy (cART), and use the model to predict whether patients will achieve suppressed viral load (≤200 copies/ml) within 6-months of starting cART.Design:Prospective cohort study including HIV-positive adults (UK Collaborative HIV Cohort Study).Methods:Eligible patients were antiretroviral naive and started cART after 1997. Random effects models were used to estimate viral load trends. Patients were randomly selected to form a validation dataset with those remaining used to fit the model. We evaluated predictions of suppression using indices of diagnostic test performance.Results:Of 9562 eligible patients 6435 were used to fit the model and 3127 for validation. Mean log10 viral load trajectories declined rapidly during the first 2 weeks post-cART, moderately between 2 weeks and 3 months, and more slowly thereafter. Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based cART-regimen predicted a steeper decline from 3 months onwards. Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits. Diagnostic performance improved when suppression was defined by two consecutive suppressed viral loads compared with one.Conclusions:Viral load measurements can be used to predict if a patient will be suppressed by 6-month post-cART. Graphical presentations of this information could help clinicians decide the optimum time to switch treatment regimen during the first months of cART.
Highlights
Combination antiretroviral therapy based on at least three antiretroviral drugs from at least two drug classes slows HIV replication and prevents transmission of HIV
Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based Combination antiretroviral therapy (cART)-regimen predicted a steeper decline from 3 months onwards
Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits
Summary
Combination antiretroviral therapy (cART) based on at least three antiretroviral drugs from at least two drug classes slows HIV replication and prevents transmission of HIV. During the first few weeks of treatment there is a rapid decline in viral load, primarily because of the decay of productively infected cells [4,6,7,8]. The rate of decay becomes slower thereafter because of the release of HIV viruses by macrophages and other long-lived cells of the lymph nodes [4,5,8]. The decline levels off, probably because of reservoirs of long-lived cells still producing HIV virus [4]. In some cases the viral load level may rise again, for example, because of nonadherence to the cART regimen or emergence of resistant virus [4]
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