Long-term Trends in CD4 Cell Counts and Impact of Viral Failure in Individuals Starting Antiretroviral Therapy

UK Collaborative HIV Cohort (CHIC) Study

RA Hughes; JAC Sterne; J Walsh; L Bansi; R Gilson; C Orkin; T Hill; J Ainsworth; J Anderson; M Gompels; D Dunn; MA Johnson; AN Phillips; D Pillay; C Leen; P Easterbrook; B Gazzard; M Fisher; CA Sabin


HIV Medicine. 2011;12(10):583-593. 

In This Article

Abstract and Introduction


Objective The aim of the study was to describe trends in CD4 cell counts in HIV-infected patients after initiation of combination antiretroviral therapy (cART), according to CD4 cell count at initiation (baseline), and to quantify the implications of virological failure for these trends.
Methods Eligible participants from the UK Collaborative HIV Cohort (CHIC) were antiretroviral-naïve and started cART after 1997. Random effects were used to model CD4 cell count trends, accounting for multiple measurements within participants. We assessed whether CD4 cell count trends varied according to baseline CD4 cell count and separately in participants with and without post-cART virological failure. Effects of post-cART virological failure (> 1000 HIV-1 RNA copies/mL) on subsequent CD4 cell counts were evaluated.
Findings A total of 7069 participants were included in the analysis (median follow-up in all baseline CD4 cell count groups was ≥ 35 months). Among participants without virological failure ≥ 6 months after the start of cART, CD4 cell counts continued to increase up to 8 years, with little evidence that differences between baseline CD4 cell count groups diminished over time. Virological failure ≥ 6 months after the start of cART was associated with lower subsequent CD4 cell counts, with greater CD4 cell count reduction for more recent virological failure and higher viral load.
Conclusions Post-cART CD4 cell counts are strongly related to pre-cART CD4 cell counts. CD4 cell count recovery is greatest in individuals who can avoid viral loads > 1000 copies/mL while on cART.


The benefits of combination antiretroviral therapy (cART) are well documented.[1,2] Soon after initiation, most antiretroviral-naïve individuals experience a rapid reduction in HIV viral load accompanied by increases in CD4 cell count and a reduced risk of new AIDS-related events and death. However, there is concern that individuals who do not start cART until their CD4 count has fallen to < 200 cells/μL, either by choice or because they are diagnosed late, may experience poorer immunological responses on cART.[3,4] Individuals starting with CD4 counts < 200 cells/μL are less likely to attain a high (e.g. > 350 cells/μL) CD4 count after starting cART, compared with those starting at higher CD4 counts, despite viral load suppression.[5–7] Other studies have reported that rates of CD4 cell count increase do not differ substantially among those starting cART with different CD4 cell counts,[8,9] suggesting that differences in post-cART CD4 cell count may largely be explained by differences in CD4 cell count at initiation rather than by an inability of the immune system to respond. It is unclear whether most individuals who start with CD4 counts < 200 cells/μL and achieve sustained virological suppression can attain relatively normal CD4 counts if treated for sufficiently long.

In antiretroviral-naïve individuals, virological failure largely occurs following periods of incomplete adherence to treatment, although inadequate drug levels as a result of drug–drug interactions and pre-existing (transmitted) resistance also play a role.[10,11] Incomplete adherence in individuals who are still taking some antiretroviral treatment may lead to emergence of resistant HIV strains that compromise the success of cART. Complete discontinuation of cART ('treatment interruption') is associated with a higher risk of subsequent viral failure, poorer CD4 responses and a higher risk of clinical progression.[12–14] While several studies have assessed the impact of episodes of virological failure on immunological responses [6,8,9,15–18], results are conflicting. No study has, to our knowledge, quantified the effects of low-level compared with higher-level viraemia and the time since virological failure on long-term trends in CD4 cell counts.

The aims of this study were to quantify CD4 cell count trends in a large cohort of antiretroviral-naïve individuals starting cART, to assess whether these trends vary according to pre-cART CD4 cell count, and to estimate the size and duration of the impact of periods of detectable viraemia and treatment discontinuation.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: