Patients who start antiretroviral therapy with very low CD4 cell counts have a good chance of rapidly achieving and sustaining an undetectable viral load, according to UK data published in the February 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The study also showed that despite having a median CD4 cell count of only 20 cells/mm3 when anti-HIV therapy was started, only 5% of patients died.
HIV treatment guidelines now recommend that antiretroviral therapy should be started when a patient’s CD4 cell count is in the region of 350 cells/mm3. There is good evidence that initiating treatment with a CD4 cell count of this level is associated with good long-term outcomes.
But late diagnosis of HIV is a significant problem in many countries, the UK included. Many patients only have their HIV diagnosed when they have CD4 cell counts below the recommended threshold for initiating treatment. Some individuals are already ill with an AIDS-defining illness when their HIV infection is diagnosed, and in many cases did not consider testing for HIV because they perceived their risk of infection to be low. Other individuals deferred testing because they feared the stigma that surrounds HIV, or arrived in the UK from overseas with profound immune suppression.
In 2001 approximately a fifth of patients who started anti-HIV therapy in the UK did so with a CD4 cell count below 50 cells/mm3, and most of these patients had had their HIV diagnosed late. Although access to HIV therapy is expanding around the world, between 25% - 55% of patients who start treatment in resource-limited settings do so with very severe immune suppression and a CD4 cell count below 50 cells/mm3.
Even though late initiation of antiretroviral therapy is a significant issue in many countries, few studies have evaluated the outcome of patients who start treatment with a CD4 cell count below 50 cells/mm3.
Therefore, investigators from the UK Collaborative HIV Cohort (UK CHIC) assessed the virological outcome in patients starting anti-HIV therapy with a very low CD4 cell count since 1996. They also calculated survival in these severely immuno-suppressed patients.
A total of 1117 patients from ten large HIV treatment centres in south east England and Edinburgh who started treatment with a low CD4 cell count between 1997 and 2005 were included in the study. All had a CD4 cell count below 50 cells/mm3 and a viral load above 1000 copies/ml when they commenced antiretroviral therapy.
The patients were divided into four groups according to the year in which they started antiretroviral therapy: 1997 - 98; 1999 – 2000; 2001 – 2002; 2003 – 2005.
Median CD4 cell count was just 20 cells/mm3 when the patients started treatment. Their median age was 37 years, 74% were men, and approximately 50% acquired HIV infection during heterosexual sex.
Antiretroviral therapy based upon a non-nucleoside reverse transcriptase inhibitor (NNRTI) was initiated by 58% of patients, with 36% starting treatment with a protease inhibitor-containing regimen, 4% triple nucleoside analogue treatment (which would now be considered suboptimal) and 2% with treatment from all three main classes of antiretrovirals. In the period since 1999, the proportion of patients starting NNRTI-based treatment has been steady at approximately 68%, with 25% starting protease inhibitor-based treatment in this time period.
Twelve weeks after starting anti-HIV treatment 80% of patients had a viral load below 400 copies/ml. At week 48, 83% of patients had a viral load below this level.
Since 1999 viral load tests have been in routine use in the UK with a lower limit of detection of 50 copies/ml. The proportion of patients since 1999 with a viral load below 50 copies/ml twelve weeks after starting treatment has averaged 49%, with 77% having a viral load below 50 copies/ml at week 48.
There have been significant improvements in anti-HIV therapy since 1996, with drugs that are easier to take, more potent and less toxic becoming available. There have also been improvements in HIV care. The investigators wanted to see if these improvements were associated with an increase in the proportion of patients achieving virological suppression over the course of the study. They found that the chances of achieving virological suppression increased year on year until 1999 and remained more or less stable thereafter before falling slightly between 2003- 2005.
They then looked to see if any particular patient characteristics were associated with an increased chance of HIV suppression. They found that women were more likely to have a viral load below 400 copies at week 48 than men (odds ratio [OR], 1.74; 95% CI, 1.07 – 3.02). Older patients were also more likely to achieve effective suppression of HIV (OR, 1.46; 95% CI, 1.11 – 1.96 for every ten years).
There was a trend for gay men to have a better response to treatment than individuals from other risk groups (p = 0.06). Patients of black ethnicity appeared less likely to have a good virological response to treatment than white patients, but the difference was not statistically significant (OR, 0.65; 95% CI, 0.37 – 1.42).
In the 2003 – 2005 calendar period the investigators estimated the probabilities of a women aged 25, 35 and 45 who started treatment with a CD4 cell count below 50 cells/mm3 achieving a viral load below 50 copies/ml at week 48 to be 71%, 75% and 79% respectively. For men the probabilities for these ages were 68%, 73% and 78%.
Of the patients who started anti-HIV treatment after 1999, 134 (15%) progressed to AIDS and 48 (5%) died. The investigators estimated that the probability of being alive twelve months after starting treatment was 98% for those who did so between 1999 – 2000, 97% for those starting treatment between 2001 – 2002, and 98% for those who initiated therapy between 2003 – 2005. The corresponding AIDS-free survival probabilities for each of these periods were 81%, 83% and 84%.
“It is encouraging to note that viral suppression can be achieved fairly rapidly in persons initiating therapy at a severely advanced state of immune deficiency”, conclude the investigators, adding “these data, albeit under conditions of good infrastructure for care delivery, are a useful comparator for other populations starting therapy at similar levels of immunodeficiency. Such information may be valuable for evaluating the success of antiretroviral therapy in rollout programmes.”
Porter K et al. Changes in outcome of persons initiating highly active antiretroviral therapy at a CD4 cell count less than 50 cells/mm3. J Acquir Immune Defic Syndr 47: 202 – 205, 2008.