Both HIV-positive individuals and their clinicians require further education around the benefits of earlier initiation of therapy, and better understanding of the risks of treatment interruption, according to a Health Protection Agency (HPA) study presented to the 14^th Annual British HIV Association (BHIVA) Conference last month in Belfast.

The study’s authors, examining the reasons why a significant minority of previously diagnosed individuals under care have CD4 counts below 200 cells/mm³, also recommend adherence support and recall of poor attendees in order to reduce the number of individuals with low CD4 counts.

Two years ago, HPA investigators presented data to the Twelfth BHIVA Conference in Brighton which found that one in five individuals with CD4 counts below 200 cells/mm³ receiving care in the UK in 2004 were not on antiretroviral therapy (ART).

Of particular concern was that 70% of these were not due to late diagnosis, and that some patients appeared to have had low CD4 cell counts for several years and should have already have been on ART.

At this year’s BHIVA Conference, the HPA attempted to explain the reasons why a significant minority of diagnosed individuals had CD4 counts below 200 cells/mm³ by reviewing the case notes of more than 400 HIV-positive individuals with low CD4 counts receiving care at two larger inner London HIV treatment centres. They also wanted to see what action was taken in order to improve the patients’ immune status.

A total of 3881 patients at the Mortimer Market Centre and Guy’s & St Thomas’ Hospitals had a CD4 count performed between 1^st January 2007 and 30^th June 2007 and the investigators found that 12% (467/3881) had a CD4 count below 200 cells/mm³. Data were available on 423/467(91%).

These 423 individuals were categorised into three groups for further analysis:

• Group A (late/never starters): Patients previously known to have had a CD4 cell count above 200 cells/mm³

• Group B (slow/discordant responders): Patients diagnosed before the study period who had never achieved a CD4 cell count above 200 cells/mm³

• Group C (late diagnosis): Patients first diagnosed within the study period with a CD4 cell count below 200 cells/mm³

The investigators found that there were significant differences in the demographics of patients with low CD4 counts.

Compared with individuals of white ethnicity, individuals of black ethnicity were significantly more likely to be slow/discordant responders (36% vs. 57%) or to be diagnosed late (34% vs. 61%: p=0.003). The same was true for men and women who had acquired HIV through heterosexual sex compared with men who had sex between men (p<0.001).

Group A (late/never starters)
A total of 251 (60%) individuals had previously had a CD4 count above 200 cells/mm³. Just under half (121) of the 251 (48%) had been offered ART before their CD4 count had dropped below 200 cells/mm³. However, 174 (69%) were not taking antiretroviral therapy at the time of their CD4 drop to below 200 cells/mm³.

Of the 170 individuals with recorded data this was due to the following reasons:

• Unstructured treatment interruption, 51 (30%)

• Patient decline, 33 (19%)

• Patient attending infrequently for HIV care, 30 (18%)

• Transient CD4 drop i.e. “blip”, 7 (4%)

• No indication for ART at previous clinic attendance (median CD4 count 260 cells/mm³ at a median of nine weeks prior to their first CD4 count below 200), 36 (21%)

• Other, 13 (8%)

Of the 174 individuals not taking antiretroviral therapy at the time of their CD4 drop below 200 cells/mm³, 133 (76%) started antiretroviral therapy a median of seven weeks after their first documented CD4 count below 200 cells/mm³.

The investigators also found that a significant minority of patients, (77; 31%), were taking ART at the time of their CD4 decline to below 200 cells/mm³.

Of the 76 individuals with recorded data, this was due to the following reasons:

• Discordant treatment response, 7 (9%)

• HIV treatment failure due to non-adherence, 21 (28%)

• HIV treatment failure due to resistance, 9 (12%)

• Transient CD4 drop i.e “blip”, 31 (41%)

• Other 8 (11%)

Group B (slow/discordant responders)
A total of 128 (30%) individuals with a CD4 count below 200 cells/mm³ had never achieved a CD4 count above this threshold.

The majority, (115; 90%) were taking ART at the end of the study period without achieving CD4 recovery, and the remaining (13; 10%) had been offered treatment. Of these six (46%) did not start ART (four declined and two did not attend again during the six month study period) and seven (54%) had interrupted treatment.

Of the 90% on ART, the median time of follow-up prior to the study period was 16 months and by the end of the study period, the median time on ART was 59 weeks.

It appears that most of these individuals were diagnosed late, with a median CD4 count at ART initiation of 50 cells/mm³ (interquartile range: 20-90). In addition, 79 of the 115 individuals on ART (69%) had a HIV viral load below 50 copies/ml at the end of the study period.

Group C (late diagnosis)
A total of 44 (10%) individuals with a CD4 count below 200 cells/mm³ were diagnosed during the study period. Their median CD4 count at diagnosis was 60 cells/mm³ (IQR: 30-140) and 39% had an AIDS-defining illness.

All 44 individuals were offered treatment at a median of four weeks (IQR 2-6) of which 98% (n=43) subsequently initiated ART.

Discussion
In this study the majority of individuals (60%) with a CD4 count below 200 cells/mm³ had been diagnosed and in care prior to their reaching the lower threshold for commencing ART. The remaining 40% appear to have been diagnosed late.

The investigators suggest that “strategies aimed at patient and doctor education around earlier therapy initiation and avoidance of treatment interruption, adherence support and recall of poor attendees may reduce prevalence of low CD4 counts.”

Although they recommend that, “setting standards for HIV units to reduce numbers of patients at high risk of opportunistic infection is greatly welcomed,” they note that “a significant number of patients in this group have achieved good virological control but have delayed immune reconstitution.”

They also note that reduced frequency of CD4 count measurements in patients with good immunological and virological responses to therapy – already in place at the Mortimer Market Centre – “may result in centres reporting a spuriously higher proportion of patients with a CD4 <200. This will impact on interpretation of the proposed standards.”

The conclude by hoping that their data “will help inform those responsible for designing strategies which aim to reduce the number of individuals in care who remain vulnerable to opportunistic disease and hospitalisation.”

Reference
Dosekun O et al. Are there opportunities to reduce the number of patients with a CD4 count less than 200 attending for routine HIV care? Fourteenth BHIVA Conference, Belfast. Abstract P147, 2008.

aidsmap resources

latest news

• BHIVA: Starting ART earlier has cost implications, public health benefits, says HPA
• BHIVA: HIV-positive women at increased risk of late pregnancy loss
• Combining rifampicin with increased doses of lopinavir/ritonavir tablets leads to dangerous increases in liver enzymes
• Death rate in Malawi falls by up to 35% due to free HIV treatment
• Circumcision and partner reduction should be priorities for HIV prevention, say US researchers
• HIV, but not HHV-8, found to increase risk of pulmonary arterial hypertension
• HIV reduces body's ability to control hepatitis C replication
• Does tenofovir increase the risk of efavirenz-associated liver side-effects?
• Nearly all patients with NNRTI resistance could benefit from etravirine, UK analysis shows
• BHIVA: Many patients and clinicians still need educating about the benefits of treatment