Raising the CD4 cell threshold for the initiation of antiretroviral therapy to 500 cells/mm3 would mean that almost 50% of patients would need to start HIV treatment within a year of their infection with HIV, investigators from an international study of seroconverters report in the October 15th edition of Clinical Infectious Diseases.
A threshold of 350 cells/mm3 would result in approximately a third of patients starting therapy within a year of infection with the virus.
Large numbers of patients with HIV are diagnosed late and the investigators comment: “Our findings provide strong support for public health campaigns to encourage early HIV infection diagnosis and testing.”
US HIV treatment guidelines now recommend that patients should start antiretroviral therapy when their CD4 cell count falls below 500 cells/mm3. European guidelines endorse treatment at a CD4 threshold of 350 cells/mm3, as do World Health Organization (WHO) guidelines for middle- and low-income countries.
The earlier initiation of HIV therapy appears to have several advantages. For instance, the results of observational studies suggest that it reduces the risk of both HIV-related and non-HIV-related illnesses. Moreover, prompt therapy may also have public health benefits, significantly reducing the risk of onward HIV transmission.
But raising the CD4 cell threshold for the initiation of therapy will have cost implications for health systems, many of which are already struggling. An accurate understanding of the length of time between infection with HIV and a fall in CD4 cell count low enough to merit therapy is needed to assist planning.
Investigators from the CASCADE (Using Concerted Action on AIDS and Death In Europe) study analysed the medical records of 18,495 individuals with a known date of HIV seroconversion to predict the amount of time between infection with the virus and a fall in CD4 cell count to below 500, 350 and 200 cells/mm3. They also calculated the proportion of patients who would reach these CD4 cell count thresholds one, two and five years after infection with HIV.
Most of the patients (78%) were men and were infected with HIV through sex with another man (55%). Median age at the time of serconversion was 30 years.
The median length of follow-up was 3.74 years.
According to the investigators' calculations, median CD4 cell counts one, two and five years after infection with HIV were 510 cells/mm3, 460 cells/mm3 and 315 cells/mm3, respectively.
If guidelines recommended HIV therapy at a CD4 cell count of 500 cells/mm3, then 48% of individuals would need to start treatment within a year of seroconversion. This compared to 26% of patients if the threshold was 350 cells/mm3 and 9% of individuals if the level was 200 cells/mm3.
The estimated median times between seroconversion and a drop in CD4 cell count to below 500, 350 and 200 cells/mm3 were 1.19, 4.19 and 7.93 years respectively.
However, CD4 cell loss differed according to individual patient characteristics. Older age was associated with a lower CD4 cell count at the time of seroconversion and faster loss of CD4 cells during follow-up (p < 0.001). In addition, individuals infected with HIV via injecting drug use or heterosexual contact had a steeper CD4 cell count decrease than gay men (p < 0.001).
The investigators calculated the time between seroconversion and a fall in CD4 cell count to the study thresholds for three groups of patients.
For heterosexual women aged 25 to 30, the median times between seroconversion and a fall in CD4 cell count below 500, 350 and 200 cells/mm3 were 10.71, 5.66 and 1.63 years respectively.
The times for gay men aged 30 to 35 years were 0.95, 3.94 and 7.67 years, and 0.04, 4.08 and 9.15 years for heterosexual men in the same age group.
“These data signify a substantial increase in the number of individuals who require treatment within the first 5 years after becoming infected following the recent changes in [US and WHO] guidelines,” write the authors. “These estimates…will be essential to health care planners estimating the additional costs of increasing the CD4 cell count threshold for cART (combination antiretroviral therapy] initiation.”
The investigations add: “Our data urgently call for a campaign to encourage early HIV testing to ensure that infected individuals receive a diagnosis of HIV infection and access care well before they reach the CD4 cell count threshold at which treatment is indicated.”
Lodi S et al. Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count threshold <200, <350, and <500 cells/mm3: assessment of need following changes in treatment guidelines. Clin Infect Dis: 53: 817-25, 2011 (click here for the free abstract).