CROI: Region of origin and gender significant in long-term changes in CD4 cell count during effective HIV therapy

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Long-term, virologically effective antiretroviral therapy yields smaller increases in the CD4 cell counts of patients originating in sub-Saharan Africa than in patients originating from Western Europe and North America, according to Dutch research presented to the recent 15th Conference on Retroviruses and Opportunistic Infections in Boston.

The research also showed that gains in CD4 cell were lower in men than women and that patients taking anti-HIV treatment that included a boosted protease inhibitor had greater increases in their CD4 cell counts than patients who were taking therapy based on a non-nucleoside reverse transcriptase inhibitor (NNRTI).

The role of ethnicity and gender on long-term changes in CD4 cell count during anti-HIV therapy have not been well studied.


boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

Investigators from the Netherlands’s ATHENA cohort therefore looked at the records of patients starting anti-HIV treatment for the first time between 1996 and 2005. Patients in this cohort are receiving their HIV treatment and care in the Netherlands. They restricted their analysis to individuals whose viral load was suppressed to undetectable levels nine months after starting anti-HIV drugs and who then maintained a viral load below 400 copies/ml. They then looked at increases in the CD4 cell counts of these patients over five years and looked at the effect of region of geographical origin and gender on such changes.

A total of 4,348 patients were included in the study, the majority of whom (80%) were male and from Western Europe and North America (68%). Sub-Saharan Africa was the region of origin for 17% of patients, 4% originated in South-East Asia, and 11% from Latin America and the Caribbean.

When HIV therapy was started, patients from Western Europe and North America had median CD4 cell counts of 210 cells/mm3, significantly higher than patients originating in any other region (sub-Saharan Africa, median 160 cells/mm3; South-East Asia, median 140 cells/mm3; Latin America and the Caribbean, median 170 cells/mm3, p

Five years of antiretroviral therapy yielded a median CD4 cell increase of 360 cells/mm3 in patients from Western Europe and North America. Comparable increases were seen in patients from South-East Asia and Latin America and the Caribbean. In patients from sub-Saharan Africa however, the median five-year increase in CD4 cell count was significantly lower at 320 cells/mm3 (p = 0.004).

Analysis also showed that differences in CD4 cell gains between patients from sub-Saharan Africa and other geographical regions were apparent as early as six months after starting antiretroviral therapy, with African patients gaining a mean of 93 cells/mm3 fewer at this time point than patients from Western Europe and North America (p = 0.008). During the next four and a half years of follow-up, sub-Saharan Africans gained a mean of 11 cells/mm3 fewer per year than patients from other regions (p = 0.008).

Gender also played a role in CD4 cell gain. During the first six months of therapy women gained a mean of 27 cells/mm3 more than men (p = 0.04), and this difference was maintained during subsequent follow-up with women gaining an additional 11 cells/mm3 per year compared to men.

Greater increases in CD4 cell counts were seen in patients who took a ritonavir-boosted protease inhibitor (mean gain, 58 cells/mm3 per year) than in patients who took an NNRTI (mean gain, 36 cells/mm3, p

“In patients achieving and maintaining viral suppression, changes in CD4 cell count during five years of combination antiretroviral therapy were significantly lower in male patients and in patients from sub-Saharan Africa compared with [patients from] western Europe and north America,” conclude the investigators. They add, “this effect was independent of differences in baseline CD4 count and viral load and AIDS diagnosis prior or after starting combination antiretroviral therapy.”


Kesselring A et al. Maximum capacity of restoration of CD4 counts is lower in HIV-1-infected patients from Sub-Saharan Africa during the first months of cART: the Athena cohort. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 817, 2008.