A low baseline CD4 cell count does not mean that HIV-positive Ethiopians have poorer survival, according to a study published in the September 1st edition of the Journal of Infectious Diseases. The investigators found that median survival time for Ethiopians was comparable to that of Dutch gay men and injecting drug users before effective anti-HIV treatment became available, because the Ethiopians lost CD4 cells at a slower rate than the Dutch.
Several earlier studies have indicated that HIV-negative Ethiopians have lower CD4 cell counts than other Africans or individuals from industrialised countries. CD4 cell counts in HIV-negative Ethiopians ranges between 590 – 775 cells/mm3 compared to 800 – 1250 cells/mm3 amongst uninfected populations elsewhere in Africa and 1050 cells/mm3 amongst HIV-negative Dutch gay men. It has also been shown that the degree of immune activation is higher in Ethiopians than Europeans even before HIV infection.
Because of these differences investigators hypothesised that HIV-positive Ethiopians would experience a faster rate of disease progression than HIV-positive Dutch individuals.
To test this hypothesis investigators compared the rate of CD4 cell count decline between 149 HIV-positive Ethiopian factory workers recruited between 1997 and 2001 and 306 HIV-positive Dutch gay men and 181 HIV-positive Dutch injecting drug users followed between 1990 – 1995, before effective anti-HIV therapy became available.
Survival time was estimated using a model comparing loss of CD4 cells between the Ethiopian and Dutch study populations.
On entry to the study, the median age of the three arms was similar (34 years for the Ethiopians, 35 years for the Dutch gay men and 32 years for the Dutch drug users). Baseline median CD4 cell count was lower in the Ethiopians (333 cells/mm3) than the drug users (480 cells/mm3), but similar to that seen in the Dutch gay men (370 cells/mm3). CD4 cell percentage was also lower in the Ethiopians (20%) than either of the Dutch populations (drug users, 32%; gay men, 28%). In addition, the CD4:CD8 cell ratio was lower amongst the Ethiopians at 30% than the Dutch injecting drug users (63%) and Dutch gay men (50%).
Median viral load, however, was lower amongst the Ethiopians (10,000 copies/ml) than the Dutch gay men (25,000 copies/ml) or drug users (36,000 copies/ml).
A total of 35 deaths were recorded. Median CD4 cell count before death was 20 cells/mm3 for gay men, 180 cells/mm3 for drug users and 119 cells/mm3 for the Ethiopians.
Estimates for survival amongst the Ethiopians varied between nine and 13 years. The investigators note how similar these estimates were to those for individuals in industrialised countries prior to the availability of effective anti-HIV treatment.
The investigators noted that the rate of CD4 cell loss was dependent on baseline CD4 cell count and that the higher the baseline CD4 cell count, the more rapid the loss of cells. This was true for both the Dutch populations and the Ethiopian individuals. They comment, “since Ethiopians had lower baseline CD4 T cell counts, they thus lost their cells more slowly than did Dutch HIV-infected individuals.”
CD4 cell loss was then compared by the investigators between Dutch and Ethiopian individuals with comparable baseline counts. They write, “at a CD4 cell count of 333 cells/mm3…the annual loss for Ethiopians was 32 cells/mm3 whereas it was 68 cells/mm3 and 79 cells/mm3 for Dutch homosexual men and drug users, respectively.”
Overall, the rate of CD4 cell decline was significantly lower amongst Ethiopians than either of the Dutch populations (p < 0.01).
Neither viral load, nor infection with the SI/X4 HIV-strain (present in 32% of gay men and 14% of drug users) could explain the faster loss of CD4 cells seen in the Dutch populations.
The investigators call their findings “remarkable” and comment, “Ethiopians turned out to lose their CD4 cells at least twice as slowly as Dutch individuals, even when Dutch and Ethiopian individuals with similar CD4 cell counts were compared.”
A possible explanation for the slower rate of CD4 cell loss is offered by the investigators: “Compared with people in the Western world, Ethiopians and people living with the developing world generally, have been strongly selected for their ability to survive despite chronic immune activation because of the high burden of infectious diseases”. Consequently, individuals in developing countries developed a more efficient immune response involving a low immune-activation phenotype over many centuries. The investigators note “it is exactly this phenotype that has been shown to be associated with slow progression of HIV in cohorts in the Western world.”
Mekonnen Y et al. Low CD4 T cell counts before HIV-1 seroconversion do not affect disease progression in Ethiopian factory workers. J Infect Dis: 192 (739 - 748), 2005.