HIV-positive patients who maintain a CD4 cell count above 500 cells/mm3 for at least eight years after their HIV diagnosis have very low levels of HIV DNA soon after their infection with HIV and subsequently have very slow increases in this marker, French investigators report in the January 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators therefore believe that “early prognostic factors” are associated with long-term non-progression of HIV.
Long-term non-progressors are defined as HIV-positive individuals who do not need to take HIV treatment and who remain symptom-free with a CD4 cell count above 500 cells/mm3 for at least eight years after their infection with HIV.
Most of the research involving this small group of patients (who only represent between 1% and 5% of HIV-positive individuals), has focused on their outcomes once their non-progressor status has been identified. Little is therefore known about the earlier years of HIV infection in these patients.
Investigators from France described the course of HIV infection in a group of 664 patients in the ANRS SEROCO/HEMOCO cohorts who had a CD4 cell count above 500 cells/mm3 at the time of their HIV diagnosis, which was between 1988 and 2006.
The investigators found that 60 of these patients were still symptom-free and had a CD4 cell count above 500 cells/mm3 without antiretroviral therapy eight years after their diagnosis. These patients were therefore long-term non-progessors.
Researchers looked at the factors associated with long-term non-progressor status; the natural history of HIV infection in non-progressors; and the factors associated with the loss of non-progressor status either because of a fall in CD4 cell count to below 500 cells/mm3 or the appearance of symptoms of HIV infection.
Non-progressors were younger than patients whose HIV disease progressed at the time of HIV diagnosis (25 vs 28, p = 0.02). They also had higher median CD4 cell counts at diagnosis (840 vs 668 cells/mm3, p < 0.0001) and higher median CD4 cell percentages (p = 0.0002).
Baseline viral load was lower in non-progressors than progressors, and a higher proportion of non-progressors had an undetectable viral load at the time of HIV diagnosis (24% vs 3%).
Further, non-progressors also had lower amounts of HIV DNA in peripheral blood mononuclear cells than progressors and were more likely to have a baseline HIV DNA below the limit of detection (13% vs 1%).
Next, the investigators looked at the natural history of HIV infection in the patients with long-term non-progressor status.
They found that median CD4 cell count fell by between 32 and 16 cells/mm3 per year depending on age (bigger falls were seen in younger patients).
Among all the 59 long-term non-progressors with viral load information available, mean viral load at the time of HIV diagnosis was a little over 1500 copies/ml. It increased by a mean of 0.040 log10 copies per year, and the mean eight year total increase in viral load was 0.32 log10, meaning that mean viral load at this point was approximately 3000 copies/ml.
Viral load was undetectable at baseline in 16 non-progressors. It remained undetectable for a median of six years in these patients and seven individuals maintained an undetectable viral load for ten years.
There was information on baseline HIV DNA for 47 patients. At baseline the mean was 2.19 log copies/106 in men and 1.75 log copies/106 in women. It increased by mean of 0.069 log copies/106 per year, the total mean eight year increase being 0.55 log copies/106.
In 19 patients, the first HIV DNA measurement was undetectable. Of these individuals, ten also had an undetectable baseline viral load. HIV DNA remained undetectable for a median of 3.6 years in these 19 patients.
Median duration of follow-up for the 60 long-term non-progressors was 16 years. During this period, 36 patients lost their non-progressor status. This occurred a median of eleven years after diagnosis with HIV (or three years after achieving non-progressor status). All but three of these 36 patients lost their non-progressor status because their CD4 cell count fell below 500 cells/mm3.
The only baseline factor associated with loss of non-progressor status was HIV DNA level. Patients with HIV DNA above the limit of detection at the time of their HIV diagnosis were almost three times more likely to experience HIV disease progression than patients with an undetectable HIV DNA at baseline (adjusted hazard ratio, 2.8, 95% CI ,1.2-6.8).
Furthermore, the investigators found that patients who lost their non-progressor status had higher annual increases in HIV DNA (above 0.103 log copies/106, adjusted hazard ratio, 2.2, 95% CI, 1.0-4.8).
“One of the main interests of this study lies in its ability to identify early prognostic factors of becoming a long-term non-progressor”, comment the investigators, “our results show that patients with baseline HIV [viral load] and HIV DNA below detection limits have a 60% chance of being long-term non-progressors”.
They conclude, “our study shows that long-term non-progressor status may be established early during infection. Low level of HIV in peripheral blood mononuclear cells at enrolment was found to be a strong predictor of the duration of long-term non-progression.”