Virulence of HIV has increased since first reports of AIDS

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HIV may have evolved to become more virulent over the course of the epidemic, according to the results of a meta-analysis published in the online edition of AIDS.

The study estimates that six months after infection, the CD4 cell count of a person infected with HIV in 2010 was likely to stabliise at a level approximately 150 cells below that of a  person infected in the early 1980s. This implies that HIV transmitted in recent years is likely to lead to more rapid development of illness compared with HIV transmitted 30 years ago.

US investigators analysed the results of studies conducted between 1984 and 2010 to see if two key prognostic markers - CD4 cell set point and viral load set-points (the level of CD4 cells and viral load immediately after primary infection) - had changed. All the studies involved patients from North America and Europe and most individuals were therefore infected with HIV-1 subtype B.

Glossary

virulence

The power of bacteria or viruses to cause a disease. Different strains of the same micro-organism can vary in virulence.

 

meta-analysis

When the statistical data from all studies which relate to a particular research question and conform to a pre-determined selection criteria are pooled and analysed together.

set point

The viral load that the body settles at within a few weeks to months after infection with HIV. Immediately after infection, a person’s viral load is typically very high. After a few weeks to months, this rapid replication of HIV declines and the person's viral load drops to its set point. A higher viral set point suggests that, in the absence of treatment, disease will progress faster than in a person with a lower set point. 

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

Increasing virulence of the virus was suggested by an annual fall in CD4 cell count of approximately 5 cells/mm3 and an increase in viral load set point of 0.013 log10 copies/ml.

“Over the course of the HIV-1 subtype B epidemic in North America and Europe there are overall trends of decreasing baseline CD4 cell counts and increasing set point viral loads,” comment the investigators.

They calculated that these changes represent “a loss of 148 CD4 cells/mm3 and an increase of 0.39 log10 copies/ml RNA over a 30 year period (from the first CDC report of the epidemic in 1981).” Even larger changes were observed in patients with a known date of infection with HIV.

However, there was evidence that the virulence of the virus had slowed in recent years.

Earlier research examining the virulence of HIV has produced conflicting results. Nevertheless, it is important to establish an accurate understanding of this issue as it has implications for both treatment and prevention strategies. If the virus has become more virulent, this could suggest that it is easier to transmit. Similarly, a more virulent virus would hasten the need for antiretroviral therapy.

Investigators therefore conduced a meta-analysis of studies examining trends in baseline CD4 cell counts and viral load set points.

A total of twelve studies monitoring CD4 cell counts were identified. They included approximately 21,000 individuals, and nine studies enrolled patients with an established date of HIV seroconversion.

Viral load set-point was assessed in eight studies involving approximately 11,000 patients. In six of these studies, the population comprised individuals with a documented date of seroconversion.

The studies were published between 1996 and 2009 and provided data on newly diagnosed patients over a mean of 17 years. All were conducted in Europe and North America and therefore the majority of patients were infected with subtype-B virus.

The meta-analysis showed a statistically significant decreasing trend in CD4 cell count of – 4.93 cells/mm3 each year. When analysis was restricted to seroconvertors, the mean annual loss in CD4 cell count increased to – 6.01 cells/mm3.

Viral load set-point increased by a mean of 0.013 log10 copies/ml. Restricting analysis to seroconvertors showed an even larger mean increase (0.018 log10 copies/ml).

“These trends are consistent with increased virulence of HIV-1 due to viral evolution in the human population,” suggest the investigators.

Overall, they estimate that baseline CD4 cell count has fallen by a mean 148 cells/mm3 and viral load set-point has increased by a mean of 0.39 log10 copies/ml since the first reports of AIDS in the early 1980s.

Restricting analysis to seroconvertors showed even larger changes with a mean reduction in baseline CD4 cell count of 180 cells/mm3 with a corresponding mean increase in viral load set-point of 0.54 log10 copies/ml.

They believe that their findings have both clinical significance and implications for HIV prevention.

“A 0.3 log10 copies/ml change is a clinically significant change in viral load,” write the authors. “The relationship between set point and viral load disease progression predicts that an increase in set point of 0.5 log10 copies/ml decreases the median time to AIDS by three years…and will modify the per year transmission rate by 37%.”

However, the magnitude of changes in CD4 cell count and viral load set-point lessened over time. 

“Overall, our meta-analysis of trends in prognostic markers of HIV-1 disease progression suggests that HIV-1 has become more virulent over the 30-plus year history of the global HIV/AIDS epidemic,” conclude the investigators. They call for studies in other populations and locations affected by the epidemic, especially sub-Saharan Africa “to assess our findings and its future impact.”

References

Herbeck JT et al. Is the virulence of HIV changing. A meta-analysis of trends in prognostic markers of HIV disease progression and transmission. AIDS 25, online edition, doi: 10.1097/QAD.0b013e32834db418, 2011 (click here for the free abstract).