Can some co-infections slow down HIV disease progression?

A review article published in the 15^th September edition of The Journal of Infectious Diseases has outlined the possible protective effects of a range of co-infections on HIV disease progression.

The article’s authors, from Thomas Jefferson University in Philadelphia, cite evidence for the possible attenuation of HIV infection by GB virus C, as well as the measles virus, scrub typhus, human T lymphotropic virus types 1 and 2 (HTLV-1 and –2), HIV-2 and tuberculosis. They also call for further research into the effects of these co-infections on HIV disease.

Although co-infection disease-causing organisms and vaccinations usually increase HIV replication, more data are emerging, suggesting that a limited number of co-infections may have the opposite effect of slowing down HIV disease. These, the writers explain, have various modes of action in attenuating the HIV progression, which may help experts to understand how HIV disease progresses more fully.

“The mechanisms of HIV-1 attenuation in dual infection are complex and multilayered and are likely to include direct molecular and cellular suppression of HIV-1 replication, innate immune processes, and effects on clinical disease progression,” they write. “Further research is required to elucidate the underlying mechanisms of various co-infections and HIV-1 suppression.

“These future studies may potentially lead to novel therapeutic approaches to combat HIV-1 disease,” they conclude.

GB virus C

One co-infection that has received substantial attention in the medical literature is GB virus C. Although a close relative of hepatitis C, it does not cause disease in humans. It is sometimes referred to as hepatitis G virus.

A number of observational studies have found that HIV-positive patients co-infected with this virus are less likely to die of HIV disease, have lower HIV viral loads and have higher CD4 cell counts than those without co-infection. These effects have been attributed to decreased expression of the CCR5 co-receptor that most forms of HIV use to enter their target cells. However, other explanations include alterations in the levels of cytokines, chemicals released by immune cells to co-ordinate the immune response.

These studies have led some experts to advocate deliberate infection of HIV-positive patients with this virus, in order to slow down the progression of HIV disease.

However, the review’s authors highlight two recent studies that have cast doubt on a causal link between GB virus C infection and an attenuation of HIV disease. In contrast to previous findings, these studies failed to show significant effects on death rates, AIDS or progression of HIV disease, although one showed that clearance of the virus led to disease progression.

“One hypothesis suggests that GB virus C persistence depends on CD4 T-cells that are susceptible to infection”, the authors explain. “The CD4 T-cell count decrease associated with HIV-1 disease progression may be a cause, rather than a result of GB virus C RNA loss.”

Other co-infections

The authors also summarise findings relating to other co-infections, including the measles virus, which is common in central and eastern Africa. Although it is highly immunosuppressive, a study of Zambian children showed that measles-infected children have lower HIV viral loads in the early stages of measles infection compared to measles-free children. This may occur through a decrease in the number of CD4 T-cells available for infection with HIV or through alterations in chemokine and cytokine levels.

Similarly, the bacterial disease scrub typhus may reduce HIV replication, particularly of HIV strains that use the CXCR4 receptor to enter CD4 T-cells. These strains of HIV are more common in the later stages of HIV infection and are linked to rapid disease progression. Scrub typhus is an infectious disease caused by Orientia tsutsugamushi, and is commonly found in south-east Asia and the south-western Pacific.

The authors also describe the results of studies analysing patients co-infected with viruses that are similar to HIV-1. These viruses, such as HTLV-1 and –2, and HIV-2, may be linked to slower declines in CD4 cell count, although they stress that further studies are needed.

More controversially, the doctors discuss some recent test-tube evidence linking co-infection with Mycobacterium tuberculosis, the bacterium responsible for tuberculosis (TB), to reduced HIV replication. Although this seems to contradict evidence from HIV-positive patients who also have TB, they point out that this “suggests a more complex interaction between the two organisms, and further studies are required to elucidate the inhibitory effects of M. tuberculosis on HIV-1 replication.”

The authors also mention evidence for a protective effect of influenza A virus, human herpesvirus (HHV)-6 and –7 and bacteria such as lactobacillus.