Detectable viral load and low CD4 cell count are risk factors for shingles in HIV-positive people

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A CD4 cell count below 500 cells/mm3 and a detectable viral load are risk factors for herpes zoster (shingles) in HIV-positive people, US investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Complicated herpes zoster was common and was associated with a very low CD4 cell count.

Studies conducted soon after combination antiretroviral therapy became available showed a high incidence of herpes zoster in HIV-positive people. Incidence of the disease was 32 cases per 1000 person-years, far higher than the 3.5 cases per 1000 person-years observed in the general population.

However, there have been considerable improvements in HIV treatment and care over the past decade and investigators at Johns Hopkins University in Baltimore wanted to see if these had had an impact on incidence of herpes zoster. They also wanted to determine if there were any risk factors for the disease.


detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.


Condition caused by a herpes virus infection, involving painful blisters on the skin.



Relating to the eye.

They therefore designed a study involving 4353 people who received care at their centre between 2002 and 2009. Each person who developed herpes zoster was matched with three control individuals who remained disease-free.

During the period of the study, there were 321 cases of herpes zoster involving 262 people. Some 57% of these were incidence (new) cases; the remaining cases involved a recurrence of disease. People with a first case of herpes zoster were significantly less likely than those experiencing a recurrence to be taking HIV therapy (p = 0.004).

The incidence of disease over the entire study period was 9.3 cases per 1000 person-years, significantly lower than the incidence observed between 1997 and 2001, but still higher than that seen in the general population.

Most of the people (62%) with incident herpes zoster were men, African American (75%) and heterosexual (52%). Their median age was 39 years. The majority (63%) smoked, 46% reported drinking alcohol and 27% used illegal drugs.

Median CD4 cell count at the time herpes zoster was diagnosed was 278 cells/mm3, with median viral load being 2581 copies/ml.

Three-quarters of participants were taking antiretroviral therapy at the time of their diagnosis, and 6% had initiated treatment within the past three months.

Herpes zoster was treated with antivirals in 94% of people. The most frequently used therapy was valaciclovir. A fifth of participants required hospitalisation. These individuals had a median CD4 cell count of 233 cells/mm3, 68% were taking anti-HIV drugs and 74% were treated with intravenous aciclovir.

Starting HIV treatment within the previous three months was a risk factor for incident herpes zoster (AOR = 4.02; 95% CI, 1.31-12.41).

“The association between early immune reconstitution after starting ART [antiretroviral therapy] and herpes zoster has been previously observed in smaller studies,” observe the investigators. “Clinicians should be aware of the higher risk of herpes zoster shortly after ART is started.”

A detectable viral load was also a significant risk factor (AOR = 1.49; 95% CI, 1.00-2.24).

Compared to people with a CD4 cell count above 500 cells/mm3, those with a CD4 cell count below 350 cells/mm3 (AOR = 2.46; 95% CI, 1.42-4.23) or between 350 and 500 cells/mm3 (AOR = 2.02; 95% CI, 1.14-3.57) had an increased risk of incident disease.

Over a quarter of participants (28%) developed complications. The most common complications were neuralgia (11%), bacterial infections (6%) and ocular involvement (6%). A CD4 cell count below 50 cells/mm3 was initially identified a risk factor for complications (OR = 2.86; 95% CI, 1.01-8.09). However, this association disappeared when the investigators took viral load into account.

“There are several modifiable risk factors for incident herpes zoster, including having a detectable HIV-1 RNA level [viral load] and a low CD4 cell count,” conclude the authors.

Age was not found to be a risk factor. However, in the general population the risk of shingles increases with age. “As the HIV-infected population continues to age on effective ART, we may see a greater burden of herpes zoster,” the authors therefore suggest.


Blank LJ et al. Herpes zoster among persons living with HIV in the current ART era. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI.0b013e318266cd3c, 2012.