Can HAART prevent SARS?

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HAART should be used to treat and prevent Severe Acute Respiratory Syndrome (SARS) when the next epidemic emerges (a possibility considered likely by many SARS experts) according to an article in the April 1st issue of Clinical Infectious Diseases, which was published online last week.

The article, written by two Chinese HIV researchers on the SARS front-line in Guangzhou (the capital city of Guangdong province) and Beijing, states that HAART may be most effective when used as a preventative tool, which “may be of significant importance in altering the epidemiology of” SARS. Additionally, the authors argue, since SARS is fatal in between 5-10% of cases, HAART may be able to increase the cure rate.

However, the March 26th issue of AIDS includes the first report of an HIV-positive person on HAART to be infected with SARS. Hong Kong doctors report that a 30-year-old Chinese man presented in April 2003 with suspected SARS. He had been HIV-positive for five years, had a CD4 count of 134 cells/mm3, a viral load of 470 copies/ml and was on HAART, including Kaletra, efavirenz, abacavir and tenofovir, plus standard Pneumocystis carinii pneumonia (PCP) prophylaxis. He was also coinfected with hepatitis B virus.

Glossary

Pneumocystis carinii pneumonia (PCP)

Pneumocystis carinii pneumonia is a form of pneumonia that is an AIDS defining illness.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

protease inhibitor (PI)

Family of antiretrovirals which target the protease enzyme. Includes amprenavir, indinavir, lopinavir, ritonavir, saquinavir, nelfinavir, and atazanavir.

protocol

A detailed research plan that describes the aims and objectives of a clinical trial and how it will be conducted.

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

Although the man was treated with the standard anti-SARS protocol(ribavirin 1200 mg and prednisolone 25 mg three times daily) he had a TB flare-up, likely due to the immune-suppressive effects of the prednisolone, and needed additional anti-TB medication 25 days into his infection. Additional 3TC was added to his regimen to prevent flare-up of his hepatitis B infection. However, the man recovered, and 39 days later, he was declared SARS free. No information was provided on his CD4 or viral load counts, however.

The connection between HIV and SARS was first observed during the 2003 outbreak. Despite much contact between the 95 individuals with SARS and 19 HIV-positive individuals on the Guangzhou hospital ward, none of those with HIV became infected with the SARS virus, whereas six of 28 members of the medical staff who worked on the ward did become infected with the SARS virus.

“Most” of the HIV-positive individuals were receiving HAART (although the Chinese doctors do not quantify exactly how many or what anti-HIV medications their patients were taking) and the evidence pointed further towards HAART playing a protective role last September, when a Hong Kong research group reported the results of a study that used Kaletra alongside the standard SARS protocol to treat people with SARS. That study found that when given during the initial symptoms of SARS, Kaletra was associated with a lower overall mortality rate (2.3% vs. 15.6%; P<.05).

The Chinese doctors hypothesised that if Kaletra alone suppressed the SARS virus, then Highly Active Anti-SARS Therapy (HAAST?), combining three or more drugs as in HAART, might be even more effective.

Additionally, since only two of the HIV-infected individuals on the Guangzhou hospital ward were on protease inhibitor (PI)-based HAART, the authors suggest that Kaletra may be substituted for a non-nucleoside when considering the prevention and treatment of SARS, and made the following suggestions:

  • HAART is suggested as SARS prophylaxis for one or two weeks of therapy in those people who have come into close contact with someone with SARS, for example, medical staff.
  • HAART is suggested as SARS therapy for two or three weeks during the acute phase of viral replication.
  • HAART is not recommended for routine use as either prevention or treatment for SARS, but should be prescribed on an individual basis.
  • The authors call for “continued co-operation” between SARS and AIDS clinicians and research scientists, and suggest that a clinical trial comparing PI- and NNRTI-based HAART for SARS should start soon.

Given the report in AIDS, however, it is possible that HAART is not as protective as initially thought, especially since the patient's HAART regimen included Kaletra.

The authors of this report note that “there is also the potential risk of prolonged viral shedding in HIV infection if the clearance of coronavirus [the virus that causes SARS] is ineffective. Furthermore, the mild symptoms of SARS in HIV patients may go unnoticed, making public health control of SARS difficult.”

Finally, it is possible that anti-HIV medications may not be the only antivirals that may (or may not) work against SARS. According to a study in the March issue of Nature by Dutch, Japanese and Chinese scientists the anti-hepatitis C treatment pegylated interferon drastically reduced the amount of SARS virus in six macaques two days prior to infection, compared to the untreated macaques.

Although the interferon wasn’t quite as successful in treating SARS one or three days after exposure, the use of pegylated interferon as a preventative tool “or early post exposure treatment” may reduce the impact on healthcare workers and limit the SARS outbreak, say the researchers.

Further information on this website

Chinese experts ask why AIDS patients resistant to SARS - news story

HIV and SARS: HIV co-discoverer speculates on impact - news story

References

Chen XP et al. Consideration of Highly Active Antiretroviral Therapy in the prevention and treatment of severe acute respiratory syndrome. CID 38, 2004. electronically published 15 March.

Wong, ATY et al. Coronavirus infection in an AIDS patient. AIDS 18 (5); 829-830, 2004.

Haagmans BL et al. Pegylated interferon protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nature 10 (3); 290-293, 2004.