“In a recent series of eight HIV patients treated with infliximab, etanercept, or adalimumab, no deterioration due to HIV disease was observed during a mean observation period of 28 months.”—Ulrich A. Walker, MD
According to Dr. Walker, HIV-associated arthritis is generally self-limited and resolves within 6 weeks, but rheumatic problems likely to occur in patients with HIV include a Reiter's-like spondyloarthropathy, enthesopathy, sacroiliitis, and joint problems that are side effects of ART, as well as gout caused by drug-related hyperuricaemia. Similarities in symptoms between lupus and some HIV also create differential diagnosis problems.Dramatic drop seen in HIV mortality
Bhaskaran et al, from the Medical Research Council Clinical Trials Unit in London, UK, reported that excess mortality among 16,534 HIV-infected individuals with a median follow-up of 6.3 years decreased from 40.8/1000 person-years before the introduction of HAART to 6.1/1000 person-years in 2004-2006 (adjusted excess hazard ratio, 0.05), compared with deaths expected in an equivalent general population cohort.
“By 2004-2006, no excess mortality was observed in the first 5 years following HIV seroconversion among those infected sexually, though a cumulative excess probability of death remained over the longer term (4.8% [95% CI, 2.5%-8.6%] in the first 10 years among those aged 15-24),” Bhaskaran said.
Of the 16,534 patients studied, 2571 died during follow-up compared with 235 deaths expected in an equivalent general population cohort. The numbers of excess deaths decreased from 1275.9 in 31,302 person-years before the introduction of HAART in 1996 to 89.6 excess deaths in 14,703 person-years in 2004-2006.
“Mortality rates for HIV-infected persons have become much closer to general mortality rates since the introduction of HAART. In industrialized countries, persons infected sexually with HIV now appear to experience mortality rates similar to those of the general population in the first 5 years following infection, though a mortality excess remains as duration of HIV infection lengthens,” the authors concluded.
Meanwhile, in the joints...
Ulrich A. Walker, MD, and colleagues from the department of rheumatology at Basel University in Switzerland, offered some hints of what the extended lifespan might mean for rheumatologists. They conducted a comprehensive literature search to analyze the prevalence, presentation, and pathogenesis of rheumatic manifestations in HIV-infected subjects.
“Articular conditions (arthralgia, arthritis, and spondyloarthropathies) are either caused by the HIV infection itself, triggered by adaptive changes in the immune system, or are secondary to microbial infections,” Dr. Walker found. “Muscular symptoms may result from rhabdomyolysis, myositis, or from side-effects of HAART. Osseous complications include osteonecrosis, osteoporosis, and osteomyelitis. Some conditions such as the diffuse infiltrative lymphocytosis syndrome and sarcoidosis affect multiple organ systems.”
Arthralgia has been reported in 5% of patients in retrospective studies and in 45% in prospective studies. The condition most frequently affects the knees, shoulders, and elbows. “An intermittent painful articular syndrome has only a short duration (a few hours), but may require opioid analgesics,” Dr. Walker said. Arthritis has been reported in 10% to 12% of HIV patients and can occur at any point in the course of chronic HIV infection.
“HIV-associated arthritis mainly manifests as a nonerosive oligoarthritis of the lower extremities without enthesopathy, mucocutaneous involvement, and HLA-B27 gene expression.”
However, some of the ARTs used in HAART regimens can raise blood uric acid levels and cause joint pain. HIV-infected patients have hyperuricaemia rates up to 42%.
“In HIV patients, the annual incidence of gout is 0.5%, an order of magnitude higher than the incidence in the normal population,” Dr. Walker said. This can result both from the underlying HIV infection and from drug side effects. Other joint problems that can occur as side effects of ART, particularly protease inhibitors, and include arthralgia, monoarthritis, oligoarthritis, and adhesive capsulitis.
Lupus may improve during the course of untreated HIV infection due to reduction in CD4+ T-cell counts, and flare during immune recovery in response to HAART. “Difficulties in the differential diagnosis between lupus and HIV infection may arise, because there are many clinical and laboratory similarities. For example, oral ulcerations, sicca syndrome, alopecia, arthritis, fever, and neuropathies can be features of both conditions,” Dr. Walker continued.
Translating research into practice
Fortunately, most drugs used to treat patients with rheumatoid diseases can also be used by HIV-infected patients. “When indicated, immunosuppressants and even anti-TNF agents can be used in the carefully monitored HIV patient,” he said. NSAIDs can be used for the relief of musculoskeletal pain the same way in HIV-infected as in non-HIV patients.
“Interestingly, indomethacin has been shown to inhibit HIV replication in vitro, with the dose for 50% inhibition of viral replication corresponding to 50 mg of indomethacin. Indomethacin may therefore be the NSAID to be preferentially considered in HIV patients.”
Other conventional DMARDs also appear to be as safe and effective in HIV-infected patients as in non-HIV patients. TNFα inhibitors also appear to be generally safe and effective and might have beneficial effects on the underlying infection, as exogenous TNFα enhanced HIV replication in cell lines studied in vitro, but this has not been demonstrated clinically.
“In a recent series of eight HIV patients treated with infliximab, etanercept, or adalimumab, no deterioration due to HIV disease was observed during a mean observation period of 28 months,” Dr. Walker concluded.
References
1. Bhaskaran K, Hamouda O, Sannes M, et al. Changes in the risk of death after HIV. JAMA. 2008;300(1):51-59. DOI:10.1001/jama.300.1.51.
2. Walker UA, Tyndall A, Daikeler T. Rheumatic conditions in human immunodeficiency virus infection. Rheumatology. 2008;47:952–959. DOI:10.1093/rheumatology/ken132.
PubMed: Related Articles