Lyme neuroborreliosis (LNB) is the most common bacterial central nervous system (CNS) infection in the temperate parts of the northern hemisphere. European LNB most often presents as a painful meningoradiculoneuritis, with or without facial palsy or other cranial neuritis (Garin-Bujadoux-Bannwarth syndrome). More uncommon symptoms include deficits of other cranial nerves, myelitis and encephalitis [
To date, only five single cases of co-infection with human immunodeficiency virus (HIV) -1 and LNB have been published [
], all of whom were treated with intravenous third-generation cephalosporins. In Sweden, the recommended treatment for LNB has long been oral doxycycline. We now present a case series of four patients with HIV-1 infection that have been diagnosed with LNB and successfully treated with oral doxycycline.
Only a few reports of HIV-1 and LNB co-infection have been presented. Previously, this was considered to be due to the non-overlapping epidemiology of the two diseases; with LNB mainly being a rural disease, while HIV-1 is more common in urban settings [
]. HIV-1 patients today who are treated with ART have a life expectancy approaching that of the general population and they seldom have opportunistic infections [
], thereby enabling them to lead active lives with outdoor activities that increase the risk of contracting
infection. The incidence of LNB is highest in Central Europe [
], where the prevalence of HIV-1 infection is also substantially higher than in Sweden, where these four patients were diagnosed. It can therefore be expected that HIV-1 and LNB co-infection is more common than has previously been described.
The diagnosis of LNB rests on a combination of clinical symptoms, CSF analyses and serology. The results are sometimes contradictory or difficult to interpret, making the diagnosis uncertain. In these four patients, however, the diagnosis of LNB is considered definite. At the time of diagnosis, all these patients had CSF mononuclear pleocytosis, with cell counts higher than the levels normally observed in HIV patients [
]. Patients 1, 2 and 3 all had high titers of IgG antibodies to
in their CSF and serum and a positive
antibody index, indicating the intrathecal production of specific
antibodies. Patient 4 seroconverted from negative to positive IgG antibodies to
in his serum and CSF. Furthermore, all the patients displayed a rapid response to anti-
treatment. There is a well-known cross-reactivity between the
and HIV patients are over-represented among patients with syphilis. However, screening tests for syphilis were negative in all four patients. Other bacterial, viral and fungal CNS infections were also ruled out.
Four of the five previously published cases of HIV-1 and LNB co-infection presented with typical symptoms of LNB, including bilateral facial palsy [
], headache [
], meningoradiculitis [
], and facial palsy and meningoradiculitis [
]. These four patients showed complete recovery on treatment with intravenous third-generation cephalosporins. The fifth patient presented with more severe symptoms consistent with encephalomyelitis: altered gait and difficulties in using her hands. Treatment with intravenous third-generation cephalosporins resulted in only partial recovery [
Three of the four patients described in this article presented with more severe, atypical symptoms and pathology than are usually seen in patients with LNB, including one with cognitive impairment, one with a pontine infarction and one with normal-pressure hydrocephalus. However, concomitant medical disorders such as alcohol abuse in Patient 1 and previous Guillain-Barré in Patient 2 might have influenced the clinical course of LNB. The atypical clinical picture might also have been caused by the long disease duration before
diagnosis and subsequent treatment; a couple of months for Patient 2, and more than a year for Patient 3. An explanation for the delayed diagnosis could be that more common HIV-associated opportunistic infections and other diseases were initially suspected. Apart from the concomitant medical disorders and the long disease duration, it must, however, also be suspected that these patients' impaired immunity contributed to the severity of the disease, as none of these three patients had normal levels of CD4 cells. The exact mechanisms by which impaired immunity in HIV infection might influence the course of disease in LNB remain to be clarified. Acute cerebral infarction is a known but very rare manifestation of LNB, with the pathological mechanism suspected to be a selective inflammatory process of small cerebral arteries. Patient 2 matches those previously described with the involvement of the posterior circulation and a generally favorable outcome after treatment [
]. Normal-pressure hydrocephalus in patients with LNB is an even rarer manifestation, with only a few known cases. The pathological background is not understood. As with Patient 3, previously described cases have also shown complete improvement after antibiotic treatment, with no need for ventricular shunting therapy [
The European Federation of Neurological Societies has published guidelines on the management of LNB [
]. According to these guidelines, patients with early LNB with CNS symptoms or patients with late (more than six months of symptoms) LNB should be treated with intravenous ceftriaxone. Of the four patients presented here, three had late LNB with CNS symptoms and were also the most immunocompromised. The good outcome of treatment with oral doxycycline in these patients, in combination with the CSF follow-up analyses, suggests that oral doxycycline is an excellent alternative to intravenous ceftriaxone in this patient group.
One interesting observation in Patients 1, 2 and 3 was the relatively higher HIV viral load in CSF compared with plasma at time of diagnosis of the
). This shows that concomitant meningeal inflammation and the recruitment of lymphocytes to the CNS in HIV infection increase the CNS viral load, probably by the Trojan horse pathway [
]. Similar findings have been observed in patients with cryptococcal and tuberculous meningitis [
The authors declare that they have no competing interests.
All the authors contributed to the design and data analysis of the study, the writing of the article and approved the final version.