Management of Buruli ulcer–HIV coinfection. Technical update

Übersicht

Areas of Africa endemic for Buruli ulcer (BU), caused by Mycobacterium ulcerans, also have a high prevalence of human immunodeficiency virus (HIV), with adult prevalence rates between 1% and 5%. However, there is limited information on the prevalence of BU–HIV coinfection. Preliminary evidence suggests that HIV infection may increase the risk of BU disease. In the Médecins Sans Frontières project in Akonolinga, Cameroon, HIV prevalence was approximately 3–6 times higher among BU patients than the regional estimated HIV prevalence. Similarly in Benin and Ghana, BU patients were 8 times and 3 times respectively more likely to have HIV infection than those without BU. Further study is needed to clarify this association and enhance knowledge about the prevalence of BU–HIV coinfection in endemic areas.

HIV may affect the clinical presentation and severity of BU disease, with a reported increased incidence of multiple, larger and ulcerated BU lesions in HIV-infected individuals. Additionally in the Akonolinga project, the main lesion size was significantly increased with decreasing CD4 cell-count levels.

There may be significant interactions between BU antibiotics and some antiretrovirals. For instance, dolutegravir (DTG) needs to be doubled-dosed when co-administered with rifampicin, while boosted protease inhibitors are generally not recommended for use in patients taking rifampicin because of significant reduction of their levels. Efavirenz is recommended over nevirapine in non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens given the reduction in nevirapine levels when combined with rifampicin. However, efavirenz can reduce clarithromycin levels by up to 39% , which likely further compounds the known significant reduction of clarithromycin levels by rifampicin. Although the clinical consequence of this drug–drug interaction is unknown, it could lead to reduced effectiveness of the rifampicin and clarithromycin regimen for BU treatment, with secondary treatment failure and drug resistance. Increased toxicity is also reported when efavirenz and clarithromycin medicines are combined: 46% of patients are reported to have developed a rash.

There is also a lack of information to understand whether ART influences the incidence and severity of paradoxical reactions, and to guide the management of these reactions in patients on ART. Information on management of BU–HIV coinfection has been published in the international medical journal Tropical Medicine & International Health.

The World Health Organization (WHO) has issued preliminary advice on the management of BU–HIV coinfection. However, the process has been limited by the paucity of information upon which to base the guidance, and it is largely extrapolated from the experience of TB–HIV coinfection where significant differences in the risks and benefits of recommendations may apply. This technical update provides more recent advice developed by a panel of clinicians and technical experts, taking into consideration more recent evidence, preliminary data from ongoing management protocols and clinical experience in managing these two diseases.