British <scp>HIV Association</scp> guidelines on the management of opportunistic infection in people living with <scp>HIV</scp>: The clinical management of non‐tuberculous mycobacteria 2024

A wide spectrum of non-tuberculous mycobacteria (NTM) has been reported as isolates from or causes of disease in people living with human immunodeficiency virus (HIV). This is typically in the context of very advanced immunosuppression (CD4 count <50 cells/mm3) in the absence of virological suppression [1] and most individuals have presented with disseminated disease. Effective antiretroviral therapy (ART) has permitted control of viral replication, improvement in immune function and a significant decrease in the incidence of severe opportunistic infections [2-4], including disseminated Mycobacterium avium complex (DMAC) disease [3, 5, 6]. NTM are environmental organisms. Therefore it is important to determine, prior to treatment initiation, whether the organism is the cause of the disease process rather than a reflection of colonisation. With the exception of M. avium complex (MAC), there is limited evidence to guide the choice or duration of treatment and expert opinion should be sought from a clinician experienced in managing mycobacterial disease in the context of HIV or, if not available, in the context of immunosuppression or dissemination. Advice should also be sought from microbiologists (for drug susceptibility testing and interpretation), pharmacists or people with expertise and experience of managing mycobacterial disease in people without HIV. Also with the exception of MAC, most of the recommendations for the treatment of NTM have been extrapolated from trials of treatment for NTM pulmonary disease in individuals without HIV, although some evidence from early trials in populations with advanced HIV disease has added to this guidance. Guidance on supporting people living with HIV with opportunistic infections, including NTM infections, can be found on the British HIV Association (BHIVA) website (https://www.bhiva.org/file/6225e44b53c49/OI-guidelines-supporting-patients.pdf). A full review of these guidelines is due in 2029, with interim updates only if recommendations need updating in line with new data. The scope, purpose and guideline topics were agreed by the writing group. The search (population, intervention, comparator and outcome [PICO]) questions were set and an independent systematic literature review performed. The Medline, Embase and Cochrane Library databases were searched and the literature reviewed to address each question. The PICO questions and search strategies are outlined in Appendix 1. Further details of the methodology can be found on the BHIVA website (https://www.bhiva.org/file/5d514ec9b503d/OI-guidelines-methods-general.pdf), including the use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess and grade the evidence. MAC is the predominant NTM affecting people living with HIV, particularly those with advanced HIV disease and low CD4 counts. MAC organisms are present throughout the environment. Acquisition is via inhalation or ingestion of MAC bacilli through the respiratory or gastrointestinal tracts [7, 8]. No activity is known to predispose to infection, and person-to-person transmission is not believed to occur [9]. Prior to the use of effective ART with virological suppression, DMAC became clinically apparent in 20–40% of individuals with advanced HIV disease [1, 6], although a higher prevalence was detected at autopsy [10]. Since the widespread availability of modern ART, the incidence of DMAC has decreased [2, 5] and the prognosis has improved markedly [5]. In addition, the clinical presentation has changed to include immune reconstitution inflammatory syndrome (IRIS) [11]. DMAC typically occurs in those with advanced immunosuppression who have CD4 counts <50 cells/mm3 without virological suppression. Symptoms are non-specific, and clinical signs and laboratory abnormalities may be similar to those of HIV progression or other HIV-related illnesses. Individuals with DMAC most commonly report fever, night sweats, diarrhoea, abdominal pain, fatigue and anorexia [12, 13]. Common signs include weight loss, hepatomegaly, splenomegaly and lymphadenopathy. Laboratory abnormalities include isolated anaemia or pancytopenia, which may be more severe than expected for the stage of HIV disease [8, 14], leukopenia, elevated alkaline phosphatase levels and hypoalbuminaemia [12, 13]. Radiological features commonly include hepatosplenomegaly and intra-abdominal lymphadenopathy, which were demonstrated in one case series abdominal in of individuals with DMAC or laboratory abnormalities may occur with which can be the clinical presentation in individuals to include and and pulmonary and as new or intra-abdominal disease or system disease with and may also be of of DMAC from or a or from a or as a should be in living with HIV, not on ART, with a CD4 count cells/mm3 and or other of MAC from or in the absence of clinical or features of disseminated infection, is to In some the can be treatment may be these has been by the laboratory and is in in is only reported as very more than of to has been reported as with only of in one The of NTM disease should be in people with low CD4 and bacilli are on although is an important and be in an treatment or organism from or testing from M. is with early and be in people and the of DMAC in of can be one of people with MAC a the to more than mycobacterial to MAC is The is of to mycobacteria by or or the can be detected in a of is with In addition, can MAC mycobacterial has has also been to a to for of MAC from may of from and may organisms or are of is than or it has been to be for the of DMAC of therapy can also be to or other for of MAC or M. rather than for in In the absence of clinical trials also to people without the of guidelines set to and disease for NTM pulmonary isolates which have been by the British is whether NTM disease in people with HIV has the and as in those without HIV, and disease is The and guidelines not address NTM in people living with HIV, who are at higher of and for and clinical may have important for disease and disease. In one in which NTM in people living with HIV was as the NTM should be in with low CD4 count and The of and the of the may also be important in and disease. the of other important are the of and the of present in the A series of trials and in the demonstrated the of MAC with or in the of disease in those with advanced HIV trials of in individuals with advanced HIV disease and CD4 counts cells/mm3 to be effective in the incidence of MAC and of with on in a clinical including with CD4 counts cells/mm3 CD4 counts cells/mm3 and an was effective in the or of MAC disease. and were in trials of similar for DMAC In the by with CD4 counts cells/mm3 were to or or in was found to be more effective than for and as effective as with or a of these was in a clinical in with CD4 counts cells/mm3 was more effective than with the incidence in the with The of and was found to be more effective than with an in and the for isolates were detected of in those with isolates were not detected in those therapy In the absence of a an treatment these and found the of from to the of and were to be and In a Cochrane review of the of MAC individuals with and were to MAC disease than those with No significant in were found those or The availability of effective ART has the of DMAC and people living with HIV of DMAC as a opportunistic This is due to the of immune to MAC of effective ART, in those with severe immunodeficiency and only virological suppression Individuals with CD4 counts <50 cells/mm3 who are ART not MAC not to be at of MAC as reported in clinical trials and in and In trials significant in MAC incidence were found with those a CD4 count <50 cells/mm3 and a to cells/mm3 on the in the by there were of MAC in the with in the in a treatment of In a by in with at one CD4 count <50 cells/mm3 who ART, the incidence of MAC disease was not those and those not In a including with CD4 counts <50 cells/mm3 on ART, incidence of MAC or were of an HIV viral The incidence of MAC on ART was with significant those or not MAC the of with HIV viral No MAC in those with an viral at In a in the of DMAC was the of in individuals with CD4 counts The from in to in with in of DMAC in those ART became case of DMAC was a of in the HIV individuals with CD4 counts <50 cells/mm3 who been on ART for at In a by the incidence of MAC was those ART not MAC CD4 count by at cells/mm3 from and those CD4 counts not The incidence of DMAC was low case those CD4 counts the of and not higher than in those CD4 counts decreased this MAC ART for individuals with low CD4 counts cells/mm3) and is not ART is of and there is to be immune MAC should be in of very low CD4 counts and low of virological suppression, in individuals with a CD4 count <50 HIV and ART to to full virological suppression or ART MAC should also be in individuals with a CD4 count <50 cells/mm3 immune reconstitution is or is to be due to or for those with a new of HIV and who are MAC it is important to and to with the the and of the in and of the the of and the of drug due to in the case of MAC disease or of MAC DMAC and other mycobacterial disease should be prior to through clinical and with of other if clinically with or has been with an incidence of of the respiratory Therefore people with respiratory infections should not be with In the case of or to is an is may be of with virological suppression has been In the treatment of with and with therapy was with in of the literature on treatment is from the or early ART and the of effective ART on are not in these Effective of ART was with a of MAC disease and it has been treatment for DMAC be immune reconstitution has and without effective ART are with of the gastrointestinal in DMAC to the for drug and antiretroviral as as these and other need to be and In a individuals with DMAC treatment were and and and with and there were significant in the of at and in the and there were significant in and in the with and A the of to and not improvement in or although there was a in in the at of of to the of and not and was with higher with of The of and has been with and with the with improved mycobacterial from and improved The of and with and the to be with clinical and has also been in with with or without The in of and to although the not the of in as and the of rather than the of evidence a in the of and a therapy for most people for which is in people with very low CD4 counts and without virological suppression. therapy should include a and a The for be particularly in the of of treatment or in the absence of effective ART, to to is or with and for as or the of drug the and be an susceptibility testing should be on the in case of from in the treatment of MAC disease in the context of immunosuppression or dissemination. also with mycobacterial with to and drug susceptibility rather than has been in MAC pulmonary disease and of the recommendations of the it has also been in some for DMAC there has been with to a HIV from in people without HIV with pulmonary may be be a in to has at similar treatment in MAC with for DMAC in with was at or and at the of was similar in the and the the was due to in of mycobacterial In a were to or with of were low in mycobacterial in of those with may have in of gastrointestinal and is a and with the of and decreased and in the experience of the writing is as the of choice in therapy with In and therapy a of of have been In a of in of of and for to people with MAC The of decreased in and of individuals were in the and at was in the in of individuals who at with and of In a of with with or by was at or The higher of was due to a higher at of or similar in the The of to be as effective as higher and more The of should not although should be to for particularly has been in clinical the has not evidence of A of or reported gastrointestinal with and in the with of in the with the is a more other have been in although trials have been and have in is if there is treatment with are the most to a of and not the in of mycobacterial an with a and in in of although the of a comparator and the of should be an the and an of although of testing should not the use of this drug if should be for in which therapy has been or is not for in the A and not to mycobacterial with the and has been with and with in the of therapy In a in individuals or not as of MAC was the In a with and a in there was comparator use as of therapy has been in case series and as and are in guidelines for the treatment of and have been in for MAC pulmonary disease in people without HIV is in evidence of susceptibility to in MAC The use of has been reported to have to treatment in case of treatment for DMAC as has the use of In guidelines for the treatment of M. is in to of with and a of although there is more experience in MAC pulmonary disease than in DMAC with is evidence for the use of for DMAC in people living with HIV and it is not for this there is a of demonstrated in clinical experience is limited to case of MAC pulmonary and disease in people without HIV may be as of therapy therapy has or is with due to is in evidence of NTM M. it has been in MAC pulmonary disease in individuals without HIV and is as an in this in the guidelines there is only limited experience in the treatment of MAC disease and in in the of disseminated in HIV. only case in which in with other was in MAC disease are in with and and is not in a in in on was with more may be as of therapy therapy has or is with due to has not been in for DMAC of the higher in the by in In added to the of and was with the higher counts in the and of and was not with other DMAC there was with in the by although the therapy was not as effective as the and In the by of a with with a with a and there were more and duration of in the Since has been in the treatment of for people with and without HIV, and there has been although there has not been a of a In the decreased with a in the has not been and is a of for for people with and without HIV The writing it to include with including of in for DMAC or in other in which it is to an effective the of effective ART, of therapy for MAC was although was with a of than those ART with CD4 counts to clinical improvement in MAC disease and evidence of A individuals with DMAC who treatment a of of at of mycobacterial at of ART and CD4 counts a of there was a low incidence of In a in people treatment CD4 count was cells/mm3 with the an HIV and the from and the of a very low of therapy for DMAC was in those with in CD4 counts of of for a of opportunistic infections of of which were for MAC, with a CD4 count of cells/mm3 with of individuals with CD4 counts an HIV the duration of therapy was were one in an was with a CD4 count cells/mm3 and one in an was with a CD4 count cells/mm3 for only with an incidence of MAC of The HIV reported a review of individuals MAC with of of although there were from other causes A of with DMAC on of MAC treatment CD4 counts were a treatment duration of are in and treatment for DMAC can be with very low of at of evidence of effective and ART for and CD4 counts of at With more effective ART, the of the writing in the absence of is with clinical immune reconstitution CD4 count and HIV viral individuals should be to MAC treatment the CD4 count to <50 MAC should be have been trials ART in In of to ART, to the BHIVA antiretroviral treatment which on the only with mycobacterial ART is of in individuals with opportunistic infections also to the BHIVA guidelines for of the of ART in in people who are ART have demonstrated from ART of therapy in those with CD4 counts <50 cells/mm3 it was and not with were those ART, this should be if changed on if there is evidence of virological or to and as as be the in ART for those treatment for the of drug and may be are should be are of and the be of in with or of in with M. is a in the by M. have been with to as this organism in with the is through the and may cause disease in and individuals transmission is not to occur M. is the most cause of NTM disease in the the and in In has the M. of NTM in in In a in the the incidence of M. respiratory isolates was found to be in with in people living with HIV without and in the on the incidence of M. in people living with HIV in the ART are is to the most of NTM to cause disease in people living with HIV, MAC with HIV is one of the most important for M. are the of disease pulmonary pulmonary and and other of immunosuppression treatment and a in who have NTM demonstrated M. pulmonary disease at an stage of HIV and more disease in people without HIV than in other In a more in in and of a low were also found to be independent for the of M. disease M. is with a higher than other of NTM including in people living with HIV In a of for M. infection, of were found in individuals without HIV in those with HIV. ART and for M. have been to be with in people living with HIV with M. pulmonary disease were of a CD4 of ART, and a of mycobacterial MAC M. in people living with HIV more commonly with pulmonary disease than with disseminated features is present in only a of people with HIV by M. and disseminated disease is in those with advanced HIV M. pulmonary disease the of the most are fever, weight and include pain, and with HIV and M. disease present with most commonly and in the and This is in to the presentation in those without HIV and are and with higher CD4 counts there is an of disease. pulmonary disease can with In a of M. disease were found in of people and were the most with or in of The of abnormalities not on the or absence of pulmonary infections or CD4 was the only with Common of disease include and the and with and have also been reported in people with disease can occur and most commonly as with have of and of the is with reported disease is with and reported to the or and of with disseminated disease by M. have been and most commonly in the of pulmonary disease or disseminated The are or in and for and of M. pulmonary disease can be and as the use of may be are with The process of for M. pulmonary disease is the as for M. and at or at be one of or should be M. is a and isolates in of respiratory from individuals without HIV have been found to be clinically in more than of is whether a respiratory for M. in the context of HIV should be clinically some a M. respiratory as an of disease as M. is the most of NTM isolates may disease in the absence of new the of this full of people with a M. from a respiratory with a on whether to therapy on the of the clinical in people in M. is isolated from in the absence of clinical therapy should be In the case of with in those who are a is in the of virological control and a CD4 count the of M. in as and should be clinically have a and for the of NTM infections in people with HIV. In a of individuals by M. were a for clinically and in individuals with and without HIV respiratory and should be as this the most to should be which for with the should be as as and to the should be if than are the use of for of M. is as the including in with HIV prevalence The use of can in the early of NTM M. and should be as an to the available, line are commonly in the and are for the of the most of are for M. there is a of in people living with HIV and are than for M. avium and M. have been reported in the of other of NTM and M. due to the in the A of have been found to be although at a low in those with M. infection, which some of the M. for should not be for M. infection, as this not disease and susceptibility testing of M. isolates should be for only to with treatment for M. there is to and it is in the of In the case of testing which include and for the treatment of M. In of M. are the levels and more than than the for M. the of in susceptibility testing are on M. some isolates of M. may be reported as to at the may isolates are in to higher drug and of to the low of have clinical or as as a is have been clinical trials to the treatment for M. disease and the limited in people living with HIV. has been of in the with a of in those with M. pulmonary disease the of only of people at with in and a need for With occurs the of treatment with treatment and in of if treatment is for at in line with the and guidelines M. with a of including and In with of similar were with of A as or can be as an to is to due to the incidence of with antiretroviral although clinical on are may be as an to to the of particularly in the case of ART including a In the case of or can be by No clinical trials have the duration of treatment for M. pulmonary disease or disseminated disease in people living with HIV. The duration of treatment should be at In the people are not to on the duration of treatment can be as as there has been clinical In pulmonary infections with should be and for treatment to assess the should be in the case of a of clinical and M. can be to the need for and treatment to including drug and of as and of to are In the case of isolates should be a wide of to guide new treatment treatment for with at is effective for the of of M. it has been to be for for has been with with treatment or M. isolates have to as a of therapy have been with a of with and with or or for the by or for a of is or for disseminated M. disease. than of NTM cause human disease have been the most important of which are MAC and M. the the most infections in people living with HIV include M. M. M. M. and M. with MAC and M. immunosuppression due to HIV one of the most important for with of In a series of NTM infections in were in people living with HIV, of CD4 counts <50 cells/mm3 In a similar series from of NTM infections were in people living with HIV In the prevalence of NTM people living with HIV was at with ART of NTM In the prevalence of NTM in people living with HIV with mycobacterial was with a of NTM with CD4 counts In a from of mycobacterial isolated from people living with HIV were as with NTM with CD4 counts cells/mm3 In the the incidence of NTM in people living with HIV from laboratory was at to in people with a CD4 count <50 cells/mm3 case of NTM people living with HIV, only were from people with CD4 counts cells/mm3 to the spectrum of and clinical it is to the and with NTM is of people living with HIV who have NTM has markedly with the of in an case series reported in in the of people with M. infections who were living with HIV by with a case series of M. infections in individuals who were living with HIV, from in and the of ART, reported markedly of at and at infections for to of NTM isolates in clinical although there is as to whether the of NTM in respiratory or in a series of NTM isolates from people and than of NTM were with human and only a with pulmonary isolates for NTM disease In the only of people with NTM isolated from to with for NTM pulmonary disease infections with NTM isolated from have also been of NTM from was in of individuals in a case series A wide of other are also in case series and case including and M. is particularly with complex gastrointestinal including it is important to be NTM is also in the presentation of in people who are living with HIV there is evidence on which to on the and treatment of with of The literature review for these guidelines NTM disease. case case as prevalence or incidence and with other The of opinion or other not present or than of were with NTM in people living with the of these were case were or from a of with NTM it is important to be not for of susceptibility to there is a clinical of drug testing should be on susceptibility testing is this should at a testing for to and should be rather than and should be reported rather than of or This is in line with recommendations for the and treatment of NTM pulmonary infections in the are of or to recommendations for or treatment of with of The should be without other than drug testing should be on NTM isolates to be of clinical and should be to a or expert to with NTM are and include a or as the most with and a is also This the drug have been of to and have been In some of to and to have also been reported M. is particularly as an organism is important to the M. and are known to have the for to due to the of the is also present in M. in a may be for a of M. infections, of the should be in to of susceptibility to with in the case of an of are systematic to guide duration of treatment are and may be in people with of of clinical and a of treatment from of although this is and to is not in disease. The writing of and and for and The writing also and of for this The Medline, Embase and Cochrane Library databases were searched the or mycobacterial infections, Mycobacterium avium Mycobacterium avium or Mycobacterium were limited to and the of the from on and HIV and of and were also of of therapy