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Opportunistic Volume 26 Issue 3 September 2018

Perspective Recurring and Emerging Questions Related to Management of HIV-Related Opportunistic Infections

The of HIV-related opportunistic infections (OIs) has dramatically Society of America (IDSA) OI guide- declined with the ability to achieve viral suppression and immune recon- lines are accessed online. During the stitution with potent antiretroviral therapy. However, a large number of period from March 1, 2017, to Feb- patients remain at risk for OIs because they are diagnosed at late stages of ruary 28, 2018, adult OI guidelines HIV disease, fail to stay in treatment, or fail to maintain viral suppression. were accessed more than 420,000 Clinicians should remain vigilant for OIs and for changes in recommended times; of these, approximately 72,000 management strategies. Issues that often arise in this regard include how to page views were for Pneumocystis interpret polymerase chain reaction diagnostic results in individuals with HIV jiroveci (PCP), 45,000 for ; whether primary prophylaxis for Mycobacterium avium complex drug dosing, 28,000 for is still needed; whether clinicians should screen asymptomatic patients for , and 25,000 for Myco- cryptococcal antigen; and need for amphotericin B in treatment regimens bacterium avium complex (MAC). for cryptococcal . This article summarizes a presentation by Henry Masur, MD, at the IAS–USA continuing education program held in Washing- Most-Asked Questions about OIs ton, DC, in April 2018. Very few controlled trials related to Keywords: HIV, opportunistic infections, , PCP, Myco- the diagnosis, therapy, or prevention bacterium avium, MAC, Toxoplasma, cryptococcal meningitis, PCR, diagnostics of OIs are currently being performed, in contrast to the numerous studies Despite the success of current anti- approximately 1100 to approximately performed in the 1980s and 1990s. The retroviral therapy (ART) in reducing 350 over the last 10 years. However, guidelines currently rely on observa- the burden of HIV-related opportunis- the and incidence in this tional data from patients with HIV tic infections (OIs), a large number of district remain unacceptably high. As infection, and experience in other individuals living with HIV infection of 2016, the overall prevalence of HIV patient populations that are plausibly present late in HIV disease or do not infection was 1.9%, including rates of applicable to patients with HIV infec- maintain viral suppression and thus 0.9% among whites, 3.1% among Afri- tion. Thus some of the recent changes remain at risk for opportunistic dis- can Americans, and 1.2% among His- in the guidelines are based on obser- eases. Management of OIs is thus still panics/Latinos. Data from 2016 indicate vational data from patients with HIV relevant for practitioners who care for that among individuals with known infection, and some of the recommen- this patient population. HIV infection, only 63% are virally sup- dations are extrapolated from other pressed, with only 47% of youth with patient populations. HIV in Washington, DC HIV infection being virally suppressed (Figure 1). Thus, there remains a large Polymerase Chain Reaction (PCR)- Based Diagnosis The current state of the HIV epidemic patient population with low or declin- in Washington, DC, provides an exam- ing CD4+ cell counts who are suscep- For the management of HIV-related ple of the ongoing risk of OIs in current tible to OIs. From 2011 to 2015, 21% of OIs, clinicians must be aware that patient populations. The good news in newly diagnosed individuals had CD4+ microbiology laboratories are changing Washington, DC, is that, thanks to the cell counts below 200/µL at diagnosis; their testing platforms dramatically. efforts of many funding agencies, fed- at 1 year after diagnosis, 50% of these When organisms are grown in conven- eral and local health administrations, patients still had counts below 200/µL. tional media, any growth can often clinics and hospitals, and health care be identified by genus and species practitioners, the annual number of within a few hours by techniques such newly recognized cases of HIV infection Surrogate Markers for Incidence of OIs in Recent Years as Matrix Assisted Laser Desorption/ in this district has been reduced from Ionization/Time of Flight Mass Spec- In the absence of hard data on inci- trometry (MALDI-TOF) Other speci- Dr Masur is Clinical Professor of Medicine dence of OIs in recent years, there are mens are tested by qualitative nucleic at George Washington University School of some indices that can provide an idea acid amplification methods that are Medicine in Washington, DC. He is Cochair of the scope of the problem of HIV- extremely sensitive for minute quan- of the National Institutes of Health-Centers for Disease Control and Prevention-Infec- related OIs. One such metric is how tities of organisms and are highly tious Disease Society of America Guidelines often the National Institutes of Health specific for identifying organisms for the Management of HIV-Related Oppor- (NIH)-Centers for Disease Control and accurately. Thus, the clinician is get- tunistic Infections in Adults and Adolescents. Prevention (CDC)-Infectious Disease ting information faster, and can obtain

79 IAS–USA Topics in Antiviral Medicine

14,000 500 450 12,000 400 10,000 350 300 8,000 250 6,000 200 Number of Cases 4,000 Number of Youths 150 100 2,000 50 0 0 Living Ever linked to Retained in Retained in Virally Living Ever linked to Retained in Retained in Ever virally Virally in DC HIV care any care in any care in supressed in in DC HIV care any care in any care in supressed supressed in (98%) 2016 (76%) 2016: >1 2016 (63%) (95%) 2016 (77%) 2016: >1 (57%) 2016 (47%) medical visit medical visit (56%) (53%)

Figure 1. Contact with HIV care and viral suppression among known individuals (left) and youth (right) with HIV infection in Washington, DC (DC) in 2016. Adapted from the DC Health Annual Epidemiology and Surveillance Report, 2017.10 far more sensitive testing, often with is a nasopharyngeal swab (not nasal contaminate lower respiratory speci- concurrent information about whether swab) so that cells in the posterior mens) with respiratory , or with specific resistance-associated genes retropharynx are collected. The Bio- MAC, Cryptococcus, or Pneumocystis. are present. Thus, the data coming to fire upper respiratory panel tests for a Thus, because PCR is ultrasensitive clinicians must be interpreted with number of such as Bordetella, compared with conventional smears analytic approaches that are consider- Chlamydophila pneumonia, and Myco- and cultures, a negative PCR test is con- ably different from interpretations that plasma pneumonia, and several viruses vincing evidence that the is clinicians made when diagnoses were such as , parainfluenza, coro- not present. A positive result, however, established based on smears of bio- navirus and adenovirus. If the speci- must be evaluated in the context of the logic fluids and tissues, conventional men is positive for coronavirus, for clinical situation, and what other path- cultures, antigen detection assays, and example, how much confidence is there ogens or processes are concurrently serum antibody tests. For example, that the identified agent is the cause of present. Some that can col- increasingly, laboratories are not per- the patient’s syndrome? onize the airways of an individual with forming immunofluorescence assays Coronavirus may be present in very HIV infection, including herpes simplex for PCP, with diagnoses being primarily small quantities and represent coloniza- , (CMV), MAC, and based on PCR assays. tion following an acute infection days , are so rarely the cause of pul- The question is whether the detec- or weeks before, depending on the monary dysfunction in persons with tion of an organism in respiratory sam- patient’s immune status (ie, some HIV infection, even those with very low ple, stool, cerebrospinal fluid (CSF), or immunosuppressed persons can shed CD4+ cell counts, that they should be blood is an indication that the identi- a respiratory virus for many months considered as extremely unlikely etio- fied organism is causing the syndrome after an acute infection). If coronavirus logic agents for pulmonary dysfunction. of concern rather than being detected is the only pathogen detected, the cli- Conventional cultures can detect as a bystander/colonizer or contami- nician might assume that coronavirus colonizers as well, but conventional nant. For instance, when bronchoalve- has caused the clinical illness, assum- cultures are not as sensitive as PCR. olar lavage fluid is tested by the Biofire ing the clinical illness is compatible Thus, when the cultures are positive, Platform (Salt Lake City, Utah), does the with what is known about a corona- the quantity of organisms present is detection of an organism provide the virus infection. However, the patient more likely to indicate causality; the clinician with assurance that Pneumo- may in fact be infected with an organ- same is true for a smear. In addition, in cystis is the causative organism? ism not tested for by this platform, or contrast to PCR, conventional cultures Consider a scenario in which a 35- missed by this specimen or by a pro- can be quantitative or semiquantitative, year-old patient recently diagnosed cess that is not due to an infection. and can be interpreted in association with HIV infection has a nadir CD4+ For lower respiratory panels, there with smears. cell count of 90/μL and is on dolute- are similar difficulties with interpreta As an example of the diagnostic gravir-based ART, and presents with tion of these sensitive detection sys- uncertainty associated with multiplex low-grade fever and cough. For the Bio- tems. Patients may have coloniza- results, consider a patient who looks fire 2 panel, the appropriate specimen tion in their lower respiratory tracts toxic, has diffuse bilateral infiltrates, to detect upper respiratory pathogens (or in upper respiratory secretions and has an oxygen saturation level of

80 Opportunistic Infections Volume 26 Issue 3 September 2018

91% on room air. A pulmonologist per- 1200 forms bronchoalveolar lavage and a lower respiratory tract PCR panel is ● 1000 ● ordered. If the result comes back as ● ● ● ● positive for Pneumocystis, CMV, Cryp- 800 ▼ ▼ tococcus, Toxoplasma, or coronavirus, ▼ ▼ ▼ ▼ ● which would be convincing as the cause 600 ● of the patient’s pulmonary pathology? ▼ ● ▼ Although any of these organisms could ▲ ▼● 400 ▲ ▲ ▲ ▲ ▲ be the cause of the pulmonary dys- ■ ■ ▲ ▼ function, the most suggestive finding ■ ▲● ▼ 200 ◆■ ▲ ● ◆ ◆ ◆ ■ ▲ ● Incidence per 100,000 Person-Years ● ●■ ●■ ● ▲ would be Toxoplasma, because it is ◆ ◆ ◆ ◆● ◆● ◆● ● ◆ ◆ ◆ ◆■ ◆■ ■ ■ the only organism among these that ◆ ◆ ◆ ◆ ◆● 0 is not ordinarily found in the respira- 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 tory tract as a latent organism. CMV Year and coronavirus are rarely the cause of ● Pneumocystis jiroveci pneumonia ◆ Cryptococcus serious lower respiratory tract infection ▼ ◆ Toxoplasmosis in individuals with HIV infection. Cryp- ▲ Mycobacterium avium complex or M kanasii ● Cytomegalovirus retinitis tococcus is not common, but would be ■ Pulmonary tuberculosis a consideration. Pneumocystis, as men- tioned above, could be the cause of the Figure 2. NA-ACCORD (North American AIDS Cohort Collaboration on Research and De- pulmonary dysfunction or could be col- sign) data on incidence of HIV-related opportunistic infections in 2000 to 2010 in the United onizing the respiratory tract. States and Canada (n=63,541). Adapted from Buchacz et al.4 Thus, as we evolve into the era of PCR diagnostics, guidelines are strug- load falls below the level of laboratory potent combination ART era. Although gling with how to make a diagnosis for detection, the degree of immunoin- not exhibiting as great a decline as Pneumocystis if the laboratory does not competence is diminished substan- PCP, the incidence of MAC was reduced perform immunofluorescence. Similar tially, even if the CD4+ cell count has by approximately 45% between 2000 4 considerations apply to the detection not risen substantially. However, deter- and 2010. of other bacteria, viruses, fungi, and mining when OI prophylaxis can be Data from HOPS (HIV Outpatient in these multiplex panels. Cli- stopped has been difficult if one is Study) suggests that the risk of MAC is nicians need to be cognizant of what using viral load and CD4+ cell count low among patients on ART who have tests the laboratory is performing when as interacting factors. nadir CD4+ cell counts below 50/µL, they interpret report the presence of Guidelines and most experts still even in the absence of primary pro- 5 organisms in a biologic specimen. advocate using CD4+ cell count crite- phylaxis. Of special interest, among Multiplex PCR platforms are cur- ria for stopping and starting OI pro- patients in the study with CD4+ cell rently being used by many diagnostic phylaxis. OI prophylaxis is especially counts below this threshold who were laboratories for stool, CSF, and blood. important for patients with low CD4+ started on ART, there were no cases of Some platforms also detect the pres- cell counts who take their medications MAC among 41 who did not receive pro- ence of resistance-associated genes for regularly, but who have drug-resistant phylaxis nor among 30 who did. This certain pathogens, such as mecA and virus and thus low CD4+ cell counts is a small sample size, but it illustrates mecC for methicillin-resistant Staphy- and high viral loads. the dearth of cases in most observa- lococcus aureus. As with respiratory There have been few changes in rec- tional studies. specimens, the issue for clinicians will ommendations for prophylaxis except The uncommon individuals with HIV be how to determine if the presence of for the recommendations for MAC. The infection who do develop disseminated a pathogen qualitatively (with no quan- current IAS-USA guidelines1,2 do not MAC today have much better survival titation) is convincing evidence of the recommend primary MAC prophylaxis than they would have 1 or 2 decades need to treat the organisms identified. for individuals on effective ART, and ago, which is not unexpected given the NIH-CDC-IDSA guidelines3 do cur- the efficacy of current ART. Data from San Francisco show declining mortal- MAC Prophylaxis rently, as of August 2018, recommend such prophylaxis. The latter guidelines ity from AIDS-defining OIs, including The use of for the are likely to change in the very near MAC, with the advent of potent combi- prevention of OIs is still an important future on the basis of accumulating nation ART, with many patients having component of HIV care. However, observational evidence about the rare long-term survival after MAC diagno- 6 patients will rarely take OI prophylaxis occurrence of MAC in the current era. sis (Figure 3). Based on the facts that without also taking ART. For patients As shown in Figure 2, data through 2010 there is a lower incidence of MAC in this who respond to ART, once the viral show the decline in OIs during the country, that those who start ART

81 IAS–USA Topics in Antiviral Medicine

Pneumocystis pneumonia Kaposi sarcoma HIV wasting syndrome 1.0 1.0 1.0

0.8 0.8 0.8

0.6 0.6 0.6

0.4 0.4 0.4 Survival Probability Survival 0.2 Probability Survival 0.2 Probability Survival 0.2

0 0 0 0 5 10 15 20 25 30 0 5 10 15 20 25 30 0 5 10 15 20 25 30 Years After Diagnosis Years After Diagnosis Years After Diagnosis

Esophageal candidiasis Mycobacterium avium complex HIV encephalopathy 1.0 1.0 1.0

0.8 0.8 0.8

0.6 0.6 0.6

0.4 0.4 0.4

Survival Probability Survival 0.2 Probability Survival 0.2 Probability Survival 0.2

0 0 0 0 5 10 15 20 25 30 0 5 10 15 20 25 30 0 5 10 15 20 25 30 Years After Diagnosis Years After Diagnosis Years After Diagnosis

Period: Pre-antiretroviral treatment (ART) Mono-/Dual-ART Combination ART

Figure 3. Survival after diagnosis of selected AIDS-defining opportunistic infections in San Francisco, California, 1981 to 2012 (n=20,858). Adapted from Djawe et al.6 appear to have low risk of MAC disease counts below 100/µL, whereas NIH- clinicians would choose to treat with whether on prophylaxis or not, and CDC-IDSA guidelines leave screening ART alone. Others would treat with ART that we are managing the disease bet- to the discretion of practitioners. Most plus fluconazole. If the CSF antigen is ter, the NIH, CDC, and IDSA will likely practitioners in the United States do positive, liposomal amphotericin B plus also soon recommend that no primary not perform such screening. The prac- flucytosine is the regimen of choice. MAC prophylaxis is needed if effective tice of US practitioners likely reflects Thus there remains uncertainty re- ART is initiated and viral suppression the finding that in the United States, the garding screening in the United States. is achieved. frequency of asymptomatic cryptococ- Potential advantages of screening in- It is also important to note that the cal antigenemia is low: approximately clude the fact that earlier cryptococcal incidence of disseminated MAC in this 2.9% of asymptomatic patients with a meningitis treatment leads to better era can be confounded by cases of im- CD4+ cell count below 100/µL and outcomes and that risk of IRIS is re- mune reconstitution syndrome (IRIS) 4.6% with CD4+ cell counts below 50/ duced by treating cryptococcal dis- that are associated with lymph node or µL have a positive cryptococcal anti- ease for 2 to 8 weeks before starting other culture-positive tissue, ie, some gen test. The range of antigen titers ART. To date, there is very little evi- definitions of disseminated MAC may observed in these cases spans from dence in the United States that survival include positive blood cultures for MAC. very low to impressively high. Some among asymptomatic patients is bet- Incidence and mortality data need to be patients do develop a syndrome fol- ter with prospective monitoring than carefully assessed to determine what lowing initiation of ART that may be with a strategy that initiates treatment patient population is being described, related to Cryptococcus, but it is also when patients have manifestations due ie, only those with positive blood cul- hard to determine whether this disease to active cryptococcal disease. These tures, or those with positive cultures is related to active organism replica- manifestations might include fever, only from sites other than blood who tion, or if it is IRIS. headache, or more obvious presenta- may have IRIS. If screening for asymptomatic cryp- tions of meningitis, , or other tococcal antigen is done, and a positive organ involvement. Screening for Cryptococcal Antigen result is obtained, a lumbar puncture at CD4+ Cell Counts Below 100/µL should be performed to determine if the Does Amphotericin B Need to be Used The World Health Organization rec- patient has asymptomatic meningeal in Cryptococcal Meningitis? ommends screening for cryptococcal infection. If the patient has a negative Another frequently asked question antigen in patients with CD4+ cell CSF cryptococcal antigen test, some regarding cryptococcal disease is

82 Opportunistic Infections Volume 26 Issue 3 September 2018

whether there are recommended regi- CD4+ cell counts over 200/uL, al- second episodes. Treatment-limiting mens for cryptococcal meningitis that though their immunologic response toxicity of TMP-SMX was observed in do not include liposomal amphotericin is not as robust as individuals without 6 patients (7%). A small comparative B. Azole drugs are fungistatic, whereas HIV infection. trial reported in 1998 showed no dif- amphotericin B is fungicidal. It has A newer recombinant adjuvant ference in progression rates between been demonstrated that there is a vaccine has become available—a 35 patients receiving pyrimethamine- good correlation between outcome of 2-dose subunit vaccine containing sulfadiazine (14%) and 37 receiving disease and reduction in CSF crypto- recombinant glycoprotein E in combi- TMP-SMX (16%).9 coccal titers. A number of studies have nation with a novel adjuvant. It is 68% The regimens of choice for toxoplas- examined whether higher doses of effective for reducing the occurrence mosis based on extent and quality of azoles can be as effective as ampho- of clinical varicella zoster virus infec- evidence remain pyrimethamine plus tericin B. A study reported at the 2018 tion in post-hematopoietic stem cell sulfadiazine (plus leucovorin) or pyri- Conference on and Oppor- transplant recipients. However, there methamine plus clindamycin (plus leu- tunistic Infections showed that increas- are very limited data in HIV infection, covorin). If pyrimethamine is not avail- ing fluconazole doses as high as 2000 with 2 small studies having assessed able, TMP-SMX is the highest-rated mg/day did not provide the same CSF safety and immunologic response, but alternative. TMP-SMX has the addi- clearance rate as amphotericin B. The not clinical efficacy. Whether this vac- tional advantage that it can be given proportions of patients with negative cine will become the recommended intravenously, an advantage for seri- CSF cultures at week 10 were 45%, immunization for individuals with HIV ously ill patients. Pyrimethamine can- 56%, and 60% with fluconazole doses of infection with CD4+ cell counts below not be administered parenterally. 1200, 1600, and 2000 mg/day, respec- or above 200/uL is unknown. The use Atovaquone is not quite as reliable as tively, compared with 81% with ampho- of this vaccine seems plausible because sulfadiazine-pyrimethamine, because tericin B treatment.7 it is not a live virus vaccine. However, the time to steady state levels is 3 to 4 Thus, in the United States, it con- the effect of the adjuvant has not been days and absorption can be erratic if tinues to be recommended that an studied in this population, nor has the the patient is not taking a high-fat diet. amphotericin-based regimen be used clinical efficacy been established. Atovaquone with or without another in all cases of cryptococcal meningitis Similarly, there are no robust effi- drug is adequate but not considered to (fluconazole alone can be used for non- cacy data for the new adjuvanted hepa- be as effective as TMP-SMX. meningeal disease). Liposomal ampho- titis B vaccine, nor are there extensive tericin plus flucytosine is the most safety data in the population with HIV Is Hepatitis A an OI? rapidly fungicidal regimen. Ampho- infection for this adjuvanted product. An outbreak of hepatitis A infection tericin B plus fluconazole is also recom- Thus, at this time this new vaccine is began in San Diego County in Califor- mended as an alternative regimen, not recommended for populations with nia in November­ 2016 and spread to exhibiting similar mortality rate but HIV infection, although there is no evi- Santa Cruz, Los Angeles, and Monterey slower CSF sterilization. dence at this time that the vaccine is Counties, and now to several other There is also debate about whether harmful or less effective than the cur- states. On this basis, there have been corticosteroid therapy should be used rent product. many questions regarding whether empirically when starting therapy for hepatitis A is an HIV-related OI. There cryptococcal meningitis. One study has Treatment for Toxoplasma was a report of 704 cases of hepatitis Encephalitis shown a higher rate of poor outcomes A virus infection in this outbreak, with and adverse events when dexametha- A common question regarding treat- 461 hospitalizations and 21 deaths. sone was added to amphotericin B ment for Toxoplasma encephalitis is: Although some cases occurred in plus fluconazole. Thus, empiric cortico- If pyrimethamine is either unavailable patients with HIV infection, the epide- steroids in the absence of evidence of from suppliers or too costly for insur- miologic association with acquisition increased intracranial pressure are not ance plans, is trimethoprim-sulfameth- was poor sanitation in the context of recommended. oxazole (TMP-SMX) an appropriate ini- homelessness and among individu- tial therapy. And: Is TMP-SMX superior als who use injection drugs. Presence Which Varicella Zoster Virus Vaccine to atovaquone? of hepatitis B virus and hepatitis C Is Recommended Data from an observational trial virus, but not HIV infection, were cor- Another frequently asked question reported in 2009 showed good results related with morbidity and mortality. is whether a recently developed var- with TMP-SMX that appeared based Thus, hepatitis A is not considered icella zoster virus vaccine should be on small numbers of cases to be an HIV-associated OI and is unlikely used in individuals with HIV infec- comparable with those reported for to be featured in OI guidelines. How- tion. The previous live attenuated pyrimethamine.8 Clinical response ever, hepatitis A immunization should vaccine is contraindicated in patients was observed overall in 77 (93%) of be offered to all individuals with HIV with CD4+ cell counts below 200/µL. 83 patients, including response in 26 infection who are seronegative for It is recommended for patients with of 28 patients who were retreated for antibody to hepatitis A virus. 83 IAS–USA Topics in Antiviral Medicine

Conclusion Francisco, 1981-2012. J Infect Dis. 2015; References 212(9):1366-1375. OIs remain a major challenge for in- 7. Lalloo UG, Larsen R, Aberg J, et al. Higher dividuals with HIV infection. A sub- 1. Günthard HF, Saag MS, Benson CA, et al. high dose fluconazole for the treatment Antiretroviral drugs for treatment and of cryptococcal meningitis. [CROI Ab- stantial number of people in the United prevention of HIV infection in adults: stract 35]. In Special Issue: Abstracts From States continue to present with 1 or 2016 recommendations of the Interna- the 2018 Conference on Retroviruses tional Antiviral Society-USA panel. JAMA. and Opportunistic Infections. Top Antivir more OIs as the initial manifestation of 2016;316(2):191-210. Med. 2018;26(suppl 1):1-483. their HIV infection. A substantial num- 2. Saag MS, Benson CA, Gandhi RT, et al. 8. Beraud G, Pierre-Francois S, Foltzer A, et ber of individuals with HIV infection Antiretroviral drugs for treatment and al. Cotrimoxazole for treatment of cere- prevention of HIV infection in adults: bral toxoplasmosis: an observational co- are not in continuous care and do not 2016 recommendations of the Interna- hort study during 1994-2006. Am J Trop have durable viral suppression. tional Antiviral Society-USA Panel. JAMA. Med Hyg. 2009;80(4):583-587. Although new antifungal and anti- 2018;320(4):379-396. 9. Torre D, Casari S, Speranza F, et al. Randomized trial of trimethoprim-sul- herpes virus drugs and new immuni- 3. Panel on Opportunistic Infections in HIV- Infected Adults and Adolescents. Guide- famethoxazole versus pyrimethamine- zations are becoming available, few lines for the prevention and treatment of sulfadiazine for therapy of toxoplasmic of them have been assessed in popu- opportunistic infections in HIV-infected encephalitis in patients with AIDS. Italian adults and adolescents. https://aidsinfo. Collaborative Study Group. Antimicrob lations with HIV infection in robust nih.gov/guidelines/html/4/adult-and- Agents Chemother. 1998;42(6):1346-1349. controlled trials. Thus, updates of guide- adolescent-opportunistic-infection/0. Ac- 10. DC Health. Annual Epidemiology and Sur- cessed on July 16, 2018. veillance Report 2017. https://dchealth. lines for management of OIs in indi- dc.gov/sites/default/files/dc/sites/doh/ viduals with HIV infection in terms of 4. Buchacz K, Lau B, Jing Y, et al. Incidence publication/attachments/HAHSTA%20 of AIDS-defining opportunistic infections prevention or therapy will have to rely Annual%20Report%202017%20-%20 in a multicohort analysis of HIV-infected Final%20%282%29.pdf. Accessed on June on observational studies of individuals persons in the United States and Cana- 29, 2018. da, 2000-2010. J Infect Dis. 2016;214(6): with HIV infection and plausible infer- 862-872. ences from other populations. ( ) 5. Yangco BG, Buchacz K, Baker R, Palella Top Antivir Med. 2018;26 3 :79-84. Presented by Dr Masur in April 2018. First FJ, Armon C, Brooks JT. Is primary myco- ©2018, IAS–USA. All rights reserved draft prepared from transcripts by Matthew bacterium avium complex prophylaxis necessary in patients with CD4 <50 Stenger. Reviewed and edited by Dr Masur in cells/muL who are virologically sup- September 2018. pressed on cART? AIDS Patient Care STDS. 2014;28(6):280-283. Financial affiliations in the past 12 months: 6. Djawe K, Buchacz K, Hsu L, et al. Mortal- Dr Masur has no relevant financial affilia- ity risk after AIDS-defining opportunistic tions to disclose. illness among HIV-infected persons--San

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