The pathogenesis of increasing drug resistance among patients with multidrug-resistant or extensively drug-resistant tuberculosis undergoing treatment is poorly understood. Increasing drug resistance found among Mycobacterium tuberculosis recovered from cavitary isolates compared with paired sputum isolates suggests pulmonary cavities may play a role in the development of worsening tuberculosis drug resistance.

The pathogenesis of increasing drug resistance among patients with multidrug-resistant or extensively drug-resistant tuberculosis undergoing treatment is poorly understood. Increasing drug resistance found among Mycobacterium tuberculosis recovered from cavitary isolates compared with paired sputum isolates suggests pulmonary cavities may play a role in the development of worsening tuberculosis drug resistance.

This randomized trial determined that Staphylococcus aureus eradication did not differ when decolonization was performed by all household members versus the index case alone. However, subsequent skin and soft tissue infections were reduced in cases and household contacts assigned to the household decolonization group.

(See the Editorial Commentary by Miller, on pages 752–4.)

Background. Community-associated Staphylococcus aureus infections often affect multiple members of a household. We compared 2 approaches to S. aureus eradication: decolonizing the entire household versus decolonizing the index case alone.

Methods. An open-label, randomized trial enrolled 183 pediatric patients (cases) with community-onset S. aureus skin abscesses and colonization of anterior nares, axillae, or inguinal folds from 2008 to 2009 at primary and tertiary centers. Participants were randomized to decolonization of the case alone (index group) or of all household members (household group). The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily chlorhexidine body washes. Colonization of cases and subsequent skin and soft tissue infection (SSTI) in cases and household contacts were ascertained at 1, 3, 6, and 12 months.

Results. Among 147 cases with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 50% of cases in the index group and 51% in the household group (P = 1.00). Among 126 cases completing 12-month follow-up, S. aureus was eradicated from 54% of the index group versus 66% of the household group (P = .28). Over 12 months, recurrent SSTI was reported in 72% of cases in the index group and 52% in the household group (P = .02). SSTI incidence in household contacts was significantly lower in the household versus index group during the first 6 months; this trend continued at 12 months.

Conclusions. Household decolonization was not more effective than individual decolonization in eradicating community-associated S. aureus carriage from cases. However, household decolonization reduced the incidence of subsequent SSTI in cases and their household contacts.

Clinical Trials Registration. NCT00731783.

Through analytic synthesis of data from observational cohorts of healthcare providers from the 1920s through the 1950s, we estimate that individuals with latent tuberculosis have a 79% lower risk of tuberculosis disease following reinfection compared with initial infection.

(See the Editorial Commentary by Vernon and Villarino, on pages 792–3.)

Background. The risk of progression to active tuberculosis is greatest in the several years following initial infection. The extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. Indirect estimates from population models have been highly variable.

Methods. We reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of latent tuberculosis to estimate the incidence of tuberculosis among individuals with latent tuberculosis infection (LTBI group) and without latent tuberculosis (uninfected; UI group). We calculated the incidence rate ratio (IRR) of tuberculosis disease following infection between these 2 groups. We then adjusted incidence for expected reactivation, proportion of each group that was infected, and median time of observation following infection during the study.

Results. We identified 18 publications reporting tuberculosis incidence among 23 paired cohorts of individuals with and without latent infection (total N = 19 886). The weighted mean adjusted incidence rate of tuberculosis in the LTBI and UI groups attributable to reinfection was 13.5 per 1000 person-years (95% confidence interval [CI]: 5.0–26.2 per 1000 person-years) and that attributable to primary infection was 60.1 per 1000 person-years (95% CI: 38.6–87.4 per 1000 person-years). The adjusted IRR for tuberculosis in the LTBI group compared with the UI group was 0.21 (95% CI: .14–.30).

Conclusions. Individuals with latent tuberculosis had 79% lower risk of progressive tuberculosis after reinfection than uninfected individuals. The risk reduction estimated in this study is greater than most previous estimates made through population models.

Streptococcus pneumoniae strains expressing serotype 11E commonly occur among disease isolates, rarely occur among carriage isolates, and are clonally unrelated. Thus, 11E strains seem to have emerged after dissemination of serotype 11A progenitors to deeper tissues outside the nasopharynx.

Background. Streptococcus pneumoniae is a commensal colonizer of the human nasopharynx (NP) that causes disease after evasion of host defenses and dissemination. Pneumococcal strains expressing the newly identified serotype 11E arise from antigenically similar 11A progenitors by genetic inactivation of the O-acetyltransferase gene wcjE. Each 11E strain contains a distinct mutation to wcjE, suggesting that 11E strains are not transmitted among hosts despite their recovery from multiple patients with pneumococcal disease. We investigated whether the presumed lack of transmission of serotype 11E is consistent with its inability to survive in the NP.

Methods. More than 400 pneumococcal carriage, middle ear, conjunctiva, and blood isolates, serotyped as 11A by Quellung reaction, were reexamined for reactivity to 11A- and 11E-specific antibodies. We confirmed serotyping of isolates with sequencing of wcjE alleles.

Results. Serotype 11E strains were statistically more likely to occur among blood (4 of 15), conjunctiva (1 of 14), or middle ear (2 of 21) isolates than among carriage isolates (2 of 355). All 11E isolates contained unique mutations that putatively decrease wcjE expression.

Conclusions. The lack of a circulating 11E clone and the increased occurrence of 11E strains among disease isolates supports the idea that serotype 11E independently arises during infection after initial colonization with a serotype 11A progenitor. Factors encountered in the NP likely contribute to relative rarity of 11E among carriage isolates, whereas selective pressures in deeper tissues possibly promote 11E emergence. These findings illustrate a novel model of microevolution that transpires during the span of a single encounter with serotype 11A, highlighting the adaptability of bacterial pathogens within hosts.

In a prospective study, human immunodeficiency virus (HIV)–infected patients with pneumococcal pneumonia had nasopharyngeal colonization densities 5 log10 higher than those in concurrently identified HIV-infected asymptomatic controls, as measured by real-time polymerase chain reaction (rtPCR). A nasopharyngeal lytA density of ≥8000 copies/mL at rtPCR may be a useful diagnostic marker for pneumococcal pneumonia.

Background. There is major need for a more sensitive assay for the diagnosis of pneumococcal community-acquired pneumonia (CAP). We hypothesized that pneumococcal nasopharyngeal (NP) proliferation may lead to microaspiration followed by pneumonia. We therefore tested a quantitative lytA real-time polymerase chain reaction (rtPCR) on NP swab samples from patients with pneumonia and controls.

Methods. In the absence of a sensitive reference standard, a composite diagnostic standard for pneumococcal pneumonia was considered positive in South African human immunodeficiency virus (HIV)–infected adults hospitalized with radiographically confirmed CAP, if blood culture, induced good-quality sputum culture, Gram stain, or urinary Binax demonstrated pneumococci. Results of quantitative lytA rtPCR in NP swab samples were compared with quantitative colony counts in patients with CAP and 300 HIV-infected asymptomatic controls.

Results. Pneumococci were the leading pathogen identified in 76 of 280 patients with CAP (27.1%) using the composite diagnostic standard. NP colonization density measured by lytA rtPCR correlated with quantitative cultures (r = 0.67; P < .001). The mean lytA rtPCR copy number in patients with pneumococcal pneumonia was 6.0 log10 copies/mL, compared with patients with CAP outside the composite standard (2.7 log10 copies/mL; P < .001) and asymptomatic controls (0.8 log10 copies/mL; P < .001). A lytA rtPCR density ≥8000 copies/mL had a sensitivity of 82.2% and a specificity of 92.0% for distinguishing pneumococcal CAP from asymptomatic colonization. The proportion of CAP cases attributable to pneumococcus increased from 27.1% to 52.5% using that cutoff.

Conclusions. A rapid molecular assay of NP pneumococcal density performed on an easily available specimen may significantly increase pneumococcal pneumonia diagnoses in adults.

We performed a retrospective comparison of ceftriaxone versus oxacillin for osteoarticular infections due to methicillin-sensitive Staphylococcus aureus. Clinical outcomes did not differ between treatment groups. Antibiotic toxicity was more common in patients receiving oxacillin.

Background. Antistaphylococcal penicillins are the treatment of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infection. Ceftriaxone can be dosed once daily and is less expensive for outpatient therapy than oxacillin. We compared patient outcomes of MSSA osteoarticular infections treated with ceftriaxone versus oxacillin.

Methods. We conducted a retrospective cohort study of patients with MSSA osteoarticular infections at a tertiary care hospital from January 2005 to April 2010. We collected demographic, clinical, and outcome data including treatment-related adverse events. Successful treatment (clinical improvement; improved follow-up markers and imaging; no readmission for treatment) was compared at 3–6 months and >6 months after completion of intravenous antibiotics.

Results. In total, 124 patients had an MSSA osteoarticular infection; 64 (52%) had orthopedic hardware involvement. Of those patients, 74 (60%) received ceftriaxone and 50 (40%) received oxacillin. Oxacillin was more often discontinued due to toxicity (9 of 50 [18%] oxacillin vs 3 of 74 [4%] ceftriaxone; P = .01). At 3–6 and >6 months, data for 97 and 88 patients, respectively, were available for analysis. Treatment success was similar at 3–6 months (50 of 60 [83%] ceftriaxone vs 32 of 37 [86%] oxacillin; P = .7) and >6 months (43 of 56 [77%] ceftriaxone vs 26 of 32 [81%] oxacillin; P = .6). After intravenous antibiotics, 56 (45%) patients received long-term suppression with oral antibiotics (31 of 74 [42%] ceftriaxone vs 25 of 50 [50%] oxacillin; P = .4).

Conclusions. In this comparison of ceftriaxone versus oxacillin for MSSA osteoarticular infections, there was no difference in treatment success at 3–6 and >6 months following the completion of intravenous antibiotics. Patients receiving oxacillin were more likely to have it discontinued due to toxicity.

Methicillin-resistant Staphylococcus aureus (MRSA) CC22 isolates with reduced vancomycin susceptibility and an increased association with endocarditis have emerged on a background of population vancomycin minimum inhibitory concentration creep and a successful MRSA control program.

Introduction. Antimicrobial resistance and bacterial virulence factors may increase the risk of hematogenous complications during methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). This study reports on the impact of increasing vancomycin minimum inhibitory concentrations (V-MICs) and MRSA clone type on risk of hematogenous complications from MRSA BSI during implementation of an effective MRSA control program.

Methods. In sum, spa typing, staphylococcal cassette chromosome mec allotyping, and vancomycin and teicoplanin MICs were performed on 821 consecutive MRSA bloodstream isolates from 1999 to 2009. Prospectively collected data, including focus of infection, were available for 695 clinically significant cases. Logistic and multinomial logistic regression was used to determine the association between clone type, vancomycin MIC (V-MIC), and focus of infection.

Results. MRSA BSIs decreased by ∼90% during the 11 years. Typing placed isolates into 3 clonal complex (CC) groups that had different population median V-MICs (CC30, 0.5 μg/mL [n = 349]; CC22, 0.75 μg/mL [n = 272]; non-CC22/30, 1.5 μg/mL [n = 199]). There was a progressive increase in the proportion of isolates with a V-MIC above baseline median in each clonal group and a disproportionate fall in the clone group with lowest median V-MIC (CC30). In contrast, there were no increases in teicoplanin MICs. High V-MIC CC22 isolates (1.5–2 μg/mL) were strongly associated with endocarditis (odds ratio, 12; 95% confidence interval, 3.72–38.9) and with a septic metastasis after catheter-related BSI (odds ratio, 106; 95% confidence interval, 12.6–883) compared with other clone type/V-MIC combinations.

Conclusions. An interaction between clone type and V-MIC can influence the risk of endocarditis associated with MRSA BSI, implying involvement of both therapeutic and host-pathogen factors.

Liver abscesses in chronic granulomatous disease (CGD) are typically difficult to treat and often require surgery. We describe 9 X-linked CGD patients with staphylococcal liver abscesses refractory to conventional therapy successfully treated with corticosteroids and antibiotics. Corticosteroids may have a role in treatment of Staphylococcus aureus liver abscesses in CGD.

We followed antiretroviral-untreated HIV-infected adults in West Africa. In the ≥650, 500–649, 350–499, and 200–349 cells/μL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, and 10.4 per 100 person-years, respectively. Tuberculosis and visceral bacterial diseases were the most frequent events.

Background. In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count–specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)–infected adults with high CD4 cell counts. In sub–Saharan Africa, these CD4 cell count–specific estimates are scarce.

Methods. From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d’Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/μL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count–specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum.

Results. Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500–649, 350–499, 200–349, 100–199, 50–99, and 0–49 cells/μL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/μL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200–349 and ≥650 cells/μL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY).

Conclusions. Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/μL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub–Saharan Africa.

We assessed the role of genetic variation in cytokine and cytokine receptor genes in susceptibility and severity of bloodstream infections with Candida species, which revealed a major role for functional polymorphisms in interleukin-10 and interleukin-12p40 in predisposing to persistent fungemia.

Background. Candida bloodstream infections cause significant morbidity and mortality among hospitalized patients. Although clinical and microbiological factors affecting prognosis have been identified, the impact of genetic variation in the innate immune responses mediated by cytokines on outcomes of infection remains to be studied.

Methods. A cohort of 338 candidemia patients and 351 noninfected controls were genotyped for single-nucleotide polymorphisms (SNPs) in 6 cytokine genes (IFNG, IL10, IL12B, IL18, IL1β, IL8) and 1 cytokine receptor gene (IL12RB1). The association of SNPs with both candidemia susceptibility and outcome were assessed. Concentrations of pro- and antiinflammatory cytokines were measured in in vitro peripheral blood mononuclear cell stimulation assays and in serum from infected patients.

Results. None of the cytokine SNPs studied were associated with susceptibility to candidemia. Persistent fungemia occurred in 13% of cases. In the multivariable model, persistent candidemia was significantly associated with (odds ratio [95% confidence interval]): total parenteral nutrition (2.79 [1.26–6.17]), dialysis dependence (3.76 [1.46–8.64]), and the SNPs IL10 rs1800896 (3.45 [1.33–8.93]) and IL12B rs41292470 (5.36 [1.51–19.0]). In vitro production capacity of interleukin-10 and interferon-γ was influenced by these polymorphisms, and significantly lower proinflammatory cytokine concentrations were measured in serum from patients with persistent fungemia.

Conclusions. Polymorphisms in IL10 and IL12B that result in low production of proinflammatory cytokines are associated with persistent fungemia in candidemia patients. This provides insights for future targeted management strategies for patients with Candida bloodstream infections.

High attack rates and the ability of Staphylococcus aureus to develop resistance to all antibiotics in medical practice heightens the urgency for vaccine development. S. aureus causes many disease syndromes, including invasive disease, pneumonia, and skin and soft tissue infections. It remains unclear whether a single vaccine could protect against all of these. Vaccine composition is also challenging. Active immunization with conjugated types 5 and 8 capsular polysaccharides, an iron scavenging protein, isdB, and passive immunization against clumping factor A and lipoteichoic acid have all proven unsuccessful in clinical trials. Many experts advocate an approach using multiple antigens and have suggested that the right combination of antigens has not yet been identified. Others advocate that a successful vaccine will require antigens that work by multiple immunologic mechanisms. Targeting staphylococcal protein A and stimulating the T-helper 17 lymphocyte pathway have each received recent attention as alternative approaches to vaccination in addition to the more traditional identification of opsonophagocytic antibodies. Many questions remain as to how to successfully formulate a successful vaccine and to whom it should be deployed.

City-level Google Flu Trends, a novel Internet-based influenza surveillance tool, shows strong correlation with influenza cases, emergency department influenzalike illness visits, and several emergency department crowding measures, validating its use as an emergency department surveillance tool.

Background. Google Flu Trends (GFT) is a novel Internet-based influenza surveillance system that uses search engine query data to estimate influenza activity and is available in near real time. This study assesses the temporal correlation of city GFT data to cases of influenza and standard crowding indices from an inner-city emergency department (ED).

Methods. This study was performed during a 21-month period (from January 2009 through October 2010) at an urban academic hospital with physically and administratively separate adult and pediatric EDs. We collected weekly data from GFT for Baltimore, Maryland; ED Centers for Disease Control and Prevention–reported standardized influenzalike illness (ILI) data; laboratory-confirmed influenza data; and ED crowding indices (patient volume, number of patients who left without being seen, waiting room time, and length of stay for admitted and discharged patients). Pediatric and adult data were analyzed separately using cross-correlation with GFT.

Results. GFT correlated with both number of positive influenza test results (adult ED, r = 0.876; pediatric ED, r = 0.718) and number of ED patients presenting with ILI (adult ED, r = 0.885; pediatric ED, r = 0.652). Pediatric but not adult crowding measures, such as total ED volume (r = 0.649) and leaving without being seen (r = 0.641), also had good correlation with GFT. Adult crowding measures for low-acuity patients, such as waiting room time (r = 0.421) and length of stay for discharged patients (r = 0.548), had moderate correlation with GFT.

Conclusions. City-level GFT shows strong correlation with influenza cases and ED ILI visits, validating its use as an ED surveillance tool. GFT correlated with several pediatric ED crowding measures and those for low-acuity adult patients.

Mucormycosis has emerged as an important opportunistic infection, especially in severely immunosuppressed hosts. The evolving epidemiology, immunopathogenesis, molecular virulence studies, early diagnosis, and pitfalls in designing clinical studies of mucormycosis are discussed in this article.

Clinical decision making often relies on observational data analyses. Attention to 7 readily understood statistical factors will assist in understanding observational studies. Responsible public access to de-identified source data, if feasible, is recommended to assess methodological limitations.

Clinical decisions are ideally based on randomized trials but must often rely on observational data analyses, which are less straightforward and more influenced by methodology. The authors, from a series of expert roundtables convened by the Forum for Collaborative HIV Research on the use of observational studies to assess cardiovascular disease risk in human immunodeficiency virus infection, recommend that clinicians who review or interpret epidemiological publications consider 7 key statistical issues: (1) clear explanation of confounding and adjustment; (2) handling and impact of missing data; (3) consistency and clinical relevance of outcome measurements and covariate risk factors; (4) multivariate modeling techniques including time-dependent variables; (5) how multiple testing is addressed; (6) distinction between statistical and clinical significance; and (7) need for confirmation from independent databases. Recommendations to permit better understanding of potential methodological limitations include both responsible public access to de-identified source data, where permitted, and exploration of novel statistical methods.

Mucormycosis has emerged as an important opportunistic infection, especially in severely immunosuppressed hosts. The evolving epidemiology, immunopathogenesis, molecular virulence studies, early diagnosis, and pitfalls in designing clinical studies of mucormycosis are discussed in this article.

In adults receiving buprenorphine-naloxone maintenance, buprenorphine pharmacokinetics were not changed significantly by 15-day coadministration of darunavir-ritonavir or fosamprenavir-ritonavir. The pharmacokinetics of the protease inhibitors did not differ from those in matched controls receiving only the protease inhibitors.

Background. This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir.

Methods. The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opioid-dependent, buprenorphine-naloxone–maintained, human immunodeficiency virus (HIV)–negative volunteers (11 for darunavir-ritonavir and 10 for fosamprenavir-ritonavir) before and after 15 days of PI administration. PI pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and an equal number of sex-, age-, race-, and weight-matched, healthy, non–opioid-dependent volunteers who received darunavir-ritonavir or fosamprenavir-ritonavir but not buprenorphine.

Results. There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine.

Conclusions. Dose adjustments are not likely to be necessary when buprenorphine and darunavir-ritonavir or fosamprenavir-ritonavir are coadministered for the treatment of opioid dependence and HIV disease.

Extremely low birth weight (ELBW) infants with candiduria are at substantial risk for death or neurodevelopmental impairment. Therefore, identification of candiduria should prompt a systemic evaluation for disseminated Candida infection and initiation of treatment in all ELBW infants.

Background. Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW; <1000 g). We sought to determine the impact of candiduria in ELBW preterm infants.

Methods. Our study was a secondary analysis of the Neonatal Research Network study Early Diagnosis of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant Development examinations at 18–22 months of corrected age. Risk factors were compared between groups using exact tests and general linear modeling. Death, NDI, and death or NDI were compared using generalized linear mixed modeling.

Results. Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2 of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515 [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive urine culture result first. Most urine isolates were Candida albicans (21 of 34 [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater among those with candiduria (50%) than among those with suspected but not proven infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2–5.3]) after adjustment. No difference in death and death or NDI was noted between infants with candiduria and those with candidemia.

Conclusions. These findings provide compelling evidence that ELBW infants with candiduria are at substantial risk of death or NDI. Candiduria in ELBW preterm infants should prompt a systemic evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida infection and warrants treatment.

Paradoxical immune reconstitution inflammatory syndrome (IRIS) was uncommon in patients with AIDS-defining Candida esophagitis or Pneumocystis pneumonia, whereas over 10% of those with Kaposi sarcoma (KS), tuberculosis, or Cryptococcus experienced this syndrome. Visceral KS-IRIS led to considerable morbidity and mortality.

Background. The incidence of immune reconstitution inflammatory syndrome (IRIS) when antiretroviral therapy (ART) is initiated after an AIDS-defining opportunistic infection (OI) is uncertain and understudied for the most common OIs.

Methods. We examined patients in the University of Washington Human Immunodeficiency Virus Cohort initiating potent ART subsequent to an AIDS-defining OI. IRIS was determined through retrospective medical record review and adjudication using a standardized data collection process and clinical case definition. We compared demographic and clinical characteristics, and immunologic changes in patients with and without IRIS.

Results. Among 196 patients with 260 OIs, 21 (11%; 95% confidence interval, 7%–16%) developed paradoxical IRIS in the first year on ART. The 3 most common OIs among study patients were Pneumocystis pneumonia (PCP, 28%), Candida esophagitis (23%), and Kaposi sarcoma (KS, 16%). Cumulative 1-year incidence of IRIS was 29% (12/41) for KS, 16% (4/25) for tuberculosis, 14% (1/7) for Cryptococcus, 10% (1/10) for Mycobacterium avium complex, and 4% (3/72) for PCP. Morbidity and mortality were highest in those with visceral KS-IRIS compared with other types of IRIS (100% [6/6] vs 7% [1/15], P < .01). Patients with mucocutaneous KS and tuberculosis-IRIS experienced greater median increase in CD4+ cell count during the first 6 months of ART compared with those without IRIS (+158 vs +53 cells/μL, P = .04, mucocutaneous KS; +261 vs +113, P = .04, tuberculosis).

Conclusions. Cumulative incidence and features of IRIS varied depending on the OI. IRIS occurred in >10% of patients with KS, tuberculosis, or Cryptococcus. Visceral KS-IRIS led to considerable morbidity and mortality.