Potent Combination Antiretroviral Therapy Research Articles

Cesarean delivery and risk of HIV vertical transmission in Southern Brazil, 2008-2018

Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.

Patterns of pregnancy loss among women living with and without HIV in Brazil, 2008–2018

Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination antiretroviral therapy. We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil. Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach. A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P=.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P<.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P=.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P=.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77-1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88-1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23-2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11-1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77-4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80-1.04). In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil.

Towards a Functional Cure of HIV-1: Insight Into the Chromatin Landscape of the Provirus.

Despite potent combination antiretroviral therapy, HIV-1 infection persists due to irreversible integration of the virus in long-living cells of the immune system. The main focus of HIV-1 cure strategies has been on HIV-1 eradication, yet without great success so far. Therefore, HIV-1 remission or a functional cure, whereby the virus is silenced rather than eradicated, is considered as an alternative strategy. Elite controllers, individuals who spontaneously control HIV-1, may point us the way toward a functional HIV-1 cure. In order to achieve such a cure, a profound understanding of the mechanisms controlling HIV-1 expression and silencing is needed. In recent years, evidence has grown that the site of integration as well as the chromatin landscape surrounding the integration site affects the transcriptional state of the provirus. Still, at present, the impact of integration site selection on the establishment and maintenance of the HIV-1 reservoirs remains poorly understood. The discovery of LEDGF/p75 as a binding partner of HIV-1 integrase has led to a better understanding of integration site selection. LEDGF/p75 is one of the important determinants of integration site selection and targets integration toward active genes. In this review, we will provide an overview of the most important determinants of integration site selection. Secondly, we will discuss the chromatin landscape at the integration site and its implications on HIV-1 gene expression and silencing. Finally, we will discuss how interventions that affect integration site selection or modifications of the chromatin could yield a functional cure of HIV-1 infection.

Recrudescence of Natural Coccidioidomycosis During Combination Antiretroviral Therapy in a Pigtail Macaque Experimentally Infected with Simian Immunodeficiency Virus.

Coccidioidomycosis is a common fungal infection in people living with HIV-1, particularly in southwest regions of the United States where the Coccidioides sp. is endemic, but rates of infection have significantly declined in the era of potent combination antiretroviral therapy (cART). Natural coccidioidomycosis also occurs in outdoor-housed macaques residing in the southwestern states that are utilized in biomedical research. Here, we report on a recrudescent case of previously treated, naturally occurring coccidioidomycosis in a pigtail macaque that was experimentally infected with simian immunodeficiency virus (SIV) and virally suppressed on cART. Coccidioides IgG antibody titer became detectable before discontinuation of cART, but symptomatic coccidioidomycosis developed subsequent to cART withdrawal. This animal was screened and treated in accordance with the guidelines for the prevention and treatment of coccidioidomycosis, suggesting that macaques with a history of coccidioidomycosis should be excluded from enrollment in HIV studies. Continual monitoring for known endemic pathogens based on the colony of origin is also recommended for animals utilized for HIV/AIDS research.

Kaposi’s Sarcoma in the Era of ART: A Single Institutional Retrospective Review

Background: Kaposi’s Sarcoma (KS) is an angioproliferative tumor characterized by 4 sub-types: classic (CKS), endemic, immunosuppression related, and epidemic (AIDS-KS). AIDS-KS prevalence has decreased since the introduction of potent combination anti-retroviral therapy (ART). Even so, KS lesions develop in patients with undetectable viral loads and high CD4 counts. KS is variable across its subtypes, disease course, and clinical outcomes. Treatment must therefore be individualized. Results: 130 patients with a diagnosis of KS were identified, of which 95 (73.1%) had AIDS-KS and 31 (23.8%) had CKS. There were 4 patients with immunosuppression therapy-related KS and no endemic cases. 18.9% of AIDS-KS patients had metastatic disease vs. 6.5% in the CKS group. At KS diagnosis, 50.5% of AIDS-KS patients had CD4 count &gt;200 cells/mm3 and 33.7% had HIV viral load level &lt;=20 copies/mL. Among the 53 patients who received chemotherapy, 45 were AIDS-KS patients (84.9%). The most commonly used chemotherapy was doxorubicin hydrochloride liposomal injection (78.4%) with an average of 10 cycles. Other chemotherapy utilized includes paclitaxel and interferon. 16 pts (12.3%) died, of which only two died of disseminated AIDS-KS. Conclusions: Our retrospective study confirms that 75% of pts diagnosed with KS have AIDS-KS. Despite introduction of ART and the well-controlled nature HIV/AIDS, KS continues to occur. AIDS-KS patients are younger, more likely to have metastatic disease and more frequently treated with chemotherapy. Poorly controlled HIV confers a worse outcome in AIDS-KS. Further investigations are required to better understand the etiology of AIDS-KS in pts with undetectable HIV viral loads and immune recovery.

Considerations on nosology for HIV-associated neurocognitive disorders: it is time to update?

The prognosis and the clinical manifestations of HIV infection have changed with the introduction of the potent combination antiretroviral therapy (cART); however, up to 50% of patients meet research criteria for "HIV-associated neurocognitive disorders" (HAND) according with current nosology. The majority of patients affected by HAND, especially in cohorts with suppressed plasma viremia, showed an Asymptomatic Neurocognitive Impairment (ANI), without any functional impairment. After more than 10years from the introduction of the current so-called "Frascati criteria", this mini-review aimed to address the emerging limitations in current diagnosis procedures. We discussed the most relevant literature on HAND prevalence, etiology, and diagnosis. We addressed three main emerging issues: (1) the unclear clinical relevance of ANI entity; (2) the evidences that Frascati criteria could produce a significant overestimation of HAND; (3) the need to better identify patients with a higher risk to develop HAND requiring routine neuropsychological examinations. Frascati criteria should be updated to better respond to the present characteristics of HIV + cohorts and to help clinicians in their cognitive and global management.

Kaposi Sarcoma of the Gastrointestinal Tract in the Era of Combination Anti-Retro Viral Therapy

AIDS related Kaposi sarcoma (KS) is the most common tumor identified in HIV patients. Classically presents as cutaneous vascular endothelial tumors associated with HHV-8 infection. Visceral manifestation in the absence of cutaneous manifestation is uncommon. The annual incidence of Kaposi sarcoma in the United States has been steadily declining with the advent of highly potent combination anti-retroviral therapy (ART). We present an unfortunate case of a HIV positive male with extensive gastrointestinal Kaposi sarcoma. 50 year old male with prior diagnosis of HIV, non-compliant with ART presented with weight loss, abdominal pain, distention, vomiting and diarrhea for 3 months. Examination revealed a cachectic appearing male, moderate abdominal distention with mild diffuse tenderness throughout the abdomen. No cutaneous lesions identified on examination. Blood work significant for anemia, leukopenia, elevated HIV viral load >210,000 with a low CD4 count of 100. Stool studies for ova and parasites were negative. CT imaging revealed long segment mural thickening extending from the terminal ileum, descending colon to the rectum with multiple dilated fluid filled loops of small bowel with scattered large to small extensive mesenteric lymphadenopathy. EGD revealed multiple raised red to purplish nodular lesions in the oropharynx, esophagus, stomach and duodenum. Similar lesions were found on colonoscopy throughout the colon and terminal ileum associated with significant edema and narrowing in the region of the terminal ileum and sigmoid colon (Image 1). Biopsy from various sites revealed spindle cell proliferation with extravasation of red blood cells (Image2). Immunostain positive for HHV-8 consistent with the diagnosis of Kaposi's sarcoma (Image3). Patient improved on ART and was later discharged home with plans for outpatient chemotherapy. Significant advancements in the field of ART has led to a decrease in the prevalence of Kaposi sarcoma in the 21st century. Incidence of KS has shown a significant decline in United states from 47 cases per 1 million people in the 1990 to 6 cases per 1 million people because of highly effective treatments available for HIV/AIDS. Gastrointestinal manifestations commonly reported are abdominal pain, malabsorption, bleeding and rarely obstruction. GI manifestation can be easily missed in the absence of cutaneous manifestation, hence a high degree of suspicion can lead to early diagnosis and improved outcomes.2984_A Figure 1. Colonoscopy images showing multiple raised red to purple nodules throughout the colon2984_B Figure 2. H&E stain of the duodenal mucosa showing scattered bland spindle cell proliferation with extravasated red blood cells.2984_C Figure 3. Immunostain positive for HHV -8

The Molecular Basis for Human Immunodeficiency Virus Latency.

Although potent combination antiretroviral therapy can effectively block viral replication in the host, human immunodeficiency virus (HIV) persists due to the existence of latent but replication-competent proviruses residing primarily in a very small population of resting memory CD4+ T cells. Viral latency is established when the expression of the autoregulatory viral trans-activating factor Tat is reduced to subthreshold levels. The absence of Tat reduces HIV transcription and protein production to levels that make the host cell invisible to the immune system and refractory to antiretroviral treatment. Key host cell mechanisms that drive HIV into latency are sequestration of transcription initiation factors, establishment of epigenetic barriers inactivating the proviral promoter, and blockage of the assembly of the host elongation factor P-TEFb. This comprehensive understanding of the molecular control of HIV transcription is leading to the development of optimized combinatorial reactivation and immune surveillance strategies designed to purge the latent viral reservoir.

Underutilization of aspirin in people living with human immunodeficiency virus at increased risk for acute myocardial infarction: Systematic review and meta-analysis

Context: With the increased availability of potent combination antiretroviral therapies, the life expectancy of people living with human immunodeficiency virus (PLHIV) has greatly increased. This rapid improvement in lifespan has served as a catalyst for a paradigm shift in human immunodeficiency virus (HIV) care. The focus of HIV care models has transitioned from the sole treatment of acute opportunistic infections to comprehensive management of chronic diseases, such as cardiovascular disease (CVD). Multiple studies have demonstrated that PLHIV are 50% more likely to develop acute myocardial infarction (AMI), compared to the general population. Cardiovascular risk prevention is becoming an essential component of the overarching HIV treatment plan. Aims: This meta-analysis aims to compare the rate of aspirin use for AMI prevention in indicated patients between PLHIV and general population. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, and MEDLINE databases were used to identify observational cohort trials. Studies were assessed by two reviewers for inclusion criteria. Two separate random-effects meta-analyses' models were performed using the DerSimonian and Laird method. Heterogeneity was assessed using the I2 value. Meta-regression with study level variables was used to explore potential sources of heterogeneity. The funnel-plot-based trim-and-fill method was applied to detect and adjust for potential publication bias. Statistical tests were two-sided and P< 0.05 was considered statistically significant. Results: A total of 13 studies were included for analysis. In these trials, 30.4% of PLHIV with increased risk for coronary heart disease (CHD) used aspirin for AMI prevention, compared to 36.9% of patients at risk of CHD in the general population. Conclusions: The results of this meta-analysis provide evidence that aspirin is underutilized in both PLHIV and the general population across broad geographical zones. Aspirin use was found to be markedly lower in PLHIV compared to the general population. This is the first study to pool results from regional studies to assess disparities in aspirin use for AMI prevention between PLHIV and the general population across broad geographical zones.

HIV Infection and Myocardial Infarction.

After the advent of the potent combination antiretroviral therapy (cART) the incidence of acquired immune deficiency syndrome (AIDS) has declined dramatically and HIV infection became a chronic disease with a significant increase in the life expectancy of HIV-positive people. Consequently, chronic comorbidities as coronary heart disease raised an increasing concern in this population. Aim of this editorial article is to review the most recent data about the cardiovascular disease risk among HIV-positive persons and to suggest an appropriate clinical management. An increased risk of myocardial infarction has been reported among HIVinfected subjects compared to the general population, but the pathogenic mechanism of this accelerated atherosclerotic process is complex and certainly multifactorial. The occurrence of myocardial infarction may be the consequence of traditional risk factors (that are overrepresented in the HIVinfected population), direct viral replication, and long-term toxicity of the antiretroviral drugs. Moreover, despite the persistent viral suppression induced by cART usually reduces the cardiovascular risk, several studies show in HIV-positive subjects a condition of chronic inflammation and immune activation that could lead to both accelerated endothelial dysfunction and atherosclerotic disease. The cardiovascular risk reduction and coronary heart disease prevention are today a leading challenge for all the clinicians involved in the HIV patients' care.

Treating HIV disease: back to the patient?

HIV disease has dramatically changed in the last two decades from a progressive, lethal disease to a chronic manageable condition. These changes are due to the availability of potent antiretroviral combination therapy, which also have the potential to contribute significantly to the control of the epidemic. Among persons living with HIV, incidence of immunosuppression-related opportunistic illnesses has clearly decreased, while an increase was observed in the prevalence of age-related noncommunicable comorbidities, including cardiovascular, metabolic, renal, bone and hepatic disease, due to chronic inflammatory state and to an overall aging of the population of persons with HIV. It has been predicted that by 2030 more than 80% of older persons with HIV will have at least one comorbidity, compared to 19% of non HIV-infected persons, and that one fourth of these persons will have three or more comorbidities. Among persons with HIV, the prevalence of frailty is increasing. Choice of therapeutic approach to HIV disease should take into account, in addition to the ability of drug combination to suppress viral replication, the potential for long term adherence to treatment, the lack of long term toxicity, the possibility to fully restore immune function and prevent immune activation, thus reducing the risk of chronic inflammation related disease. In addition the overall impact of treatment on patients' well-being must be considered, and patients related outcomes should be used to measure this impact.

Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients.

The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents.

End-Stage Renal Disease and HIV: Where We Are Now

Although the incidence of HIV-associated nephropathy has declined since the advent of potent combination antiretroviral therapy (ART), HIV-infected

The Looming Surge in Costs of HIV Care for Older Patients

The use of potent combination antiretroviral therapy (ART) has resulted in improved long-term survival of people with HIV infection and an ongoing

Differentiating HIV-associated nephropathy from antiretroviral drug-induced nephropathy: a clinical challenge.

With the introduction of potent combination antiretroviral therapy (cART) into clinical practice, HIV-infected patients have garnered much benefit. However, kidney disease continues to be a potential complication in this group. Whereas HIV-associated nephropathy (HIVAN) was the major renal complication prior to cART, co-morbid diseases and adverse renal effects of various drugs, in particular cART, now complicate the landscape. Clinicians now must differentiate HIVAN from cART nephrotoxicity. While sometimes this is easy and relatively straightforward, often the clinician faces a difficult challenge distinguishing these two etiologies of kidney disease. This review will discuss HIVAN and cART-related kidney disease and review the clinical and laboratory data that may be useful in differentiating these processes. Often, however, kidney biopsy may be required to differentiate HIVAN from cART nephrotoxicity as well as other kidney lesions associated with concurrent co-morbidities, both infectious and non-infectious.

HIV-1 Specific Antibody Titers and Neutralization among Chronically Infected Patients on Long-Term Suppressive Antiretroviral Therapy (ART): A Cross-Sectional Study

The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER) in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA <50 copies/mL for ≤5 years. 22% of patients neutralized a HIV-1 primary isolate (HIV-1JR-FL) and 8% neutralized a HIV-2/HIV-1 MPER chimera. Significantly greater HIV-1JR-FL neutralization was found among patients with >10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤10 years, p = 0.02) and a trend toward greater neutralization in patients with ≤5 years of HIV RNA <50 copies/mL (7/20 [35.0%] versus 4/31 [12.9%] for >5 years, p = 0.08). All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.

Timing, Adherence, Resistance, and ... Persistence? New Insight Into the Mechanisms of Failure of HIV Type 1 Postexposure Prophylaxis

Timing, Adherence, Resistance, and ... Persistence? New Insight Into the Mechanisms of Failure of HIV Type 1 Postexposure Prophylaxis

HIV-Associated Neurocognitive Disorders: Perspective on Management Strategies

Potent combination antiretroviral therapy (ART) has resulted in dramatic improvements in AIDS-associated morbidity and mortality. Although combination ART has resulted in a significant reduction in HIV-associated dementia, the most severe of the HIV-associated neurocognitive disorders (HAND), the overall prevalence of HAND among this population is estimated at 40%. It has been recognized that the central nervous system (CNS) serves as a reservoir for HIV, and neuronal damage begins at the time of acute infection and persists due to chronic infection of microglial and perivascular macrophages. Although combination ART has resulted in virologic control in the plasma compartment, virologic breakthrough can potentially ensue within the CNS compartment due to limited ART drug exposure. The purpose of this review is to discuss the definition, clinical spectrum, and risk factors associated with HAND, review the pathogenesis of HAND, and address the pharmacologic challenges associated with ART drug exposure in the CNS compartment.

Survival Improvement with ART — Not Only for the Developed World

The use of potent combination antiretroviral therapy (ART) has dramatically reduced the morbidity and mortality associated with HIV infection. In the

Predictors of Mortality and Differences in Clinical Features among Patients with Cryptococcosis According to Immune Status

IntroductionCryptococcosis is an invasive fungal infection causing substantial morbidity and mortality. Prognostic factors are largely derived from trials conducted prior to the modern era of antifungal and potent combination antiretroviral therapies, immunosuppression, and transplantation. Data describing the clinical features and predictors of mortality in a modern cohort are needed.MethodsWe conducted a retrospective cohort study of patients at our institution diagnosed with cryptococcosis from 1996 through 2010. Data included demographics, clinical features, diagnostics, treatment, and outcomes.ResultsWe identified 302 individuals: 108 (36%) human immunodeficiency virus (HIV)-positive, 84 (28%) organ transplant recipients (OTRs), and 110 (36%) non-HIV, non-transplant (NHNT) patients including 39 with no identifiable immunodeficiency. Mean age was 49 years, 203 (67%) were male and 170 (56%) were white. All-cause mortality at 90 days was 21%. In multivariable logistic regression analyses, cryptococcemia (OR 5.09, 95% CI 2.54–10.22) and baseline opening pressure >25 cmH2O (OR 2.93, 95% CI 1.25–6.88) were associated with increased odds of mortality; HIV-positive patients (OR 0.46, 95% CI 0.19–1.16) and OTRs (OR 0.46, 95% CI 0.21–1.05) had lower odds of death compared to NHNT patients.ConclusionsPredictors of mortality from cryptococcosis in the modern period include cryptococcemia, high intracranial pressure, and NHNT status while drug(s) used for induction and historical prognostic factors including organ failure syndromes and hematologic malignancy were not associated with mortality.