Dataset Information

High prevalence of gastrointestinal manifestations among Cytomegalovirus end-organ disease in the combination antiretroviral era.

ABSTRACT:

Background

Cytomegalovirus (CMV) end-organ disease (EOD) continues to pose a significant risk to patients with advanced HIV disease despite decreased incidence with combination anti-retroviral therapy (ART) and lower mortality with effective anti-CMV therapy. Subclinical CMV shedding may also contribute to ongoing inflammation and non-infectious comorbidities.

Methods

We examined the occurrence of CMV EOD and CMV shedding in a cohort of patients participating in a prospective observational study of severely immunosuppressed (CD4 ≤100 cells/μl), ART-naïve, HIV-1 infected adult participants.

Results

We studied 206 participants, of whom 193 (93.7%) were CMV IgG positive. Twenty-five participants (12.1%) developed confirmed CMV EOD. At baseline, 47 (22.8%) had CMV viremia detectable by PCR in the absence of clinical disease (CMV viremia). The remaining 134 (65%) had neither CMV EOD nor CMV viremia detected at baseline. Five participants with CMV EOD (2.4% of total cohort, 20% of CMV EOD) met AIDS Clinical Trials Group criteria for CMV immune reconstitution inflammatory syndrome (IRIS). Only one-third of CMV EOD patients had retinitis, while two-thirds presented with histologically confirmed gastrointestinal illness. CMV viremia was associated with higher percentages of activated CD8⁺ T cells even after HIV suppression.

Conclusion

The manifestations of CMV EOD in advanced HIV disease before and after initiation of ART may be more diverse than previously described, with high incidence of gastrointestinal illness. Recognition and treatment of unusual clinical presentations of CMV infection remains important in reducing morbidity and mortality from HIV co-infections.

SUBMITTER: Caplan MR

PROVIDER: S-EPMC8446803 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:It is estimated that 650,000 patients may develop human immunodeficiency virus (HIV)-related renal disease in South Africa. South Africa has recently adopted WHO policy, stipulating that all HIV-infected patients have access to antiretroviral treatment (ART) irrespective of CD4 cell count.We searched Google Scholar, PubMed, Medline, Cochrane Library, Worldcat.org and EBSCO host databases from July 2015 to December 2015. Eligibility criteria included articles pertaining to renal manifestations of HIV in South Africa from 2004 to 2015 in adult patients (≥ 18 years). We independently reviewed the articles for quality. Thematic content analysis was performed to identify patterns of renal manifestations from the included studies. The risk of bias (e.g. internal validity) in the included studies was evaluated using the mixed methods appraisal tool.Eleven out 21 studies were eligible for data extraction. The prevalence of urine abnormalities on urine dipsticks was high but had poor sensitivity and specificity for detecting renal impairment. Normal renal function occurred in 28.4 to 79% of patients, mild renal impairment occurred in 19 to 57.1% and moderate renal impairment in 2 to 14.4%. Severe renal impairment occurred in 1.3% of patients. Both the Cockcroft-Gault equation (after correcting for bias) and the 4-variable Modification of Diet in Renal Disease equation (without the ethnicity factor for African Americans) have been validated for the estimation of glomerular filtration rate (eGFR) in Black South Africans. HIV-associated nephropathy was the most prevalent histology seen (57.2%). Older age, a lower CD4 count, a low haemoglobin and a detectable viral load were associated with renal impairment. Renal function improved in the first year of commencing ART as evidenced by the regression of proteinuria and the increase in eGFR.The findings of the review have implications to the recently adopted 'test and treat' approach to HIV prevention and management.PROSPERO CRD42016039270.

Project description:IntroductionDiarrhea poses a substantial burden for patients with human immunodeficiency virus (HIV), negatively impacting quality-of-life (QoL) and adherence to antiretroviral therapy. During the combination antiretroviral therapy (cART) era, as incidence of opportunistic infection as a cause of diarrhea decreased, incidence of noninfectious diarrhea (including diarrhea as an adverse event [AE] of cART and HIV enteropathy) increased proportionately. A literature search was conducted for information on prevalence, etiology, and treatment options for noninfectious diarrhea in patients with HIV.ResultsFor marketed antiretroviral therapies, up to 28% of patients live with >4 loose or watery stools per day. The US Food and Drug Administration (FDA) does not require pharmaceutical manufacturers to include, within approved prescribing information, prevalence rates for all grades of diarrhea. Traditionally, noninfectious diarrhea management focused on avoiding use of diarrhea-associated cART; symptom management (nonpharmacologic and/or pharmacologic); and, as a last resort, changing cART. Examining the evidence upon which this approach is based reveals that most strategies rely upon anecdotal information and case reports. This review summarizes the literature and updates clinicians on the most recent options for management of noninfectious diarrhea in patients with HIV.ConclusionDiarrhea in patients with HIV is a significant unmet clinical need that contributes to worsening QoL and complicates medical management. Approaching management using a stepwise method of nonpharmacologic (diet), nonprescription (over-the-counter) and, finally, prescription agent changes (modification of cART or addition of an evidence-based antidiarrheal) appears reasonable, despite a lack of clear scientific evidence to support the initial two steps of this approach. If diet modifications, including psyllium and fiber introduction, fail to resolve noninfectious diarrhea in patients with HIV, loperamide followed by crofelemer should be considered. Clinicians are encouraged to review the most recent literature, not rely upon prescribing information. Continued vigilance by HIV providers to the presence of gastrointestinal AEs, even in patients taking the most recently approved antiretroviral agents, is warranted. Additional research is justified in identifying the etiology and management of HIV-associated diarrhea in patients on successful cART regimens.