HIV-1 Viral Load Assays for Resource-Limited Settings

Fiscus, Susan A.; Cheng, Ben; Crowe, Suzanne; Demeter, Lisa M.; Jennings, Cheryl; Miller, Veronica; Respess, Richard; Stevens, Wendy

doi:10.1371/journal.pmed.0030417

Cited by 143 publications

(137 citation statements)

References 83 publications

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“…35,[47][48][49] The amount of p24 released has been used as a marker for virus maturation. 40,41 Our result suggests that CSN5 may be a rate-limiting factor for HIV release. One possible mechanism underlying this phenomenon would be that COP9-associated CSN5 deubiquitination activity controls Gag ubiquitination.…”

Section: Discussionmentioning

confidence: 70%

COP9-Associated CSN5 Regulates Exosomal Protein Deubiquitination and Sorting

Liu

Shah

Xiang

et al. 2009

The American Journal of Pathology

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Ubiquitinated endosomal proteins that are deposited into the lumens of multivesicular bodies are either sorted for lysosomal-mediated degradation or secreted as exosomes into the extracellular milieu. The mechanisms that underlie the sorting of cellular cargo proteins are currently unknown. In this study, we show that the COP9 signalosome (CSN)-associated protein CSN5 quantitatively regulated proteins that were sorted into exosomes. Western blot analysis of exosomal proteins indicated that small interfering (si)RNA knockdown of CSN5 results in increased levels of both ubiquitinated and non-ubiquitinated exosomal proteins, including heat shock protein 70, in comparison with exosomes isolated from the supernatants of 293 cells transfected with scrambled siRNA. Furthermore, 293 cells transfected with JAB1/MPN/ Mov34 metalloenzyme domain-deleted CSN5 produced exosomes with higher levels of ubiquitinated heat shock protein 70, which did not affect non-ubiquitinated heat shock protein 70 levels. The loss of COP9-associated deubiquitin activity of CSN5 also led to the enhancement of HIV Gag that was sorted into exosomes as well as the promotion of HIV-1 release, suggesting that COP9-associated CSN5 regulates the sorting of a number of exosomal proteins in both a CSN5 JAB1/MPN/Mov34 metalloenzyme domain-dependent and -independent manner. We propose that COP9-associated CSN5 regulates exosomal protein sorting in both a deubiquitinating activity-dependent and -independent manner, which is contrary to the current idea of ubiquitin-dependent sorting of proteins to exosomes.

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Section: Discussionmentioning

confidence: 70%

COP9-Associated CSN5 Regulates Exosomal Protein Deubiquitination and Sorting

Liu

Shah

Xiang

et al. 2009

The American Journal of Pathology

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“…This is by far lower than the finding of another study conducted in private health facilities in Addis Ababa. This could be due to variation in the service quality including monitoring HIV Viral load is often not performed, the assays are costly and require sophisticated, expensive laboratory equipment and trained technicians private health facilities quality [18,21,22]. The incidence of immunological, virological and clinical failure in this study is 2.1, 0.24 and 0.13 per 100 person years of follow-up respectively.…”

Section: Discussionmentioning

confidence: 83%

Incidence and Predictors of Anti-Retroviral Treatment (ART) Failure among Adults Receiving HIV Care at Zewditu Memorial Hospital, Addis Ababa, Ethiopia

Sisay¹,

Bekele²,

Sisay³

et al. 2017

J AIDS Clin Res

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Background: Despite availability of antiretroviral therapy, HIV is responsible for 2.7 million new infections and 2.0 million deaths from worldwide. Anti-Retroviral treatment failure is not a commonly diagnosis in healthcare facilities in Ethiopia and there is dearth of information on the extent and predictors of treatment failure among adults receiving HIV care in the study setting. The aim of the current study is to assess the incidence and predictors of Anti-Retroviral Treatment (ART) failure among adults receiving HIV care at Zewditu Memorial Hospital, Addis Ababa, Ethiopia.Methods: Facility based retrospective cohort study design was employed on archived data from 2011 to 2016. Data compilation checklist was developed from intake card and ART follow-up card. The collected data were coded and entered using Epi Info 7 and analysed using Statistical Packages for Social Science (SPSS) version 20 software. Results:The overall incidence rate of ART treatment failure were 4.91 cases per person months follow up with 2.1, 0.24 and 0.13 immunological, clinical and virological treatment failure cases per 100 person years of follow-up respectively Conclusion:The incidence of Anti-Retroviral Treatment failure was considerable among the study participants. The predictors for ART failure were WHO stage 3 at start, CD4 count at base line, disclosure and opportunistic infections. Comprehensive interventions have to be in place to tackle treatment failure among adults on ART through rendering optimum care focusing on adults with advanced WHO stage, lower CD4 count at baseline, opportunistic infections and people who did not disclose their HIV status.

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“…This requires easy-to-use, point-of-care, monitoring tools. 2,3 Unfortunately, such tools are not available as yet and care providers have to rely on the evolution of clinical markers to assess patients. Measurement of body weight is an easy-to-implement, routinely measured parameter used for the follow-up of patients on ART in LIC.…”

Section: Introductionmentioning

confidence: 99%

Weight loss after the first year of stavudine-containing antiretroviral therapy and its association with lipoatrophy, virological failure, adherence and CD4 counts at primary health care level in Kigali, Rwanda

Griensven

Zachariah

Mugabo

et al. 2010

Transactions of the Royal Society of Tropical Medicine and Hygi

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CitationWeight loss after the first year of stavudine-containing antiretroviral therapy and its association with lipoatrophy, virological failure, adherence and CD4 counts at primary health care level in Kigali, Rwanda. 2010, 104 (12) a b s t r a c tThis study was conducted among 609 adults on stavudine-based antiretroviral treatment (ART) for at least one year at health center level in Kigali, Rwanda to (a) determine the proportion who manifest weight loss after one year of ART (b) examine the association between such weight loss and a number of variables, namely: lipoatrophy, virological failure, adherence and on-treatment CD4 count and (c) assess the validity and predictive values of weight loss to identify patients with lipoatrophy. Weight loss after the first year of ART was seen in 62% of all patients (median weight loss 3.1 kg/year). In multivariate analysis, weight loss was significantly associated with treatment-limiting lipoatrophy (adjusted effect/kg/year -2.0 kg, 95% confidence interval -0.6;-3.4 kg; P < 0.01). No significant association was found with virological failure or adherence. Higher on-treatment CD4 cell counts were protective against weight loss. Weight loss that was persistent, progressive and/or chronic was predictive of lipoatrophy, with a sensitivity and specificity of 72% and 77%, and positive and negative predictive values of 30% and 95%. In low-income countries, measuring weight is a routine clinical procedure that could be used to filter out individuals with lipoatrophy on stavudine-based ART, after alternative causes of weight loss have been ruled out.

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HIV-1 Viral Load Assays for Resource-Limited Settings

Abstract: The authors discuss studies on the low-cost viral load assays that are currently available and their potential for use in resource-limited settings.

Cited by 143 publications

References 83 publications

COP9-Associated CSN5 Regulates Exosomal Protein Deubiquitination and Sorting

COP9-Associated CSN5 Regulates Exosomal Protein Deubiquitination and Sorting

Incidence and Predictors of Anti-Retroviral Treatment (ART) Failure among Adults Receiving HIV Care at Zewditu Memorial Hospital, Addis Ababa, Ethiopia

Weight loss after the first year of stavudine-containing antiretroviral therapy and its association with lipoatrophy, virological failure, adherence and CD4 counts at primary health care level in Kigali, Rwanda

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