| 1. |
- Arimide, Dawit Assefa, et al.
(författare)
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High Level of HIV Drug Resistance and Virologic Nonsuppression among Female Sex Workers in Ethiopia : A Nationwide Cross-Sectional Study
- 2022
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - 1525-4135. ; 89:5, s. 566-574
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To determine viral load (VL) nonsuppression (VLN) rates, HIV drug resistance (HIVDR) prevalence, and associated factors among female sex workers (FSWs) in Ethiopia.Methods:A cross-sectional biobehavioral survey was conducted among FSWs in 11 cities in Ethiopia in 2014. Whole blood was collected, and HIVDR genotyping was performed. Logistic regression analysis was performed to identify factors associated with VLN and HIVDR.Results:Among 4900 participants, 1172 (23.9%) were HIV-positive and 1154 (98.5%) had a VL result. Participants were categorized into antiretroviral therapy (ART) (n = 239) and ART-naive (n = 915) groups based on self-report. From the 521 specimens (ART, 59; ART-naive, 462) with VL ≥1000 copies/mL, genotyping was successful for 420 (80.6%) and 92 (21.9%) had drug resistance mutations (DRMs). Pretreatment drug resistance (PDR) was detected in 16.5% (63/381) of the ART-naive participants. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTIs (NNRTIs), and dual-class DRMs were detected in 40 (10.5%), 55 (14.4%), and 35 (9.2%) of the participants, respectively. Among 239 participants on ART, 59 (24.7%) had VLN. Genotyping was successfully performed for 39 (66.1%). DRMs were detected in 29 (74.4%). All 29 had NNRTI, 23 (79.3%) had NRTI or dual-class DRMs. VLN was associated with age 35 years or older, CD4+T-cell count <350 cells/mm3, and being forced into selling sex. PDR and acquired drug resistance were associated with CD4+T-cell count <350 cells/mm3(P < 0.001).Conclusions:The high VLN and HIVDR rates among FSWs underscore the need for targeted interventions to improve ART access and virologic monitoring to maximize the benefit of ART and limit the spread of HIV and HIVDR.
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| 2. |
- Arimide, Dawit Assefa, et al.
(författare)
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HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Background The HIV-1 epidemic in Ethiopia has been shown to be dominated by two phylogenetically distinct subtype C clades, the Ethiopian (C'-ET) and East African (C-EA) clades, however, little is known about the temporal dynamics of the HIV epidemic with respect to subtypes and distinct clades. Moreover, there is only limited information concerning transmission of HIV-1 drug resistance (TDR) in the country. Methods A cross-sectional survey was conducted among young antiretroviral therapy (ART)-naïve individuals recently diagnosed with HIV infection, in Gondar, Ethiopia, 2011-2013 using the WHO recommended threshold survey. A total of 84 study participants with a median age of 22 years were enrolled. HIV-1 genotyping was performed and investigated for drug resistance in 67 individuals. Phylogenetic analyses were performed on all available HIV sequences obtained from Gondar (n = 301) which were used to define subtype C clades, temporal trends and local transmission clusters. Dating of transmission clusters was performed using BEAST. Result Four of 67 individuals (6.0%) carried a HIV drug resistance mutation strain, all associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). Strains of the C-EA clade were most prevalent as we found no evidence of temporal changes during this time period. However, strains of the C-SA clade, prevalent in Southern Africa, have been introduced in Ethiopia, and became more abundant during the study period. The oldest Gondar transmission clusters dated back to 1980 (C-EA), 1983 (C-SA) and 1990 (C'-ET) indicating the presence of strains of different subtype C clades at about the same time point in Gondar. Moreover, some of the larger clusters dated back to the 1980s but transmissions within clusters have been ongoing up till end of the study period. Besides being associated with more sequences and larger clusters, the C-EA clade sequences were also associated with clustering of HIVDR sequences. One cluster was associated with the G190A mutation and showed onward transmissions at high rate. Conclusion TDR was detected in 6.0% of the sequenced samples and confirmed pervious reports that the two subtype C clades, C-EA and C'-ET, are common in Ethiopia. Moreover, the findings indicated an increased diversity in the epidemic as well as differences in transmission clusters sizes of the different clades and association with resistance mutations. These findings provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.
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| 3. |
- Arimide, Dawit Assefa, et al.
(författare)
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Molecular Epidemiology and Transmission Dynamics of the HIV-1 Epidemic in Ethiopia : Epidemic Decline Coincided With Behavioral Interventions Before ART Scale-Up
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ethiopia is one of the sub-Saharan countries hit hard by the HIV epidemic. Previous studies have shown that subtype C dominates the Ethiopian HIV-1 epidemic, but the evolutionary and temporal dynamics of HIV-1 in Ethiopia have not been closely scrutinized. Understanding the evolutionary and epidemiological pattern of HIV is vital to monitor the spread, evaluate and implement HIV prevention strategies. Methods: We analyzed 1,276 Ethiopian HIV-1 subtype C polymerase (pol sequences), including 144 newly generated sequences, collected from different parts of the country from 1986 to 2017. We employed state-of-art maximum likelihood and Bayesian phylodynamic analyses to comprehensively describe the evolutionary dynamics of the HIV-1 epidemic in Ethiopia. We used Bayesian phylodynamic models to estimate the dynamics of the effective population size (Ne) and reproductive numbers (Re) through time for the HIV epidemic in Ethiopia. Results: Our analysis revealed that the Ethiopian HIV-1 epidemic originated from two independent introductions at the beginning of the 1970s and 1980s from eastern and southern African countries, respectively, followed by epidemic growth reaching its maximum in the early 1990s. We identified three large clusters with a majority of Ethiopian sequences. Phylodynamic analyses revealed that all three clusters were characterized by high transmission rates during the early epidemic, followed by a decline in HIV-1 transmissions after 1990. Re was high (4–6) during the earlier time of the epidemic but dropped significantly and remained low (Re < 1) after the mid-1990. Similarly, with an expected shift in time, the effective population size (Ne) steadily increased until the beginning of 2000, followed by a decline and stabilization until recent years. The phylodynamic analyses corroborated the modeled UNAIDS incidence and prevalence estimates. Conclusion: The rapid decline in the HIV epidemic took place a decade before introducing antiretroviral therapy in Ethiopia and coincided with early behavioral, preventive, and awareness interventions implemented in the country. Our findings highlight the importance of behavioral interventions and antiretroviral therapy scale-up to halt and maintain HIV transmissions at low levels (Re < 1). The phylodynamic analyses provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.
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| 4. |
- Belay, Mulugeta, et al.
(författare)
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Detection of Mycobacterium tuberculosis complex DNA in CD34-positive peripheral blood mononuclear cells of asymptomatic tuberculosis contacts : an observational study
- 2021
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Ingår i: The Lancet Microbe. - 2666-5247. ; 2:6, s. 267-275
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Tidskriftsartikel (refereegranskat)abstract
- Background: Haematopoietic stem cells expressing the CD34 surface marker have been posited as a niche for Mycobacterium tuberculosis complex bacilli during latent tuberculosis infection. Our aim was to determine whether M tuberculosis complex DNA is detectable in CD34-positive peripheral blood mononuclear cells (PBMCs) isolated from asymptomatic adults living in a setting with a high tuberculosis burden. Methods: We did a cross-sectional study in Ethiopia between Nov 22, 2017, and Jan 10, 2019. Digital PCR (dPCR) was used to determine whether M tuberculosis complex DNA was detectable in PBMCs isolated from 100 mL blood taken from asymptomatic adults with HIV infection or a history of recent household or occupational exposure to an index case of human or bovine tuberculosis. Participants were recruited from HIV clinics, tuberculosis clinics, and cattle farms in and around Addis Ababa. A nested prospective study was done in a subset of HIV-infected individuals to evaluate whether administration of isoniazid preventive therapy was effective in clearing M tuberculosis complex DNA from PBMCs. Follow-up was done between July 20, 2018, and Feb 13, 2019. QuantiFERON-TB Gold assays were also done on all baseline and follow-up samples. Findings: Valid dPCR data (ie, droplet counts >10 000 per well) were available for paired CD34-positive and CD34-negative PBMC fractions from 197 (70%) of 284 participants who contributed data to cross-sectional analyses. M tuberculosis complex DNA was detected in PBMCs of 156 of 197 participants with valid dPCR data (79%, 95% CI 74–85). It was more commonly present in CD34-positive than in CD34-negative fractions (154 [73%] of 197 vs 46 [23%] of 197; p<0·0001). Prevalence of dPCR-detected M tuberculosis complex DNA did not differ between QuantiFERON-negative and QuantiFERON-positive participants (77 [78%] of 99 vs 79 [81%] of 98; p=0·73), but it was higher in HIV-infected than in HIV-uninfected participants (67 [89%] of 75 vs 89 [73%] of 122, p=0·0065). By contrast, the proportion of QuantiFERON-positive participants was lower in HIV-infected than in HIV-uninfected participants (25 [33%] of 75 vs 73 [60%] of 122; p<0·0001). Administration of isoniazid preventive therapy reduced the prevalence of dPCR-detected M tuberculosis complex DNA from 41 (95%) of 43 HIV-infected individuals at baseline to 23 (53%) of 43 after treatment (p<0·0001), but it did not affect the prevalence of QuantiFERON positivity (17 [40%] of 43 at baseline vs 13 [30%] of 43 after treatment; p=0·13). Interpretation: We report a novel molecular microbiological biomarker of latent tuberculosis infection with properties that are distinct from those of a commercial interferon-γ release assay. Our findings implicate the bone marrow as a niche for M tuberculosis in latently infected individuals. Detection of M tuberculosis complex DNA in PBMCs has potential applications in the diagnosis of latent tuberculosis infection, in monitoring response to preventive therapy, and as an outcome measure in clinical trials of interventions to prevent or treat latent tuberculosis infection. Funding: UK Medical Research Council.
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| 5. |
- Mulu, Andargachew, et al.
(författare)
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The challenges of COVID-19 testing in Africa : The Ethiopian experience
- 2021
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Ingår i: Pan African Medical Journal. - : Pan African Medical Journal. - 1937-8688. ; 38, s. 1-4
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Tidskriftsartikel (refereegranskat)abstract
- Novel coronavirus disease (COVID-19) is spreading rapidly and creating a huge economic, social and public health challenge worldwide. Although currently an effective vaccine is ready, its distribution is limited, and hence the only currently available lever to reduce transmission is to identify and isolate individuals who are contagious. Thus, testing for SARS CoV-2 has a paramount importance. However, testing in many African countries including Ethiopia has multidimensional growing challenges. Here, we tried to identify, categorize and summarize the challenges of COVID19 testing in Africa from Ethiopian experience.
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| 6. |
- Reepalu, Anton, et al.
(författare)
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Brief Report : Interferon-γ-Inducible Protein 10-A Potential Marker for Targeted Viral Load Monitoring of Antiretroviral Treatment?
- 2020
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - 1525-4135. ; 83:5, s. 475-478
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of surrogate markers for targeting viral load (VL) testing could be an alternative to universal VL testing during antiretroviral treatment (ART) and would allow for more effective resource allocation. We investigated the correlation between levels of HIV RNA and interferon-γ-inducible protein 10 (IP-10) in Ethiopian adults at 12 months after ART initiation. In addition, we specifically investigated differences in IP-10 levels between patients with and without virological suppression.SETTING: Cohort of HIV-positive adults receiving ART at Ethiopian health centers.METHODS: Using a nested case-control design, individuals without virological suppression (HIV RNA ≥ 150 copies/mL) at 12 months after ART initiation were gender-matched with virologically suppressed controls (1:2 ratio). IP-10 levels were correlated with HIV RNA, and the distribution of IP-10 was compared for 3 VL strata: <150 copies/mL (VL < 150), 150-999 copies/mL (VL150-999), and ≥1000 copies/mL (VL ≥ 1000).RESULTS: At 12 months after ART initiation, the following VL distribution was found among 192 individuals (50% women): VL < 150, 122/192 (63.5%); VL150-999, 23/192 (12.0%); and VL ≥ 1000 47/192 (24.5%). IP-10 and HIV RNA levels were positively correlated (r = 0.481; P < 0.0001). Median IP-10 levels for the VL strata were VL < 150: 159 pg/mL [interquartile range (IQR) 121-246], VL150-999: 174 pg/mL (IQR 131-276), and VL ≥ 1000: 343 pg/mL (IQR 190-529), respectively. These differences were statistically significant for VL ≥ 1000 versus VL < 150 (adjusted P < 0.001) and VL150-999 (adjusted P = 0.004), respectively.CONCLUSIONS: IP-10 and HIV RNA levels during ART showed significant correlations, with significantly higher IP-10 concentration in ART recipients with VL ≥ 1000 copies/mL compared to those with suppressed or undetectable VL.
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| 7. |
- Reepalu, Anton, et al.
(författare)
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Drug Resistance in HIV-Positive Adults During the Initial Year of Antiretroviral Treatment at Ethiopian Health Centers
- 2021
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition.METHODS: Participants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis.RESULTS: Among 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis.CONCLUSIONS: Among adults receiving health center-based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.
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| 8. |
- Yang, Xinping, et al.
(författare)
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Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 164:4, s. 805-817
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Tidskriftsartikel (refereegranskat)abstract
- While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms'' are functionally divergent (i.e., "functional alloforms'').
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