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Research Article
Revised

Efficacy of an 8-week course of sofosbuvir and ledipasvir for the treatment of HCV infection in selected HIV-infected patients

[version 2; peer review: 2 approved]
PUBLISHED 21 Sep 2018
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Abstract

Background: With the availability of direct acting antiviral treatment for hepatitis C (HCV), HIV and HCV co-infected patients show comparable treatment responses to HCV-monoinfected patients. An 8-week course of sofosbuvir/ledipasvir (SOF/LDV) is highly effective for the treatment of HCV genotype 1 infection in treatment-naïve mono-infected patients with HCV viral loads <6 million IU/ml. There is limited data on the efficacy of this 8-week HCV treatment regimen in HIV-infected individuals with similar viral loads.
Methods: The study was a retrospective review of HIV-infected adults coinfected with HCV genotype 1 for whom an 8-week course of SOF/LDV was prescribed by providers at two clinics in the Yale-New Haven Health system from November 1, 2014 until April 30, 2016. Treatment efficacy was assessed as the proportion of treatment initiators who achieved a sustained virologic response 12 weeks after completion of therapy (SVR 12).
Results: Nineteen patients met study eligibility criteria and included 14 men (74%); and 12 African-Americans (63%). All patients were on antiretroviral therapy with fully suppressed HIV viral loads and were HCV treatment-naïve. All patients had pre-treatment HCV viral loads <6 million IU/mL. Eighteen patients (95%) completed HCV treatment. Overall, SVR 12 was 95%, with 1 treament failure occurring due to suboptimal adherence.
Conclusion: Among our HIV-infected patient cohort with HCV genotype 1 infection, 95% of those treated with an 8 week course of SOF/LDV achieved SVR 12. This is comparable to the efficacy of the same treatment regimen in patients without HIV infection. This study lends proof of concept to the use of shorter course SOF/LDV treatment for HIV-HCV genotype 1 coinfected patients with viral loads <6 million IU/ml. Larger studies are indicated to validate our findings.

Keywords

Hepatitis C genotype 1, Direct-acting antivirals, HIV, short-course therapy

Revised Amendments from Version 1

This version clarifies the criteria for defining cirrhosis in the two patients included in the study; specifically, these two patients had concordant non-invasive testing scores (APRI and FIB-4) that met cut-offs for cirrhosis; however, both were clinically compensated.  Additionally, comments were updated to highlight that all patients with HIV/HCV should be treated regardless of stage. The database was also revised to clarify inaccuracies.

See the authors' detailed response to the review by David K Wong
See the authors' detailed response to the review by Patrick Ingiliz

Introduction

HIV and hepatitis C virus (HCV) share similar epidemiologic risk factors and routes of transmission, such that among HIV infected individuals, the prevalence of HCV infection is high and estimated at 25% (https://www.cdc.gov/hepatitis/populations/hiv.htm). Among certain risk groups, such as injection drug users with HIV infection, prevalence rates as high as 90% have been reported (https://www.cdc.gov/hepatitis/populations/hiv.htm). HIV infection alters the natural history of HCV disease, such that there are higher and faster rates of progression to liver cirrhosis with its resultant complications; this negative interaction may not be impacted by the receipt of effective antiretroviral therapy (ART)1,2.

Since the sequencing of the HCV genome, there has been an explosion in the number of drugs approved for the treatment of HCV infection. The direct acting antiviral treatment regimens now allow for fully orally administered, well tolerated, and highly effective treatments for HCV infection. However, multiple studies have shown that of the individuals eligible for HCV treatment, few have received treatment3,4. A primary obstacle to the treatment of HCV infection is the exorbitant cost of the treatment regimens5,6. Therefore, cost saving measures including shortened duration of therapy are of interest to patients and their providers7. Emerging data suggests that 8-week rather than 12-week regimens may be effective for HCV treatment among selected patients8,9.

The United States Food and Drug Administration (FDA) approved sofosbuvir/ledipasvir (SOF/LDV) in 2014 for the treatment of chronic HCV genotype 1 infection. The ION-3 study of SOF/LDV that included treatment-naïve non-cirrhotic patients with HCV genotype 1, found that the sustained virologic response 12 weeks after end of therapy (SVR12) was comparable between the 8-week (with and without ribavirin) and 12-week treatment arms in a post hoc analysis for patients who had a pre-treatment HCV viral load (VL) <6 million IU/ml10. Based on this data, the American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines recommend that treatment-naïve, genotype 1 patients without cirrhosis, who are non-black, HIV-negative and with a pre-treatment HCV VL <6 million IU/ml (http://www.hcvguidelines.org/full-report/hcv-testing-and-linkage-care) can be successfully treated with 8 weeks of SOF/LDV. However, the guidelines cite limited data as the reason to not recommend an 8-week SOF/LDV treatment course for HIV-infected patients.

Contemporary HCV treatment trials with directly acting antiviral (DAA) agents have shown that HIV infection status no longer independently impacts treatment outcomes11,12. Therefore, shorter HCV treatment regimens are likely to be as effective in HIV-infected individuals as their non-infected counterparts. Our study describes treatment outcomes of a short (8 week) course of SOF/LDV in HIV/HCV co-infected patients.

Methods

We performed a retrospective review of all HIV and HCV co-infected patients, for whom an 8-week SOF/LDV treatment course was initiated from November 1, 2014 until April 30, 2016. The treatment decision for short course therapy was made by individual clinic providers at two clinics based at Yale Health system in New Haven, CT, USA: Nathan Smith Clinic and the Haelen Center.

Eligibility criteria for the study included all adult (age >18 years) patients with confirmed HIV infection who had HCV genotype 1 infection. Only individuals for whom treatment with an 8-week course of SOF/LDV was intended, were included in the analysis.

Electronic medical records of eligible patients were reviewed. Data collected included demographics, HIV clinical data (CD4 count, HIV VL, antiretroviral treatment (ART)), and laboratory data, including complete blood counts, electrolytes, and liver function tests and biopsy results. Plasma HCV viral loads and genotypes were determined at our lab using COBAS Ampliprep/COBAS Taqman HCV Test, v2.0 (Roche Diagnostics, Indianapolis, IN, USA). Assessment of liver fibrosis stage at time of treatment initiation was determined by one or more of the following: liver biopsy and non-invasive liver fibrosis scores, such as AST to platelet ratio index (APRI)13 and fibrosis-4 (FIB-4) score14. Patient-reported adverse events and reasons for non-completion or discontinuation of treatment were based on documentation in electronic medical records. Data were recorded and analyzed using descriptive statistics in Microsoft Excel, v2013. Overall SVR 12 rate was defined as the proportion of individuals for whom an 8-week treatment course was initiated that had undetectable HCV viral loads 12 weeks after completion of therapy.

Study approval was obtained from the Yale University Human Investigations Committee (number 1506016104).

Results

A total of 19 patients met the study inclusion criteria. Median age was 53 years (IQR 42-73 years); 14 (74%) were males, and 12 (63%) were African-American. The median body mass index was 28.2 kg/m2. The majority (95%) had glomerular filtration rate >60 ml/min. The major risk factor for HIV was injection drug use (53%). Median CD4 T cell count was 678 cells/µL (IQR 458-1004 cells/µL). All patients were on ART, of which non-nucleoside reverse transcriptase inhibitors (43%) followed by integrase strand transfer inhibitor-based regimens (32%) were most common. Thirteen patients (68%) were on tenofovir/emtricitabine (FTC) and 5 (26%) were taking abacavir/lamivudine (3TC). Patients who were on HIV protease inhibitors were receiving tenofovir/FTC. All patients had fully suppressed HIV VLs (Table 1).

Table 1. Baseline demographic and clinical characteristics of 19 HIV and HCV co-infected patients treated with an 8 week course of sofosbuvir and ledipasvir.

CharacteristicValue
Age, median (years; median, IQR)53 (49.5-60.0)
Gender (male; n, %)14 (74)
Race (n, %)
    African-American
    Caucasian

12 (63)
7 (37)
BMI (kg/m2; median, IQR)28.2 (24.5-29.7)
Creatinine clearance (ml/min; n, %)
    <60
    >60

1 (5)
18 (95)
HIV risk factor (n, %)
    IDU
    Heterosexual contact
    MSM
    Blood transfusion

10 (53)
6 (31)
2 (11)
1 (5)
CD4 count (cells/µL; median, IQR)678 (458-1004)
ART regimen (n, %)
    NNRTI
    PI
    INSTI
    Other

8 (42)
4 (21)
6 (32)
1 (5)
ART regimen: NRTI component (n, %)
    Tenofovir/FTC
    Abacavir/3TC

13 (68)
5 (26)
HCV genotype (n, %)
    1a
    1b
    1 unspecified

12 (63)
5 (26)
2 (11)
HCV viral load (IU/ml; median, IQR)869,000 (275,500-1,925,000)
Baseline LFTs (U/L; median, IQR)
    ALT
    AST

45 (30-70)
39 (30.5-62.5)
APRI score (n, %)
    < 0.7
    0.7- < 1.0
    > 1.0

10 (53)
4 (21)
5 (26)
FIB 4-score (n, %)
    <1.45
    1.45- < 3.25
    > 3.25

5 (26)
12 (63)
2 (11)

ALT, alanine transaminase; APRI, AST to platelet ratio index; ART, antiretroviral; AST, aspartate transaminase; BMI, basal metabolic index; FIB-4, fibrosis 4; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IDU, injection drug use; IQR, interquartile range; IU/ml, international units/milliliter; LFT, liver function test; MSM, man who has sex with men; NRTI, nucleoside(tide) reverse transcriptase inhibitor, NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transferase inhibitor; U/L, units/litre; FTC, emtricitabine; 3TC, lamivudine.

Twelve (63%) patients had HCV genotype 1a and 5 (26%) had genotype 1b; in 2 patients, genotype 1 subtype was not done. Median AST and ALT values were 39 (IQR 31-63) units/L and 45 (IQR 32-70) units/L, respectively. All patients had baseline HCV VLs of < 6 million IU/mL and were HCV DAA treatment-naïve. Based on concordant non-invasive scoring (APRI and FIB-4 score), we classified two patients as having cirrhosis, (patients 2 and 3 in database), but both were clinically compensated (Child-Pugh Class A). One patient (patient 15) had discordant APRI (above cut-off) and FIB-4 scores (below cut-off), so was not classified as having cirrhosis.

Eighteen patients (95%) completed 8 weeks of therapy. One patient was non-adherent due to active substance abuse and only completed the first 4 weeks of treatment. Adverse events while on treatment were reported by 6 patients as follows: diarrhea (n=1), abdominal pain (n=1), nausea (n=1), poor appetite (n=1), diffuse joint pains (n=1), and pruritus without rash (n=1). One patient who experienced fatigue due to influenza temporarily discontinued treatment for 7 days, but resumed treatment afterwards. There were no cases of renal insufficiency, including patients who were on HIV protease inhibitors and tenofovir/FTC. Overall, SOF/LDV was well tolerated with no treatment discontinuations due to adverse effects.

All eligible patients had at least one HCV VL assay performed either at week 4 or week 8 of treatment and at 12 weeks following completion of therapy. At week 4 of treatment, 11 of 12 patients for whom there was available data, had undetectable HCV VLs; one patient had viremia that was less than the lower limit of detection of the assay (< 15 IU/ ml). At week 8 of treatment, 11 of 12 patients, who had available HCV VLs, had undetectable HCV VLs. The patient who had detectable HCV VL at week 8 had completed only 4 weeks of therapy and was subsequently non-adherent due to active substance use. In total 18 of the 19 patients achieved SVR 12. Therefore, overall SVR 12 rate was 95% (Table 2). The two patients who had cirrhosis also achieved SVR 12.

Table 2. Treatment outcomes in 19 HIV and HCV co-infected patients treated with sofosbuvir and ledipasvir.

4 week HCV VL
n=121
8 week HCV VL
n=122
SVR 12
n=193
Undetectable
HCV VL (n, %)
11 (92)11 (92)18 (95)

HIV, human immunodeficiency virus; HCV, hepatitis C virus; SVR 12, sustained virologic response 12 weeks after completion of therapy; VL, viral load.

1Data only available for 12 patients; 2Data only available for 12 patients (1 patient only completed 4 weeks of treatment); 3Data obtained from 19 patients 12 weeks after completion of treatment.

TITLE: Baseline demographic and clinical characteristics as well as treatment outcomes of HIV-HCV patients treated with 8-week course of sofosbuvir/ledipasvir
Subject numberAge RangeSexRace/ ethnicityBMIYear of HIV diagnosisHIV risk factoron ART ?CD4 countART base drugClass of ARTNRTI backbone (regimen)Year of HCV diagnosisHCV genotypebaseline (pre-treatment) HCV VLHCV treatment history baseline ALTbaseline ASTCrCl (baseline)cirrhosis present?Decompensated?CHILD PUGH classliver biopsy?liver biopsy (metavir score)fibrospect scoreAPRI scoreFIB 4 scoreweek 4 HCV VLEnd of treatment/week 8 HCV VLHCV VL at week 12 (SVR 12)Discontinued treatment?reason for dc Rx?Adverse event?Type of adverse eventLab abnormality during treatment
160-69MaleBlack221988IVDUYes581DRVPI basedTDF/FTCUnknown1a450000treatment naive2325>60NoNo dataF2-40.4081.88000NoNo
240-49MaleWhite (hispanic)31.61996IVDUYes523EFVNNRTI basedTDF/FTCUnknown1a1670000treatment naive7465>60YesNoAYesF1F0-11.8933.59000NoNo
350-59FemaleBlack25.21985IVDUYes992DRVPI basedTDF/FTC1990s1a4700000treatment naive13522752YesNoAYesF41.6216.77<1500NoYes"dehydrated"
450-59MaleBlack29.11996HSYes714EFVNNRTI basedTDF/FTC20111a532000treatment naive1622>60NoNo0.2511.11000NoYesdiarrhea, abdominal pain
550-59MaleBlack29.41997IVDUYes1121EFVNNRTI basedABC/3TC199712020000treatment naive3039>60NoNo0.6752.47No result in chart 00NoYesacute kidney injury (? Attributable to drug)Cr 1.1->1.3, CrCl still >60 ml/min
640-49Malewhite (non hispanic)26.61995HSYes678OtherOther(other) DTG/DRV/r/TDF20051b869000treatment naive6667>60NoNo1.2092.38No result in chart 106000Not doneYesnon compliant
750-59MaleBlack311991MSMYes891EFVNNRTI basedTDF/FTC19981b3080000treatment naive6560>60NoNo0.8571.910No result in chart 0Yes temporarily but resumed and completed therapy within a weektemporary for 1 week due to fatigueYesfatigue (had the flu)
860-69MaleBlack212013HSYes527RPVNNRTI basedTDF/FTC20131b68800treatment naive3229>60NoNo0.3821.53000NoNonausea, decreased appetite cr up to 1.2 (baselin 1), CrCl still >60ml/min
960-69FemaleBlack291993IVDUYes641DTGINSTIABC/3TC20031a549000treatment naive3637>60NoNo0.5891.830No result in chart 0NoYesitching
1050-59femaleBlack302000IVDUYes288EFVNNRTI basedTDF/FTC20001a1830000treatment naive3636>60NoNo0.9842.85No result in chart 00NoNo
1170-79Malewhite (non hispanic)181997IVDUYes252EFVNNRTI basedTDF/FTC19951a1110000treatment naive4944>60NoNo0.5812.3300NoYesShortness of breath/COPD exacerbation
1240-49Femalewhite (non hispanic)342004IVDUYes1197DTGINSTIABC/3TC20051a956000treatment naive4549>60NoNo0.9681.8No result in chart No result in chart 0NoYesdiffuse joint pains
1350-59maleBlack25.6UnknownIVDUYes357DRVPI basedTDF/FTCUnknown1a789000treatment naive3032>60NoNoF0-10.4031.320No result in chart 0NoNo
1440-49maleBlack36UnknownMSMYes1003ATVPI basedTDF/FTCUnknown1b4500000Null responder4629>60NoYesF20.860.81No result in chart 00NoNo
1550-59MaleWhite (hispanic)23.7UnknownBlood transYes392RALINSTITDF/FTCUnknown1b1750treatment naive280205>60NoNoF0-11.9391.97No result in chart No result in chart 0NoNo
1640-49MaleBlack211990sHSYes1076EFVNNRTI basedABC/3TCUnknown1a94400treatment naive1924>60NoNoF2-40.5272.04000NoNo
1750-59Malewhite (non hispanic)28.91990sIVDUYes1004EVGNNRTI basedTDF/FTCUnknown1a101000treatment naive9359>60NoNoF1F0-10.6571.32000NoNo
1850-59Femalewhite (non hispanic)261996HSYes1023EVGINSTITDF/FTCUnknown141500treatment naive2334>60NoNo0.3291.17000NoNo
1960-69MaleBlack28.22002HSYes367DTGINSTIABC/3TC20021a2520000treatment naive14791>60NoNo1.42.640NoNo
Dataset 1.Spreadsheet data showing baseline demographic and clinical characteristics, as well as treatment outcomes, of HIV-HCV patients treated with 8-week course of sofosbuvir/ledipasvir.

Discussion

HIV and HCV infections are often referred to as syndemics as they share similar routes of transmission and impact populations that have similar demographic and socio-economic profiles15. The presence of HIV infection confers a risk for accelerated progression of liver disease, even when HIV is virally suppressed16. For these reasons, it is important to ensure treatment of HCV for all HIV-infected persons, regardless of disease stage. Multiple studies have shown that HIV co-infection is no longer a significant predictor of poor HCV treatment outcomes, such that cure rates among individuals infected with HIV are similar to those who are uninfected11,17.

There is interest in shorter HCV treatment durations for a number of reasons: the prohibitive cost of newer DAAs18, and issues of adherence and potential development of resistance or toxicity. Kowdley et al. showed in a post hoc analysis that an 8-week treatment regimen of SOF/LDV resulted in a high SVR 12 rate among non-cirrhotic HCV infected individuals with genotype 1 infection that was non-inferior to an 8-week regimen with ribavirin or a 12-week regimen without ribavirin10. Lower relapse rates were observed among patients receiving 8 weeks of SOF/LDV who had baseline HCV RNA levels <6 million IU/ml (2%; 2 of 123). However, this study did not include HIV-infected individuals.

In a subsequent real-world multi-national retrospective study of 634 patients, an 8-week course of SOF/LDV resulted in an overall SVR 12 of 98.1% in non-cirrhotic treatment-naïve individuals regardless of HCV VLs. This study included 16 HIV-infected individuals, and for those with VL >6 million IU/ml, 100% achieved SVR 129. Unlike the previous study, this study found that pre-treatment HCV VL >6 million IU/ml in a subset of patients with HIV infection did not affect treatment outcomes, including relapse rates.

Our study, showing an SVR 12 of 95%, is similar to the rates observed in a German cohort of 28 HIV-HCV co-infected patients, who showed a 96% response rate to 8 week therapy using SOF/LDV (GECCO-01 study)8. All patients in the trial were on antiretroviral therapy with a median CD4 count of 604 cells/mm3. However, the cohort consisted of predominantly Caucasian and male patients (89%). Our patient demographic was different with more women (26% versus 11%), and comprised a majority of African-American patients (63%).

It is important to highlight that not all DAA-based 8 week treatment courses for HIV-infected patients have yielded satisfactory results. The phase 3 ALLY-2 study, explored 8-week and 12-week SOF/daclatasvir treatment courses in HIV-infected individuals with HCV genotypes 1-419. For treatment-naïve patients with HCV genotype 1, SVR 12 was 96% in the 12-week arm and 76% in the 8-week arm. However, it was observed that patients with HCV VL <2 million IU/ml performed better than those with viral loads >2 million IU/ml (SVR 12 of 100% versus 62%) supporting excellent efficacy with lower viral loads19.

Our 95% SVR 12 rate in individuals placed on short course treatment may be attributable to certain factors: excellent adherence (supported by well controlled HIV infection) and selection of individuals with low HCV viral loads, factors that are associated with higher likelihood of cure17,20. It is remarkable that 26% of subjects were women and almost two-thirds were African-American; two groups that are often under-represented in HCV treatment studies, and this thereby increases the generalizability of the study results. The two individuals with cirrhosis also achieved excellent treatment results. In spite of the small number of patients in our study, the concordance of our findings with the European cohort in the GECCO-01 trial, as well as the multi-center study reported by Kowdley et al, lends support to its validity.

A limitation of our study is that it was retrospective, therefore data captured was dependent on the quality of documentation by patient providers. Our patient demographic may not be representative of patients in settings different from ours. There may be a treatment selection bias, whereby patients who were more likely to adhere to therapy and had characteristics favorable to achieving an optimal response were initiated on therapy by their clinic providers. Due to the low number of patients with cirrhosis in our cohort, it is not advisable to extend the conclusions to this subgroup.

In summary, our study provides support for the use of an 8-week course of SOF/LDV as an effective treatment option for HIV and genotype 1 HCV co-infected individuals with HCV viral loads <6 million IU/ml.

Data availability

Dataset 1: Spreadsheet data showing baseline demographic and clinical characteristics, as well as treatment outcomes, of HIV-HCV patients treated with 8-week course of sofosbuvir/ledipasvir. doi, 10.5256/f1000research.11397.d21852221

Ethical statement

This medical review was approved by Yale University Human Investigations Committee (number 1506016104); individual patient consent was not required in this retrospective chart review.

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Ogbuagu O, Hao R, Virata M et al. Efficacy of an 8-week course of sofosbuvir and ledipasvir for the treatment of HCV infection in selected HIV-infected patients [version 2; peer review: 2 approved]. F1000Research 2018, 6:620 (https://doi.org/10.12688/f1000research.11397.2)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 2
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PUBLISHED 21 Sep 2018
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Reviewer Report 24 Sep 2018
David K Wong, Immunodeficiency Clinic, University Health Network, Toronto, ON, Canada;  University of Toronto, Toronto, Canada 
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Wong DK. Reviewer Report For: Efficacy of an 8-week course of sofosbuvir and ledipasvir for the treatment of HCV infection in selected HIV-infected patients [version 2; peer review: 2 approved]. F1000Research 2018, 6:620 (https://doi.org/10.5256/f1000research.17847.r38623)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Reviewer Report 30 Aug 2018
David K Wong, Immunodeficiency Clinic, University Health Network, Toronto, ON, Canada;  University of Toronto, Toronto, Canada 
Approved with Reservations
VIEWS 19
General:
This is a small retrospective study that adds to the evidence that those with HCV (genotype 1)-HIV co-infection and low viral load can be treated successfully with 8 weeks of Sofosbuvir/Ledipasvir. Adherence matters as the one treatment failure ... Continue reading
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CITE
HOW TO CITE THIS REPORT
Wong DK. Reviewer Report For: Efficacy of an 8-week course of sofosbuvir and ledipasvir for the treatment of HCV infection in selected HIV-infected patients [version 2; peer review: 2 approved]. F1000Research 2018, 6:620 (https://doi.org/10.5256/f1000research.12302.r24844)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 21 Sep 2018
    Merceditas Villanueva, Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, 06510, USA
    21 Sep 2018
    Author Response
    General:
    This is a small retrospective study that adds to the evidence that those with HCV (genotype 1)-HIV co-infection and low viral load can be treated successfully with 8 weeks of ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 21 Sep 2018
    Merceditas Villanueva, Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, 06510, USA
    21 Sep 2018
    Author Response
    General:
    This is a small retrospective study that adds to the evidence that those with HCV (genotype 1)-HIV co-infection and low viral load can be treated successfully with 8 weeks of ... Continue reading
Views
18
Cite
Reviewer Report 05 Jun 2017
Patrick Ingiliz, Center for Infectiology, Berlin, Germany 
Approved
VIEWS 18
Ogbuago and coworkers provide a small study on 19 HIV-HCV coinfected individuals that were treated with an 8-weeks course of sofosbuvir and ledipasvir. Overall, the SVR rate is 95% with only one individual not responding who was in-adherent. The study, ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Ingiliz P. Reviewer Report For: Efficacy of an 8-week course of sofosbuvir and ledipasvir for the treatment of HCV infection in selected HIV-infected patients [version 2; peer review: 2 approved]. F1000Research 2018, 6:620 (https://doi.org/10.5256/f1000research.12302.r22470)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 21 Sep 2018
    Merceditas Villanueva, Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, 06510, USA
    21 Sep 2018
    Author Response
    In response to Dr Ingiliz's comments:
    1. It is correct that our cohort consisting of predominantly AAs, current or ex-IDUs, with high median BMI, and who are HIV co-infected
    ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 21 Sep 2018
    Merceditas Villanueva, Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, 06510, USA
    21 Sep 2018
    Author Response
    In response to Dr Ingiliz's comments:
    1. It is correct that our cohort consisting of predominantly AAs, current or ex-IDUs, with high median BMI, and who are HIV co-infected
    ... Continue reading

Comments on this article Comments (0)

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Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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