CROI 2019: Highlights of Viral Hepatitis - IAS-USA
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CROI 2019: Viral Hepatitis Volume 27 Issue 1 April 2019
Invited Review
CROI 2019: Highlights of Viral Hepatitis
Anne F. Luetkemeyer, MD; David L. Wyles, MD
At the 2019 Conference on Retroviruses and Opportunistic Infections (CROI), Several studies evaluated interven-
there was a major focus on hepatitis C virus (HCV) elimination and improv- tion packages to improve engagement
ing each component of the hepatitis C care cascade. Many interventions along the care cascade. The strategy
showed promising improvements in diagnosis and linkage to care. Settings of care facilitation, which included mo-
with robust access to direct-acting antivirals (DAAs) continue to demonstrate tivational interviewing and patient-spe-
the role of HCV treatment as prevention. However, substantial barriers to cific needs assessment, had a mod-
accessing curative therapy remain. Reinfection after treatment presents an est impact in improving engagement
important barrier to elimination, particularly in some populations of men in the steps of the HCV care cascade,
who have sex with men (MSM). MSM without HIV infection are at an elevated with more impact seen in men receiv-
risk for sexual acquisition of HCV, and several studies reported HCV rates that ing active facilitation than in controls
were as high as those seen in MSM living with HIV. There was also a focus on (Abstract 578). Random assignment to
HCV and HBV in pregnant women. Rates of HCV infection in women of child- nurse case management improved link-
bearing potential have increased, making prenatal diagnosis a priority. In the age to care for HIV/HCV coinfected pa-
first study of HCV treatment during pregnancy, sofosbuvir/ledipasvir started tients (47% vs 25% without case man-
at 28 weeks of gestation led to cure in 8 pregnant women. Hepatitis B virus agement), but was not sufficient to im-
(HBV)-active antiretrovirals are generally effective in suppressing HBV but have pact time to treatment initiation. Over-
low rates of surface antigen loss despite long term treatment. Initial results all cure rates remained low (≤5%) (Ab-
from novel laboratory assessments of intrahepatic HBV viral infection events stract 580). Leveraging non-specialists
were presented, hopefully paving the way for more effective HBV treatment remains an important means to im-
strategies to control and potentially cure HBV. prove HCV uptake. In King County, Wash-
ington, a community-based approach
Keywords: CROI, 2019, hepatitis, pregnancy, HBV, HCV, acute, reinfection using a combination of emergency med-
ical responder interventions, active link-
Hepatitis C Virus Care Cascade Columbia Hepatitis Testers Cohort (Ab age to care, and practitioner education
stract 582). Importantly, rates of sus- tripled the number of individuals tested
With the increasing availability of direct- tained viral response at 12 weeks (SVR for HCV and increased HCV treatment
acting antivirals (DAAs) and focus on 12) were similarly high in recent PWID tenfold over 4 years (Abstract 583). Train-
HCV elimination, there is continuing at- (91%) and never PWID (92%), renforcing ing 49 primary care practitioners in HCV
tention to improving engagement along that PWID can be successfully treated care led to treatment initiation in more
the hepatitis C virus (HCV) care cas- when able to access therapy. One effec- than 700 individuals with HCV infec-
cade, particularly for the most vulner- tive strategy to improve diagnosis and tion, demonstrating the important role
able and difficult to access individuals engagement of PWID involved incentiv- non-specialists can play in improving
living with HCV infection. Jail remains izing PWID with HCV infection to recruit HCV treatment access (Abstract 587). A
an important venue for HCV infection other PWID for HCV testing and link- meta-analysis demonstrated that task
diagnosis with 16% of inmates at the age to care. A third of PWID were able shifting to non-specialist achieved simi-
Dallas County jail identified as HCV anti- to recruit at least 1 colleague, and this larly high cure rates of 92% compared
body positive on opt-out testing, 75% of proved to be a highly impacted group, with specialty care, in PWID and in the
whom were HCV viremic. Despite high 87% of whom were HCV antibody posi- general population. HCV testing and
rates (85%) of uptake of HCV education tive (Abstract 575). Unfortunately, there treatment in non-referral settings (de-
during incarceration, linkage to HCV was substantial drop off in those linked centralization) led to higher uptake of
treatment after discharge was very low to HCV care and ultimately being cured. HCV testing (88% vs 47%, respectively),
(IAS–USA Topics in Antiviral Medicine
remain for patients to access HCV treat- particularly when shorter incubation Acute HCV and Epidemiology in
ment. An HIV/HCV coinfection cohort times were used,1 but data on perfor- High-Risk Populations
at an Atlanta public health hospital mance in HIV-infected populations are
found 53% of HIV/HCV coinfected indi- limited.2 The European PROBE-C (Natural His-
viduals had not been treated for HCV; A simple laboratory-based assay to tory and Treatment of Acute Hepatitis C
the main barriers identified were alco- infer recent HCV infection would be a Virus I (HCV) in HIV-positive Indivi-
hol and substance use (60% of those welcome addition to HCV epidemio- duals) cohort again demonstrated low
not treated) and poor HIV control (Ab- logic studies. Avidity assays take ad- spontaneous clearance rates (12%) in
stract 573). Similarly, poor HIV control vantage of the fact that antibodies pro- acute HCV infection in PLWH (Abstract
and well as Medicare (vs Medicaid) duced early in the course of chronic 576). Evaluation for spontaneous clear-
were associated with lack of HCV treat- ance was limited by treatment initiation
ment in a Johns Hopkins HIV/HCV co- A 2-log10 decline in HCV during the first year after acute HCV di-
hort (Abstract 574). agnosis, which occurred at a median of
RNA at 4 weeks after 14 weeks in those taking interferon alfa
Impact of Opioid Use on HCV acute HCV diagnosis was (n=277) and a median of 44 week in
those taking DAAs (n=47). Notably, a
and Fibrosis associated with sponta- 2-log10 decline in HCV RNA at 4 weeks
In vitro, fentanyl was associated with neous clearance (P ≤.001) after acute HCV diagnosis was signifi-
increased HIV and HCV viral replication, and identified 96% of cantly associated with spontaneous
which provides yet another potential clearance (P≤.001) and identified 96%
route by which the opioid epidemic im- those who cleared the of those who cleared the virus without
pacts PLWH or individuals with HCV virus without treatment. treatment. This provides useful guid-
infection, or both (Abstract 618). A Mi- ance for practitioners whose patients
ami cohort found an association of ad- This provides useful who do not want to wait up to 12 to
vanced fibrosis (Fibrosis-4 score [FIB-4] guidance for patients 16 weeks to monitor for spontaneous
>1.45) with fentanyl use (odds ratio clearance (per current American Asso-
[OR], 1.67; P=.0035) and HIV infection
who do not want to wait ciation for the Study of Liver Diseases/
(OR, 2.25; P=.0025); however, it was not up to 12 to 16 weeks to Infectious Diseases Society of America
clear if these analyses accounted for con- [AASLD/IDSA] guidance),3 during which
monitor for spontaneous
comitant viral hepatitis (Abstract 617). time they may infect others or become
clearance lost to follow-up.
HCV Diagnostics
The epidemiology of incident HCV
infections, such as HIV or HCV, tend infection in HIV-negative men who have
HCV core antigen testing is generally a to bind less tightly to antigens than sex with men (MSM) is not well-char-
faster and less expensive alternative to antibodies that appear later. Charac- acterized. An analysis from England ex-
HCV RNA testing to confirm HCV infec- teristics of a modified HCV antibody amined incident HCV infection in MSM
tion and identify acute HCV infection. enzyme-linked immunosorbent assay by HIV status (Abstract 598). Among 40
When used by a London sexual health (ELISA) (Genedia 3.0 HCV ELISA) were recent HCV infections in MSM identified
clinic, core antigen testing identified evaluated in samples from 875 sero- from 5 clinical sites, 16 (40%) of infec-
95% of acute HCV infections. Of the positive individuals, including 116 with tions were in HIV-uninfected MSM. This
4 missed, 3 had alanine aminotrans- a well-defined seroconversion, being group was younger (34 years vs 44 years
ferase (ALT) levels above 300 IU/L and followed up in prospective cohort stud- old for HIV infected), frequently on pre-
1 had an ALT level 33 IU/L, leading to ies of PWID (Abstract 601). Using an exposure prophylaxis (81%), and tended
HCV RNA testing. Notably, using HCV avidity index (optical density ratio of dis- to have higher risk sexual behaviors (eg,
antibody and ALT elevation alone would sociated well/standard assay well) of more partners, group sex, and fisting).
have missed 47% (37/82) of the acute less than 40% identified samples from In contrast to HIV sexual transmission,
HCV diagnoses (Abstract 586). Of note, participants with a mean duration of there was little awareness of the poten-
HCV core antigen testing in not ap- infection of 113 days (range, 84-146 tial for HCV sexual transmission. Injec-
proved for use in the United States. days) with a low false recent rate (FRR) tion drug use was identified as a risk
The Ora-Quick rapid HCV antibody test of 0.4% (long-term infections classified factor in 1 of 3 of both HIV-infected
yielded a markedly low sensitivity of as recent). Although the modified assay and HIV-uninfected groups. Phyloge-
6% in HIV/HCV coinfected individuals performed equally well for genotype 1 netic analysis based on whole genome
compared with 100% in those with- and 3 infections, HIV infection, par- sequencing identified extensive mixing
out HIV; specificity was 100% in all ticularly in individuals with CD4+ cell within clusters of sequences from HIV-
groups (Abstract 584). Other groups counts below 200/µL, was associated infected and HIV-uninfected MSM.
have reported lower sensitivity of the with a significant increase in the FRR at A Thai study suggested a dramatic
Ora-Quick rapid HCV antibody test, a 40% avidity index. increase in HCV incidence among HIV
42CROI 2019: Viral Hepatitis Volume 27 Issue 1 April 2019
infected MSM after 2014 (0.37/100 per- casts at http://www.croiwebcasts.org/? groups included a higher prevalence of
son-years pre-2014 vs 2.21/100 person- link=nav&linkc=home. genotype 1a (37% vs 15%, respectively)
years in 2014-2018) and was strongly and 4 (43% vs 10%, respectively) infec-
associated with new syphilis infections tion in coinfected participants; the pre-
HCV Treatment and Treatment as
(Abstract 599). An analysis from the valence of high HCV RNA and cirrho-
Prevention
HPTN (HIV Prevention Trials Network) sis were similar between the groups.
078 study identified a high prevalence Two abstracts focused on performance HIV was well controlled with 95% sup-
HCV seropositivity regardless of HIV sta- of elbasvir/grazoprevir (EBR/GZR) in pressed on antiretroviral therapy (ART)
tus in MSM (20% HIV infected, 16% HIV diverse population outside of clinical and a median CD4+ cell count of 685/
uninfected) from Boston, Baltimore, Bir- trials. In a report looking at combined uL. In unadjusted analyses, SVR12 was
mingham, and Atlanta (Abstract 596). lower in the coinfected group (90% vs
The HCV prevalence in HIV-uninfected These cohort data 94%, respectively; P=.035). The differ
MSM is substantially higher than prior support prior results ence persisted in a modified intention-
estimates and may stem from the re- to-treat analysis excluding those lost
cruitment approach in HPTN 078, which demonstrating similar to follow-up (94% vs 97%, respectively;
used respondent-driven sampling to tar- DAA treatment response P=.029). Although HIV infection was as-
get HIV-infected MSM without viral sup- sociated with non-SVR in a univariate
pression (possibly also engaging high- rates outside clinical analysis; after accounting for HCV gen-
risk HIV-uninfected MSM). trials and in key popula- otype and cirrhosis status in a multi
Using a phylodynamic approach based variate analysis the impact of HIV co-
on epidemiologic data and 213 non-
tions such as people who infection was lost (OR, 1.04, 0.54-2.02).
structural protein 5B gene sequences inject drugs and people These cohort data support prior results
from PWID detected during chronic living with HIV demonstrating similar DAA treatment
infection (classical group) and from response rates outside clinical trials
MSM with or without HIV infection de- outcomes from the HEPAVIR-DAA (HIV/ and in key populations such PWID and
tected during acute infection (new HCV) and GEHEP (Group for the Study PLWH.
group), disease transmission character- of Viral Hepatitis-MONO cohorts, re- Treatment as prevention of trans-
istics were estimated (basic reproduc- sponses to 12 to 16 weeks (with or with mission is well established for HIV, and
tion ratio [Ro] and period of infectivity) out ribavirin) of EBR/GZR were ana- recent data from Dutch and Swiss HIV
(Abstract 594). According to the model, lyzed for 266 persons with SVR12 da- cohorts indicate this to also be an ef-
transmission occurs more frequently ta available (Abstract 561). Notable as- fective approach to decreasing HCV
from MSM with a Ro of 2.35 (compared pects of the cohort included a high pre- transmission in high-risk populations
with 1.8 for PWID) although the period valence of PWID (53%) and HIV coin such as HIV-infected MSM.5,6 An analy-
of infectivity is longer in the classical fection (27%). Consistent with regis- sis presented by Garvey and colleagues
scenario (18 vs 3 months in the new trational studies, a high SVR12 of 96% from 3 large HIV clinics in London lends
group). The origin of the MSM epidemic was seen and only 2.3% experienced further support to the notion that ag-
was estimated to be in 2001. virologic failure. Similar SVR12 data gressive HCV treatment can reduce in-
A large phylogenetic analysis of HCV- were seen in PWID (94%; P=.43). As cident HCV infections (Abstract 85). The
infected PWID (n=486) from 4 cities in has been described, numerically lower study period was from June 2013 to July
India demonstrated extensive cluster- SVR12 was seen in genotype 1a (92%), 2018 with data collection at 6 month
ing, with 52% of samples belonging to although there were relatively few cases intervals focusing on new HCV infec-
a cluster and large cluster sizes (mean (n=64) and resistance-associated sub- tions; a uniform testing approach was
7.4; 6 clusters had >10 samples) (Ab- stitution (RAS) testing was not uniormly not used at across the sites. Incident
stract 593). Seven of 19 clusters (ge- performed. If available, RAS testing is HCV infections were split into first-time
netic distanceIAS–USA Topics in Antiviral Medicine
(excluding reinfections; 1.5/100 per- those from within clusters was 2018 (ra- Obstetrics and Gynecology and US Pre-
son-years—0.3/100 person-years) was tio, 1.35). Although this may be largely ventive Services Task Force have not yet
seen from the second half of 2015 due to the aggressive treatment of HCV adopted this recommendation.
(peak) to the first half of 2018 (last time in MSM with HIV infection in Amster- Chaillon and colleagues demon-
period). However, 2 disturbing trends dam (eliminating the pool for internal strated that universal screening of preg-
were noted: 1) the proportion with re- transmissions) it raises concerns for ex- nant women in the United States is cost-
infection had been increasing in recent ogenous HCV reintroduction. effective, including at the US national
years (43%-47% in last 2 6-month time- prevalence of 0.7%, and is even more
periods) and 2) the overall incidence did HCV Reinfection cost effective in parts of the United
not decline in the last 3 time periods States where HCV prevalence in preg-
studied (0.5-0.6/100 person-years) sug- The likelihood of HCV reinfection fol- nancy is as high as 8% (incremental
gesting perhaps an underlying high-risk lowing either spontaneous clearance cost-effectiveness ratio [ICER] of $5,288
population without adequate treatment or after SVR12 varies based on the risk at an F2 treatment threshold). Univer-
penetration. As has been seen in other factors for initial infection. Among the sal screening of pregnant women is
cohorts, an increase in other sexually major risk groups for HCV infection, anticipated to detect HCV in 33,000 US
transmitted infections was seen over PWID have traditionally been viewed women (Abstract 589). In a retrospec-
time period, suggesting decreased risk as a population at high risk for reinfec- tive evaluation of more than 10,000 preg
behaviors were unlikely to have contrib- tion. However, several European cohorts nant women from a large mid-Atlantic
uted to the fall in new HCV infections. have found high HCV reinfection rates healthcare system, overall HCV screen-
Decreases in time to starting treatment in MSM with HIV infection.7 Few data ing rate was 30%, and 20% of the women
were seen over the study period, from a are available from contemporaneous with HCV antibody positive test results
mean of 41 months in 2013 to 3 months cohorts in the United States. Fierer and had no reported HCV risk factor. Notably,
in 2018, but relied heavily on clinical tria- colleagues presented data from the
laccess. Reliance on treatment through New York Acute Hepatitis C Surveil- 8 of 8 pregnant women
clinical trials to provide key public health lance Network, spanning 2000 to 2018
interventions is not sustainable and that suggested similarly elevated rates
treated with ledipasvir/
calls for a change in NHSE policies that of HCV reinfection in MSM with HIV sofosbuvir achieved
restrict treatment for both acute and re- infection (Abstract 86). The cohort con- sustained viral response
current HCV infections. sisted of 304 MSM with HIV infection
A number of country-wide efforts who were predominantly white (82%) at 12 weeks. Given the
targeting enhanced diagnosis and im- with a median age of 45 years. There hepatitis B and HIV
mediate, universal treatment of HCV in were 845 person-years of follow-up analogies, there is little
MSM with HIV infection have demon- with a median follow-up duration of 2.2
strated dramatic short-term decreases years. Thirty-eight reinfections were doubt DAA treatment
in HCV incidence and prevalence. Al- captured at median of 1.9 years post will be effective in
though encouraging, HCV transmissions clearance for an incidence of 4.4 per
from outside the cohort could hamper 100 person-years, which is in the range
prevention of mother-
elimination efforts. A phylogenetic an- seen in European cohorts and generally to-child transmission
alysis of 174 genotype 1a E1-E2 HCV higher than seem in PWID. There was of HCV
sequences from HIV-infected MSM in no difference in reinfection rate based
Amsterdam attempted to determine on mode of prior clearance, whether there were racial disparities in screen-
the date of sequence introduction and spontaneous or treatment induced, al- ing; women undergoing testing were
further whether the introduction oc- though numbers are small and con- more likely to be African-American than
curred from within the cohort or ex- fidence intervals wide. In contrast, white (47% vs 33%, respectively) de-
ternally (Abstract 597). Ten transmis an Australian HIV/HCV observational spite a higher percentage of white
sion clusters with more than 5 se- coinfection cohort reported lower rein- women testing HCV antibody positive
quence members were identified. The fection rates after cure at 0.81 per 100 (71% vs 21%, respectively) (Abstract 586).
estimated dates of introduction ranged person-years; of note, all 5 reinfections These data highlight the need for more
from 1993 to 2005, placing them in a occurred in MSM (Abstract 577). uniform guidance and uptake in HCV
similar timeframe to the French phylo screening of pregnant women.
dynamic data. The authors then ana- HCV in Pregnancy Perinatal transmission of HCV occurs
lyzed incident infections by year and in approximately 5% to 6% of births of
determined the ratio of new infection HCV infection in pregnant women has mothers with HCV viremia, with HIV
originating from a within transmission doubled from 2009 to 2014,8 leading to coinfection increasing this transmission
cluster (internal) versus outside (exter- AASLD/IDSA to recommend universal rate. In one of the most anticipated hep-
nal). Notably the only year for which HCV screening in pregnancy as of Sep- atitis presentations at CROI, Chappell
external transmissions outnumbered tember, 2018. The American College of and colleagues presented the first data
44CROI 2019: Viral Hepatitis Volume 27 Issue 1 April 2019 of DAA-based treatment of HCV during established epidemiologic link between events (assessed by ICD-9/10 codes) in pregnancy (Abstract 87). Extrapolating HCV infection and the development of HCV treated (n=32,575) vs a propen- from HIV and hepatitis B virus (HBV) diabetes mellitus. Although few data sity-matched HCV untreated group of infection experience, it is expected that are available on the possible beneficial veterans without HIV (Abstract 570). By therapy that reduces the maternal viral effects of HCV cure on diabetes preven- design the groups were well matched load to zero would dramatically reduce tion and improved insulin sensitivity, for diabetes, hypertension, and smok- HCV perinatal transmission. several case reports have suggested a ing status; statin use was higher in the A phase I study evaluated 12 weeks of positive effect. untreated group, although the absolute ledipasvir/sofosbuvir for genotypes 1, 4, Using the ERCHIVES (Electronically difference was less than 1%. FIB-4 score 5, and 6 infection in pregnant women. Retrieved Cohort of HCV Infected Vet- was higher in the treated group at base- Key exclusions included HIV coinfection erans), Butt and colleagues assessed in- line, although the absolute difference and cirrhosis. Treatment was initiated at cident diabetes mellitus (DM) at more was modest (1.95 and 1.70, respectively; 23 to 24 weeks of gestation with follow- than 12 weeks after completion of HCV P
IAS–USA Topics in Antiviral Medicine
in HIV/HCV-coinfected persons (n=35) later after DAA treatment (Abstract both groups (FIB-4 ≤3.25 or >3.25),
and compared levels over time with a 566). Following treatment dramatic and HBV infection was associated with
well-controlled HIV-monoinfected group improvements in eGFR were seen in a relatively elevated risk in those with a
(n=37) (Abstract 567). At baseline LDL groups with stage 3 (49.8 to 79.7; P< FIB-4 score of 3.25 or lower (HR, 4.93
levels were significantly lower in those .001) and stage 4 or 5 (23.9 to 73.9; vs 2.12). In terms of HIV control, there
with HCV coinfection, though there was PCROI 2019: Viral Hepatitis Volume 27 Issue 1 April 2019
for Disease Control and Prevention infected persons on ART with preserved vaccination alone, due to the unexpect-
(CDC)-C diagnosis (P200/µL) in Taiwan edly low rate of MTCT in the vaccination/
HBV viremia despite HIV suppression (Abstract 622). No difference was seen immunoglobulin-only arm.12 However,
on tenofovir-based ART has been de- in the primary endpoints of anti-HBs these data are reminder that MTCT of
scribed, but the etiology is not well un- HBV can essentially be eliminated with
derstood. An analysis of tenofovir con Mother-to-child prompt infant immunoglobulin and vac-
centrations in dried blood spots demon- cination combined with maternal TDF.
strated lower tenofovir concentrations transmission of HBV can The impact of maternal TDF on MTCT
in patients with HBV viremia and HIV essentially be eliminated may vary depending on the specific
suppression. This suggests that lower population risk for transmission.
ART adherence may be responsible for with prompt infant Another study examined the im-
HBV viremia and that there is a dif- immunoglobulin and pact of maternal HBV infection on birth
ferential ART adherence threshold for outcomes in an older study (HPTN 046)
suppression of HBV and HIV. No HBV
vaccination combined evaluating nevirapine to prevent MTCT
drug resistance mutations were re- with maternal TDF of HIV in sub-Saharan Africa. A total of
ported (Abstract 626). 88 (4.3%) of mothers with HIV infection
response 10 mIU/mL or more 4 weeks were HBsAg positive, 10 of whom had
after the last dose (88.2% vs 96.9% for high HBV DNA (>106 IU/mL). More than
HBV Reactivation and Revaccination
standard and high dose, respectively; 80% of mothers were on HIV medica-
The US Food and Drug Administration P=.36). However, geometric mean titers tions; however, 48% were on ART that
(FDA) raised concerns about risk of of anti-HBs were significantly higher did not contain lamivudine, and none
HBV reactivation in those with resolved at all time points in the double-dose were on TDF-based ART. Infants born
or current HBV infection during HCV group. Conclusions from these results to mothers with HIV infection who had
treatment with DAAs with a black box are limited by the small study size. high HBV DNA levels were more likely
warning issued in 2017.10 A London HBV vaccine using a novel TLR9 adju- to have low birth weight (30%) than
cohort examined the risk for HBV reac- vant (HEPLISLAV-B) has demonstrated those without HBV (10%) or with low
tivation during HCV treatment in 271 improved antibody responses and are HBV DNA (6%) (P=.04), and HBV vire-
HIV/HCV-coinfected individuals taking starting to be evaluated in HIV-infected mia appeared to have a dose-respon-
DAAs. In 35% (96/271) HBV core an- populations. sive relationship to low birth weight.
tibody (HBcAb) was positive; of these High HBV DNA level was also associ-
6 were HBsAg-positive, 56 had HBsAb ated with MTCT of HIV in 2 of 10 in-
HBV in Pregnancy
above 10 IU/mL, and 26 had only iso- fants. These data suggest that reduc-
lated HBcAb-positive; 98% were taking The iTAP (Maternal Antiviral Prophy- tion of maternal HBV DNA level may
at least 1 HBV-active ART medication. laxis to Prevent Perinatal Transmission have benefits beyond maternal health
Of the 14 taking lamivudine as the of Hepatitis B Virus in Thailand) study and reduction of infant infection, but
only HBV-active ART, 2 added teno- randomly assigned HBV envelope anti- this has to be tempered by a small num-
fovir and 6 started entecavir. No HBV gen positive pregnant Thai women to ber of mother-infant pairs, particularly
reactivation occurred in any of the receive tenofovir disoproxil fumarate in the group with high HBV DNA levels.
participants, including the 6 with a (TDF) or placebo starting at 28 weeks of (Abstract 41LB)
positive HBsAg (Abstract 628). Given gestation to evaluate the impact of TDF
the small sample size, it is not clear if on MTCT, with added HBV immuno-
Intrahepatic Evaluation of HCV
the addition of tenofovir or entecavir is globulin and HBV vaccination provided
and HBV
warranted, particularly in those with- to all infants. In an analysis of maternal
out surface antigen. Overall, the lack of HBV DNA presented at this year’s CROI, Two studies used the novel technique
reactivation during HCV DAA therapy is 88% of women randomized to TDF had of single cell laser capture microdis-
consistent with results of a meta-anal- HBV DNA less than 200,000 IU/mL at section (scLCD) to examine viral- and
ysis of HCV monoinfected individuals delivery, a threshold that has been as- immune-based phenomena at the he-
demonstrating no clinically significant sociated with lower risk of maternal to patocyte level in 1) chronic HCV in-
HBV reactivation in the absence of child HBV transmission (Abstract 629). fection early during DAA treatment
HBsAg positivity.11 Although 12% of women had HBV DNA (Abstract 89) and 2) chronic HBV in-
Optimal approaches to revaccination levels above 200,000 IU/mL at delivery, fection (Abstract 91). In a sub-study of
for HBV infection after non-response no HBV transmission occurred from A5329 that evaluated paritaprevir/rito-
to a first series in HIV-infected persons any TDF-treated mother to their infant, navir/ombitasvir plus dasabuvir (PrOD)
remain unclear. A randomized trial of whereas 3 infections occurred in the therapy for genotype 1 HCV infection,
standard dose (20 µg) versus double placebo arm. The previously published paired liver biopsy specimens (imme-
dose (40 µg) Engerix-B given at 0, 1, trial was not able to demonstrate a diately before and after 1 week of ther-
and 6 months was carried out in HIV- significant benefit of TDF over infant apy) from 5 HIV-coinfected participants
47IAS–USA Topics in Antiviral Medicine
were evaluated by scLCD for intracel- DNA) in infected cells that, even under and was examined in a HIV clinic co-
lular HCV RNA, interferon-stimulated suppressive nucleoside-based therapy, hort (Abstract 621). Twenty patients
gene (ISG) expression, and drug lev- serves as a latent reservoir of infec- had clear evidence of loss of HAV im-
els. Detailed plasma viral kinetics and tion. As novel treatment approaches munity; 15 with documented vaccina-
drug levels were collected concom- aimed at HBV cure are advanced, a tion and 5 with prior positive antibody
itantly. All participants had similar HCV better characterization of intrahepatic titers. Although CD4+ cell count was
(treatment-naive, genotype 1a HCV in- HBV expression is needed. In particu- relatively preserved (mean, 376 ±85/
fection, and without cirrhosis) and HIV lar, immune-based therapies aimed µL) only 50% had an undetectable HIV
(HIV RNA suppressed 250/ will presumably require active HBV mended in the United States, consider-
µL) parameters; 2 participants were transcription for detection. Liver bi- ation of routine booster HAV vaccina-
women. As expected, plasma HCV RNA opsies from 5 HIV/HBV coinfected tion may be warranted for certain high-
showed a rapid and profound decline persons were studied using scLCD risk populations.
(-3 log10 copies/mL) over the first 24 and assays for HBV pregenomic RNA
hours followed by a slower decline over (pgRNA), cccDNA, and total HBV DNA Liver Inflammation,
the next 6 days (-0.2 log10 copies/mL). via digital droplet PCR. Three of the 5
Nonalcoholic Fatty Liver
Intrahepatic HCV RNA characteristics biopsies were obtained from persons
Disease, and Nonalcoholic
mirrored, or perhaps more accurately, on TDF-based ART and included 1 per-
Steatohepatitis
predicted plasma observations. Before son with an undetectable HBV DNA level.
therapy the percentage of HCV-infected In contrast to HCV, in the absence of In an observational AIDS Clinical Trials
hepatocytes was highly correlated with antiviral therapy, nearly all hepatocytes Group (ACTG) study analysis, one third
the baseline plasma viral load level (>95%) had evidence of HBV infection; of PLWH without viral hepatitis or heavy
(Spearman r, 0.9). Roughly 25% of he- in the setting of long-term TDF-based alcohol use had elevated aspartate
patocytes were infected before treat- therapy this decreased to around 30%. aminotransferase or ALT level on more
ment (range, 7.4-42.9%) with 8 IU of In the samples from persons with a HBV than one occasion. This transaminitis
HCV RNA per cell (IQR, 4-17). Inter- DNA level above 100 IU/mL in plasma, was associated with traditional risk fac-
estingly during therapy the number of HBV transcription, as assessed by HBV tors for nonalcoholic fatty liver disease
infected hepatocytes declined dramati- pgRNA, was present in nearly all cells (NALFD) (elevated triglyceride level,
cally (1% infected at day 7); however, analyzed. Conversely, when plasma HBV high blood pressure, female sex) and
the amount of HCV RNA per cell did DNA level was below 100 IU/mL, the had a higher hepatitis steatosis index
not change (12 IU/cell at day 7; IQR ratio of transcriptionally active cells suggesting NALFD, although imaging
5-27). A minority of cells at both time to total cells with cccDNA was below was not available to confirm fatty liver
points contained more than 100 IU/ 10 and significantly lower than sam- disease (Abstract 616)
cell. ples from non-suppressed persons. A Copenhagen observational cohort
Extrapolating intrahepatic HCV RNA Prolonged HBV suppression, in this case found a lower risk for computerized to-
expressing cell loss over the course of about 7 years, was associated with sub- mography-diagnosed fatty liver disease
therapy allowed the investigators to stantially less cccDNA per cell; 4% to (which could include alcohol-associated
estimate that all infected hepatocytes 5% of all hepatocytes analyzed in these disease as well as NAFLD) in PLWH than
would be gone or cleared between 5 2 samples still harbored HBV that was in matched controls without HIV (8.5%
and 8 weeks of therapy in this small transcriptionally silent (no pgRNA but vs 17.4%, respectively; PCROI 2019: Viral Hepatitis Volume 27 Issue 1 April 2019
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