INTRODUCTION — The intersection of the HIV and hepatitis C virus (HCV) epidemics has significant clinical implications and raises many challenging issues for patients and their health care providers [1]. A thorough understanding of the natural history of liver disease in this complex patient population is critical for optimal management.
The epidemiology, natural history, and diagnosis of HCV in patients with HIV will be discussed here. Treatment of chronic HCV infection in patients with HIV is discussed elsewhere. (See "Treatment of chronic hepatitis C virus infection in the patient with HIV".)
VIROLOGY OF HCV
Viral kinetics — HIV (a retrovirus) and HCV (a flavivirus) are RNA viruses. The viral kinetics of HIV and HCV have been determined by perturbation of the steady state between virus production and clearance with potent antiviral agents [2,3]. HIV viral production rates approximate 10(10) virions a day with a half-life of less than six hours [2]. Virion production rates are even greater with HCV, approaching 10(12) virions a day with a virion half-life of 2.7 hours [3].
Viral load — During the chronic stage of either HIV or HCV infection, a relatively stable viral load or "set point" is maintained [4,5]. However, in the setting of combined infection, HCV RNA levels increase after HIV seroconversion and continue to increase over time compared with patients with HCV alone [6-8]. The level of HCV viremia is inversely correlated with CD4 counts in most, but not all studies [7,9] and may transiently increase with initiation of antiretroviral therapy (ART) or heavy alcohol use [10]. Overall increases in the HCV viral load do not have implications for the severity of liver-related disease.
One study evaluated whether higher levels of HCV viremia in patients with HIV may be related to immunosuppression [11]. The researchers reasoned that if high levels of replication were due to decreased immune selective pressure, then a reduced rate of nucleotide changes would be expected within the virus itself. However, in an investigation of HCV envelope sequences in 79 patients, with or without HIV coinfection, no significant divergence was demonstrated over time between the two groups. Another way HIV infection may increase HCV replication is through the virus itself; one in vitro study demonstrated that the envelope protein of HIV (gp120) increased HCV replication through engagement of cellular coreceptors of HIV (ie, CXCR4 or CCR5) [12].
Viral reservoirs — HIV replicates in many cell types in addition to CD4+ T-cells. It is controversial whether HCV replicates in extrahepatic sites, such as peripheral blood mononuclear cells (PBMCs) [13]. While some studies have documented HCV RNA-negative strands (the viral replicative intermediate) in PBMCs, others have not confirmed this finding [14,15]. Some have suggested that HCV RNA replication in PBMCs may occur in patients with HIV/HCV coinfection, but not in those with HCV alone [16].
The implications for patients with HIV are unclear, but in other chronic infections (eg, tuberculosis and cytomegalovirus), continuous activation of the immune system can lead to an increase in activated CD4+ T-cells, which are preferential targets of HIV [17,18]. HCV replication in PBMCs or dendritic cells could also be a mechanism for the relapse of HCV viremia that is seen in patients with HIV after treatment is discontinued [15].
HCV has also been isolated from cervicovaginal lavage fluid [19] in HIV-seropositive women, but not in women with HCV alone [20]. This may explain the higher rates of perinatal HCV transmission observed in the setting of coinfection. (See 'Epidemiology' below.)
Genetic heterogeneity — Single-stranded RNA viruses, like HIV and HCV, lack proofreading mechanisms, resulting in high mutational rates [21]. This leads to the formation of genetically distinct viral variants that collectively comprise a "quasispecies." Whether a particular nucleotide substitution results in a replication-competent mutant depends upon the involved site.
With HIV, it is estimated that all possible single-point mutations occur between 10(4) and 10(5) times per day in an infected individual [22]. This leads to a large pool of genetic variants able to adapt rapidly to changing selective drug pressures [23].
During replication of HCV, RNA-dependent RNA polymerase frequently introduces random nucleotide errors, resulting in a high rate of spontaneous nucleotide substitutions [24]. Like HIV, sequence heterogeneity is concentrated in certain regions, such as the first hypervariable region (HVR1) of the E2 gene, which encodes the envelope protein of HCV [25]. This is analogous to the hypervariable region in the V3 loop of gp120, the envelope protein of HIV [26]. Increased sequence variability of the E2 HVR of the HCV genome has been noted in individuals with HIV/HCV coinfection when compared with HCV-infected individuals [25].
These similarities between HIV and HCV viral diversity have treatment implications. The extent of the quasispecies evolution in an individual and the level of viremia have been implicated as predictors of response to interferon [25,27]. In one study of patients with HIV/HCV coinfection, lower quasispecies complexity of HCV was associated with earlier viral clearance in response to interferon-based regimens [28]. Furthermore, there is evidence of different evolution of the quasispecies of HCV in various compartments as has been noted for HIV [29].
The potential for HCV drug resistance parallels that of HIV, as demonstrated with the introduction of directly acting antiviral agents against HCV (eg, DAAs) [30]. As described in the past with HIV, resistance mutations to specific HCV protease and polymerase inhibitors have been identified even in treatment-naive patients with HCV monoinfection and HIV/HCV coinfection [31,32]. Resistance-associated substitutions and their impact on response to specific DAAs are discussed in detail elsewhere. (See "Direct-acting antivirals for the treatment of hepatitis C virus infection" and "Predictors of response to antiviral therapy for chronic hepatitis C virus infection", section on 'Resistance-associated substitutions'.)
EPIDEMIOLOGY — Coinfection with HIV and HCV is common since both infections share similar routes of transmission. In a meta-analysis of over 780 studies evaluating populations with HIV worldwide, the overall prevalence of HCV coinfection was estimated to be approximately 6 percent [33]. There was substantial geographic variation, with Eastern Europe and Central Asia estimated to account for 27 percent of the global population of individuals with coinfection. In the United States and Western Europe, studies have suggested that up to 30 percent of patients with HIV are also infected with HCV [34,35].
Because the relative efficiency of HCV transmission differs by route, the prevalence of coinfection varies markedly across risk groups, with much higher rates in people who inject drugs compared with those whose HIV exposure was through heterosexual sex. The sequence of infections also depends on transmission route. For example, injection drug users usually acquire HCV before HIV infection while men who have sex with men (MSM) typically acquire HIV before HCV infection [36,37].
Percutaneous exposure — HCV is transmitted efficiently via percutaneous routes, so seroprevalence rates are highest in injection drug users and hemophiliacs who received contaminated blood products prior to the introduction of HCV screening in 1990. Injection drug use is the leading route of HCV transmission in resource-rich settings, since the risk of post-transfusion HCV infection is now extremely low. Approximately 50 to 90 percent of drug users are infected with HCV after sharing contaminated needles or drug paraphernalia [38]. Globally, an estimated 80 percent of individuals with HIV and a history of injection drug use have evidence of HCV coinfection [33].
In the United States, increases in injection behaviors have resulted in rising incidence of HCV infection and more individuals at risk for HIV/HCV coinfection. In 2015, in and around Scott County, Indiana, an investigation of a cluster of HIV cases resulted in identification of 135 new diagnoses of HIV, with HCV coinfection present in 114 (84.4 percent), among a community of 4200 residents [39]. This outbreak was linked to injection of oxymorphone and lack of local harm prevention services. A separate cluster of 129 HIV cases associated with high rates of HCV was reported in Massachusetts in 2019, with 88 percent reporting injection drug use as a risk factor [40]. Contributing factors included local transition from heroin to intravenous fentanyl, homelessness, and incarceration. The opioid epidemic in North America may result in new cases of HIV/HCV coinfection. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'Injection drug use'.)
Heterosexual partners — Among heterosexual partners, HIV is much more easily transmissible than HCV via intercourse [41,42]. The risk of HCV transmission is exceedingly low in monogamous couples [43], but appears to increase in patients who report multiple sexual partners [38,44]. Globally, the prevalence of HCV coinfection is approximately 4 percent among individuals whose main HIV exposure risk was through heterosexual sex [33].
Whether underlying HIV infection increases the risk of heterosexual HCV transmission to an uninfected partner is unclear due to contradictory study results [45-47]. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'Sexual or household contact'.)
Men who have sex with men — The global prevalence of HCV/HIV coinfection among men who have sex with men (MSM) is estimated to be 6.4 percent, but this varies by geographic region [33]. The seroprevalence of HCV in MSM with HIV in the United States ranges from about 4 to 8 percent [48,49], which is similar to that found in HIV-uninfected MSM [50] but higher than that reported for the entire population (1.8 percent) [51]. In contrast, in a study of 689 MSM from the Netherlands, HCV prevalence was 0.4 percent among HIV-uninfected MSM and 18 percent among MSM with HIV [52]. Over the study period, HCV prevalence among MSM with HIV increased significantly (15 to 21 percent). Among a cohort of 3333 MSM with HIV, HCV incidence increased 18-fold from 1998 to 2011 [53].
Accumulating data from the United States and Europe suggest that an increased risk of HCV transmission exists among MSM whose predominant risk factor is unsafe sex [48,53-59]. Molecular methodology has been useful in identifying transmission clusters of HCV [58,60,61]. For example, phylogenetic analysis of genotype 4 HCV virus in 12 MSM with HIV found that 10 had an identical source of infection, which appeared to be sexually transmitted [60]. New HCV infections appear to be especially common among MSM with HIV; HCV transmission may be enhanced by mucosal injury and/or concomitant sexually transmitted diseases [44]. Among MSM, unprotected anal sex, fisting, group sex, and recreational drugs (eg, gamma hydroxy butyrate) [52] are associated with HCV acquisition [52,58,61-63]. The importance of mucosal damage as a risk factor for HCV acquisition was highlighted in a report in which 18 of 20 MSM reported either genital ulcerative disease (lymphogranuloma venereum, syphilis, or HSV-2) or fisting within the period of acute HCV seroconversion [55]. HCV is not as common among HIV-uninfected MSM. As an example, in a large cohort of MSM in the United States, HIV infection was associated with a six-fold increase in HCV incidence [64].
Perinatal transmission — Vertical transmission of HCV appears to be facilitated by HIV coinfection. A meta-analysis of 10 studies demonstrated that maternal coinfection increases the odds of vertical HCV transmission by approximately 90 percent (odds ratio, 1.9; 95% CI 1.4-2.7), compared with maternal HCV infection alone [65]. (See "Vertical transmission of hepatitis C virus".)
Health care workers — There are rare case reports of health care workers who have simultaneously acquired HIV and HCV via percutaneous exposure [66]. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers".)
PATHOGENESIS OF LIVER DISEASE — Patients with HIV/HCV coinfection have accelerated rates of fibrosis progression compared with patients with HCV alone. Insight into the mechanisms that underlie the immunopathogenesis of these persistent viral infections could lead to new therapeutic strategies [37].
Cellular immune responses — Liver fibrosis progression may be related to weak cellular immune responses to HCV antigens in patients with HIV. HIV infection is characterized by marked decreases in the number of circulating CD4 cells, functional impairment of both CD4 and CD8 cells, and down-regulation of CD28 expression, a costimulatory molecule required for effective lymphocyte activation [67]. Patients with low absolute CD4+ T-cell counts have a diminished frequency of HCV-specific CD8+ T-cell responses [68]. This observation provides a possible link between advanced immunosuppression and liver disease progression since CD8+ T-cell responses are thought to be of primary importance in the immune response to viral infection. Furthermore, successful antiretroviral therapy (ART) may restore cellular immune responses to HCV antigens [69].
HIV-associated immune activation — Another hypothesis suggests that chronic immune activation, secondary to HIV infection, influences liver disease progression through increased circulation of pro-inflammatory cytokines.
Chronic immune activation may be mediated by translocation of microbial products due to impaired gut mucosal integrity [70]. Disruption of mucosal barriers occurs in conjunction with severe CD4 depletion in gut-associated lymphoid tissue during early HIV infection. Translocation of microbial products is inferred by high circulating levels of serum lipopolysaccharide; in contrast, treatment with ART reduces LPS levels.
One study of patients with HIV/HCV coinfection found that CD4 lymphocyte depletion was strongly associated with markers of microbial translocation (eg, LPS, soluble CD14, and others); these markers were also associated with the development of cirrhosis [71]. The development of fibrosis may be related to Kupffer cell depletion, which is directly associated with CD4 T cell decline [72].
Activation of hepatic stellate cells — Activated hepatic stellate cells (HSCs) mediate collagen formation in hepatitis C virus (HCV)-related liver fibrosis. One study found that HSC activation levels were directly associated with CD4 and CD8 T cell immune activation and enhanced interleukin-15 (IL-15) gene expression, suggesting a pathogenic role for IL-15 in mediating liver fibrosis progression in patients with HIV/HCV coinfection [73].
HIV and apoptosis — Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates apoptosis in normal hepatocytes and is upregulated during HCV infection [74]. One in vitro study has suggested that glycoproteins of HIV (ie, gp120) may sensitize hepatocytes to cell death through upregulation of TRAIL-mediated apoptosis [75].
HCV-associated proinflammatory cytokines — HCV infection itself induces immunoregulatory and proinflammatory pathways that may contribute to progression of liver fibrosis [73]. These same proinflammatory cytokines may have a deleterious effect on HIV disease as well. (See 'Effect of HCV on the natural history of HIV' below.)
EFFECT OF HIV ON THE NATURAL HISTORY OF HCV — In patients with chronic HCV infection, concomitant HIV infection is associated with higher rates of morbidity and mortality related to liver disease [76,77]. Patients with HIV/HCV coinfection are less likely to clear viral infection, have more rapid rates of fibrosis, and have a higher risk of hepatic decompensation compared with patients with HCV monoinfection.
These cumulative observations led the United States Public Health Service to recommend that all patients with HIV undergo testing for HCV [78]. Treatment, with a sustained virologic response (SVR), may alter disease outcomes [79]. (See 'Screening for HCV infection' below.)
In addition, effective antiretroviral therapy (ART) of HIV among patients with coinfection is associated with better clinical outcomes, supporting early initiation of ART in this population. (See "When to initiate antiretroviral therapy in persons with HIV".)
Viral clearance — Patients with HIV have lower rates of spontaneous virologic clearance during acute infection, especially in the setting of lower CD4 cell counts, which in turn may be associated with impaired immune responses to HCV antigens [80-83].
Fibrosis progression rates — Patients with HCV and HIV coinfection have a relatively rapid rate of progression to cirrhosis, greater than that observed in most patients with HCV infection alone [84-87].
Studies of paired biopsy findings in patients with coinfection suggest that a high proportion have progressive fibrosis, even if minimal disease is detected at baseline. In a cohort of 282 patients with HIV/HCV coinfection without cirrhosis who underwent at least two liver biopsies as part of medical care, no or minimal fibrosis (METAVIR stage F0 or F1) was identified on the initial biopsy among 243 individuals (86 percent) [88]. With a median interval of 2.5 years between biopsies, progression of at least one METAVIR stage was observed in 34 percent, and progression of two or more stages was observed in 9 percent. These results are consistent with prior, smaller studies of patients with HIV/HCV coinfection with paired liver biopsies that suggested that 25 to 50 percent of patients had progression of fibrosis over a median of approximately three years [89,90]. Rapid progression to cirrhosis has also been reported among men with HIV who have sex with men who subsequently acquire HCV infection [87].
Such fibrosis progression rates are higher than those reported among patients with HCV monoinfection [91]. As an example, in a study of 122 patients with HIV/HCV coinfection and 122 patients with HCV monoinfection, matched for age, sex, alcohol use, age at HCV infection, and duration of HCV infection, the prevalence of extensive liver fibrosis on biopsy was greater among coinfected patients (54 versus 30 percent in patients with monoinfection) [84].
Noninvasive assessments of liver fibrosis can be performed more frequently than biopsy, and studies employing these techniques have also suggested more rapid progression of fibrosis with coinfection. In one study of HCV-infected injection drug users who underwent routine longitudinal liver elastography, participants with HIV infection had liver fibrosis measurements equivalent to those observed in HIV-uninfected participants who were almost a decade older [86]. (See "Noninvasive assessment of hepatic fibrosis: Overview of serologic and radiographic tests", section on 'Imaging tests'.)
However, not all studies have documented more severe liver fibrosis among patients with coinfection compared with those with monoinfection [92]. One possible explanation for these discrepant findings may be related to varying degrees of HIV-related immunosuppression in the patient populations.
Risk factors for progression — As in patients with HCV monoinfection, certain clinical characteristics, such as older age, alcohol use, diabetes, high body mass index (BMI), and elevated serum aspartate aminotransferase levels, have been associated with fibrosis progression among patients with HIV/HCV coinfection [84,86,89,90,93]. (See "Clinical manifestations and natural history of chronic hepatitis C virus infection", section on 'Factors associated with disease progression'.)
Steatosis (fatty liver) has also been associated with an increased risk of fibrosis progression among patients with both HCV monoinfection and HIV/HCV coinfection [94-96]. Moreover, steatosis appears to be more common in coinfected patients [95]. Steatosis among patients with HIV may be related to a variety of factors, including genotype 3 infection, ART, or metabolic factors, such as visceral obesity and insulin resistance [94,97].
HIV-associated factors that have been associated with fibrosis progression in most [84,86,90,93,98,99], but not all studies [88], include CD4 cell count <200 cells/microL, HIV viremia, and lack of ART.
Relationship of liver disease stage and clinical outcome — The risk of liver-related morbidity and mortality in an individual HCV-infected patient is an important consideration in management decisions. As in patients with monoinfection, this risk increases with the severity of liver fibrosis.
In a prospective cohort of 638 patients with coinfection (80 percent African-American), the risk of incident end-stage liver disease, hepatocellular carcinoma, or death was associated with the initial stage of fibrosis on liver biopsy evaluation [100]. Biopsies were scored for fibrosis stage according to the METAVIR system: F0, no fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis with few septa; F3, numerous septa without cirrhosis; and F4, cirrhosis. The following findings were noted:
●Compared with F0, the incidence rate ratio (IRR) was 2.31 for F2 (95% CI, 1.2-4.3); 3.2 for F3 (95% CI, 1.5-6.9); and 3.6 for F4 (95% CI, 2.1-6.2).
●Among the 226 patients who underwent HCV treatment, the incidence of clinical events in treatment nonresponders was not different from untreated patients. In contrast, no clinical events were observed in the 51 patients with SVR or relapse, including 19 with significant disease at baseline.
The actual risk of liver decompensation in the setting of fibrosis was assessed in a retrospective analysis of 892 patients with HIV/HCV coinfection with advanced fibrosis and a median follow-up of 5.4 years [101]. The rates of hepatic decompensation were 2.3 and 4.0 events per 100 person-years among those with advanced fibrosis determined by biopsy and transient elastography, respectively. The rates of decompensation were higher among those with cirrhosis (3.1 and 4 events per 100 person-years) compared to those with the equivalent of stage F3 disease (1.4 and 0.9 events per 100 person-years).
Hepatocellular carcinoma — Hepatocellular carcinoma (HCC) is an emerging complication in patients with HIV. Proportions of liver-related deaths among patients with HIV that were attributable to HCC increased from 15 to 25 percent in France from 2000 to 2005 [102]. Similarly, in a study from Spain, the incidence of HCC among patients with HIV increased from 0.1 to 1.1 cases per 1000 person years between 1999 and 2009 [103]. Almost all of the cases were associated with HCV coinfection. In a prospective, observational cohort in the United States, the incidence of liver cancer was eightfold higher in patients with HIV compared with the general population [104].
Data from the United States and Europe suggest that hepatocellular carcinoma (HCC) occurs at a younger age and is associated with shorter survival in patients with HIV/HCV coinfection compared with those with HCV infection alone [105,106]. In addition, a multicenter study in the United States and Canada also confirmed that progression from initial HCV infection to HCC was significantly faster in patients with coinfection (26 years) than in patients with HCV monoinfection (34 years) [107]. Whether HIV confers an independent risk factor to progression to HCC apart from a higher rate of fibrosis progression is unknown. Furthermore, it is possible that the effect of HIV has decreased in the modern ART era; one 2018 prospective study from France suggested similar rates of HCC and end-stage liver disease (ESLD) among patients with HCV monoinfection and patients with HIV/HCV coinfection [108].
Hepatic decompensation — Underlying HIV infection is also associated with a greater risk of liver decompensation among patients with HCV infection, even in the setting of ART [91].
As an example, a retrospective study of over 10,000 HCV-infected male US veterans evaluated the effect of HIV coinfection on the rate of hepatic decompensation, defined by the diagnosis of ascites, spontaneous bacterial peritonitis, or esophageal hemorrhage [109]. Decompensation was more frequent among the 4280 ART-treated patients with HIV/HCV coinfection than the 6079 patients with HCV monoinfection (6.3 versus 5.0 percent, adjusted HR 1.83, 95% CI 1.54-2.18). The estimated cumulative 10-year incidence of decompensation was 7.4 versus 4.8 percent for individuals with coinfection and those with monoinfection, respectively. Overall, among 34,119 adults with HIV in North America, the rate of ESLD remained constant between 2000 and 2015 [110].
Even though patients with HIV/HCV coinfection on ART appear to be at higher risk of liver decompensation compared with those without HIV, the risk is even greater in the absence of ART. In another study of over 10,000 male US veterans with HIV/HCV coinfection, with a median of three years of follow-up, 6.4 percent were diagnosed with hepatic decompensation (1.4 events per 100 person-years) [111]. The risk of decompensation was lower among the 6935 individuals who initiated ART compared with those who did not (HR 0.72, 95% CI 0.54-0.94). Ascites was the most frequent decompensation-defining event.
Other risk factors for hepatic decompensation among patients with HIV/HCV coinfection included baseline advanced fibrosis by noninvasive measures, baseline hemoglobin <10 g/dL, diabetes, untreated HBV infection, and poor CD4 cell increase following ART initiation [109,112-114]. (See 'Relationship of liver disease stage and clinical outcome' above.)
Mortality — Given the high rates of fibrosis progression and decompensated liver disease among HIV/HCV-coinfected patients, liver-related mortality is high among patients with HIV [76,77,91,115,116].
In a prospective observational international study of 23,441 patients with HIV who were followed for five years (Data Collection on Adverse Events of Anti-HIV drugs, the D:A:D Study), there were 1246 deaths; 14.5 percent were related to chronic viral hepatitis [77]. A strong association was found between mortality from liver disease and advanced immunosuppression. Similarly, in a study of 3990 patients with HIV from Denmark from 1995 to 2005, persons with HIV/HCV coinfection had considerably higher mortality rates than those who were HCV-uninfected (mortality rate, 59 versus 39 per 1000 person-years) [115]. Furthermore, the widening gap in mortality rates was even more significant in the late ART period from 2000 to 2005 (mortality rate, 57 per 1000 person-years versus 19 per 1000 person-years).
In one study, the median survival time after diagnosis of decompensated liver disease in patients with HIV/HCV coinfection ranged from only 13 to 16 months [117].
Effect of ART on HCV progression — Some [118], but not all studies [110,119], have suggested that the introduction of potent ART has been associated with a decline in liver-related mortality and slower rates of fibrosis progression. ART may slow down disease progression due to immune reconstitution [120].
In an observational study of 638 patients with HIV/HCV coinfection, 69 percent of whom were taking ART, viral suppression was associated with a lower risk of end-stage liver disease, hepatocellular carcinoma, and death [100]. Similarly, in a large retrospective study of over 10,000 men with HIV/HCV coinfection, ART use was associated with an approximately 28 percent lower likelihood of hepatic decompensation. (See 'Hepatic decompensation' above.)
Another study demonstrated that fibrosis progression rates were slower in patients who had achieved HIV viral load suppression on ART compared with those who still had detectable viremia on therapy, suggesting that HIV viral suppression is important as well [121]. A subsequent cross-sectional study also demonstrated that viral suppression on ART was associated with lower necroinflammatory activity on liver biopsy specimens while another retrospective study demonstrated that ART interruption was associated with an increased risk of fibrosis progression [122,123]. Despite improvements with ART, persons with HIV coinfection experience higher rates of fibrosis and, if cirrhotic, higher rates of liver decompensation compared with HIV negative HCV-infected controls [86,109]. (See 'Fibrosis progression rates' above and 'Hepatic decompensation' above.)
Early initiation of ART in patients with HIV is associated with an overall decrease in AIDS and non-AIDS related morbidity and mortality. This approach may be especially relevant for patients with HIV/HCV coinfection, particularly in those who are unable or unwilling to take HCV antiviral therapy [124]. This issue is discussed in detail elsewhere. (See "When to initiate antiretroviral therapy in persons with HIV".)
There are conflicting data as to whether any particular drug or class of antiretrovirals affect liver fibrosis progression rates [125,126].
EFFECT OF HCV ON THE NATURAL HISTORY OF HIV
HIV progression — There are conflicting results as to whether HCV infection does [7,127-130] or does not [131,132] have a deleterious effect on the course of HIV infection.
The following examples illustrate the range of findings in the largest reports:
●In a prospective cohort study of 1955 patients, no difference was detected in the risk of acquiring an AIDS-defining illness (ADI) or the risk of death when comparing HCV-infected or HCV-uninfected patients [131]. The findings were not affected by whether or not the patient was treated with antiretroviral therapy (ART).
●By contrast, in a study of 3111 antiretroviral-naïve patients who initiated ART, HCV seropositivity was an independent risk factor for progression to a new AIDS-defining clinical event or to death [121].
●Increased mortality was also seen in a retrospective study of 5914 patients with HIV, 37 percent of whom were HCV-positive [130]. Compared with the general population, the standardized mortality ratio (SMR) was 11.5 for HCV-positive patients, and 2.4 for HCV-negative patients. Among the patients with HCV coinfection and AIDS, the SMR was 20.8, compared with 4.8 for those with AIDS who were HCV-negative.
●In another retrospective study of 5397 patients with HIV (half of whom were HCV-seropositive), the incidence of new ADIs was significantly higher in the HCV-seropositive group compared with the HCV-seronegative group (adjusted relative risk [ARR], 2.61; 95% CI 1.88-3.61). The rate of mycotic infection, bacterial infection, toxoplasmosis, and HIV-related ADIs among patients with cirrhosis were significantly higher than HCV-infected patients without cirrhosis and patients with HIV alone [133].
●In a multicenter cohort of 9164 patients with HIV whose date of HIV seroconversion was known, evidence of HCV infection (positive antibody or RNA) was independently associated with an increase in AIDS-related mortality (adjusted HR 2.43, 95% CI 1.14-5.20) [134]. This association persisted across groups with varying HIV risk factors (eg, injection drug use, heterosexual, MSM, hemophilia).
The factors responsible for these disparate findings are not well understood, although one factor may be HCV viral load [7,129,135,136]. Two studies have demonstrated a relationship between higher HCV RNA levels and increased risk of clinical progression to AIDS and AIDS-related mortality [7,137]. HCV replication may result in generalized immune activation, which is associated with shorter survival in patients with HIV [137,138]. One study also demonstrated that the rate of CD4 cell gains was lower among patients who had chronic HCV infection compared with those who had spontaneously cleared their viremia [139]. Immune activation, with subsequent T-cell apoptosis, could also explain the observation that CD4+ gains after antiretroviral therapy (ART) initiation are generally lower in patients with coinfection compared with those with HIV alone [121]. In addition, two observational studies have suggested that discordance between absolute CD4 cell counts and CD4 T-cell percentages may be seen in patients with advanced liver disease, which may be related to splenic sequestration [140,141]. (See 'HIV-associated immune activation' above and "Techniques and interpretation of measurement of the CD4 cell count in people with HIV".)
Other comorbidities — Those with HCV/HIV coinfection may experience greater rates of nonhepatic complications compared with patients with HIV who are HCV uninfected. Such complications include osteoporosis or bone fractures [142,143] and chronic kidney disease [142-145]. Whether HCV confers additional cardiovascular risk or is associated with neurocognitive decline in patients with HIV remains unclear [146-150]. (See "Bone and calcium disorders in patients with HIV", section on 'Hepatitis C infection' and "Overview of kidney disease in patients with HIV", section on 'Glomerulonephritis due to hepatitis C virus coinfection' and "Epidemiology of cardiovascular disease and risk factors in patients with HIV", section on 'Hepatitis C virus infection' and "HIV-associated neurocognitive disorders: Epidemiology, clinical manifestations, and diagnosis", section on 'Comorbidities'.)
SCREENING FOR HCV INFECTION
Chronic infection — All persons with HIV should be screened for HCV infection using enzyme immunoassays; those with antibody to HCV should have quantitative HCV RNA testing, which confirms the presence of viremia and serves as a baseline prior to therapy [151]. These recommendations also apply to patients with persistently normal aminotransferases, since patients can have advanced fibrosis despite these laboratory findings [152]. (See "Screening and diagnosis of chronic hepatitis C virus infection".)
The sensitivity and specificity of third generation ELISA assays approach 99 percent [151]. However, patients with severe immunosuppression (eg, CD4 cell counts <100 cells/microL) may have a false negative serology due to impaired antibody formation; however, this occurs in than less than 5 percent of patients [153,154]. Thus, any HCV-seronegative patient with HIV who has significant risk factors for HCV acquisition (eg, injection drug use), or has unexplained abnormal aminotransferases should be screened further with hepatitis C RNA testing [155].
Patients with HIV infection are more likely to have HCV viremia compared with those without HIV infection. In two studies, for example, 91 percent of patients with coinfection had HCV viremia compared with approximately 75 percent of those with HCV alone. A possible explanation is that clearance of HCV is less likely to occur in patients with underlying HIV [7,156].
Acute HCV infection — In patients with suspected acute HCV infection, an HCV antibody and HCV RNA level should both be obtained since viremia precedes seroconversion. HCV antibody is detected approximately 8 to 12 weeks after infection although delayed antibody responses have been described in one small study of 43 patients with HIV [157,158]. In one study of men with HIV who have sex with men and who underwent systematic HCV testing in Switzerland, 14 percent of the patients with HCV viremia were negative for HCV antibodies [59]. Yearly antibody screening of sexually active patients with HIV is an additional strategy to capture incident cases [159,160]. (See "Clinical manifestations, diagnosis, and treatment of acute hepatitis C virus infection in adults".)
Screening for other hepatitis viruses — All patients with HIV should also be screened for past exposure to other hepatitis viruses (eg, hepatitis A IgG antibody and hepatitis B surface antigen and surface antibody). Immunizations for hepatitis A and hepatitis B are recommended if the patient is not immune [161-163]. (See "Prevention of hepatitis B virus infection in adults with HIV" and "Immunizations in patients with HIV", section on 'Hepatitis A vaccine'.)
HCV AND RISK OF HEPATOTOXICITY WITH ART — Chronic viral hepatitis increases the risk of hepatotoxicity from antiretroviral therapy [164-173]. Some have suggested that hepatitis C is associated with an increased risk of hepatotoxicity for all ART regimens [174,175], while others found an increased risk only with certain antiretroviral agents, such as ritonavir or nevirapine [164,165,176].
Although hepatotoxicity is more common in patients with chronic viral hepatitis, the clear benefit of antiretroviral therapy outweighs the risk of liver injury. Studies also support the positive impact of antiretroviral treatment on the progression of hepatic fibrosis in patients with HIV/HCV coinfection [118]. (See 'Effect of ART on HCV progression' above.)
When patients with concomitant HCV are initiated on ART, close laboratory follow-up is prudent and patients should be educated about symptoms that may suggest liver injury such as jaundice or darkening of urine, right upper quadrant pain, nausea, anorexia, pruritus and fatigue.
The pathogenesis of ART-associated hepatotoxicity may be related to immune reconstitution, which leads to hepatocyte necrosis [172]. Supporting this hypothesis is the observation that hepatotoxicity correlated with a rise in CD4 count in some reports [171,172]. However, an increase in the CD4 count may simply be a marker of a patient who is adherent with their medications and therefore at higher risk of drug injury compared with the patient who is not taking their medications at all.
The treatment of hepatitis C in patients with HIV is discussed separately. (See "Treatment of chronic hepatitis C virus infection in the patient with HIV".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hepatitis C virus infection".)
SUMMARY AND RECOMMENDATIONS
●During the chronic stage of both HIV and HCV, a relatively stable viral load or "set point" is maintained over long periods of time. However, in the setting of HIV, HCV RNA levels increase after HIV seroconversion and continue to increase over time. (See 'Virology of HCV' above.)
●Coinfection with HIV and HCV is common since both infections share similar routes of transmission. Prevalence rates vary by primary route of transmission. (See 'Epidemiology' above.)
●Patients with HIV/HCV coinfection have accelerated rates of fibrosis progression compared with patients with HCV alone, which may be related to HIV-associated immune activation, CD4 T cell depletion or immunodysregulation with production of proinflammatory cytokines. (See 'Pathogenesis of liver disease' above.)
●In patients with chronic HCV infection, concomitant HIV infection is associated with higher rates of morbidity and mortality related to end-stage liver disease. (See 'Effect of HIV on the natural history of HCV' above.)
●There are conflicting studies as to whether HCV affects the clinical progression of HIV disease. (See 'Effect of HCV on the natural history of HIV' above.)
●All persons should be evaluated for chronic HCV infection using a third generation enzyme immunoassay. Patients who are found to be HCV seropositive should undergo quantitative HCV RNA testing in order to confirm the presence of viremia. Patients who are found to be HCV seronegative should undergo HCV RNA testing if they have advanced immunosuppression (eg, CD4 counts <100 cells/mm3), risk factors for HCV acquisition, or elevated aminotransferases. (See 'Screening for HCV infection' above.)
●Chronic viral hepatitis increases the risk of hepatotoxicity from antiretroviral therapy. Patients should be counseled regarding the symptoms and signs of drug-induced liver injury prior to starting antiretroviral therapy. (See 'HCV and risk of hepatotoxicity with ART' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dr. Barbara McGovern, who contributed to an earlier version of this topic review.
1 : Hepatitis C in the HIV-infected patient.
2 : Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.
3 : Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.
4 : High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.
5 : Fluctuations in viral load (HCV RNA) are relatively insignificant in untreated patients with chronic HCV infection.
6 : Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users.
7 : Relation between HIV-1 and hepatitis C viral load in patients with hemophilia.
8 : High serum HCV RNA in chronic hepatitis C patients coinfected with HIV despite successful antiretroviral therapy.
9 : Effect of human immunodeficiency virus infection on hepatitis C virus infection in hemophiliacs.
10 : Effect of alcohol use and highly active antiretroviral therapy on plasma levels of hepatitis C virus (HCV) in patients coinfected with HIV and HCV.
11 : Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.
12 : HIV increases HCV replication in a TGF-beta1-dependent manner.
13 : Extrahepatic replication of HCV: insights into clinical manifestations and biological consequences.
14 : Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR.
15 : Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons.
16 : Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: evidence of active replication in monocytes/macrophages and lymphocytes.
17 : Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation.
18 : Why should hepatitis C affect immune reconstitution in HIV-1-infected patients?
19 : Possible compartmentalization of hepatitis C viral replication in the genital tract of HIV-1-coinfected women.
20 : Presence of hepatitis C virus (HCV) RNA in the genital tracts of HCV/HIV-1-coinfected women.
21 : RNA virus populations as quasispecies.
22 : HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.
23 : Viral dynamics of HIV: implications for drug development and therapeutic strategies.
24 : Hepatitis C virus genotypes and quasispecies.
25 : Hepatitis C in human immunodeficiency virus-coinfected patients: increased variability in the hypervariable envelope coding domain.
26 : Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop.
27 : Quasispecies nature of hepatitis C virus and response to alpha interferon: significance as a predictor of direct response to interferon.
28 : Hepatitis C virus (HCV) quasispecies complexity and selection in HCV/HIV-coinfected subjects treated with interferon-based regimens.
29 : Compartmentalization of hepatitis C virus (HCV) during HCV/HIV coinfection.
30 : Avoiding therapeutic pitfalls: the rational use of specifically targeted agents against hepatitis C infection.
31 : Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients.
32 : Hepatitis C virus drug resistance and immune-driven adaptations: relevance to new antiviral therapy.
33 : Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis.
34 : Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival.
35 : Human Immunodeficiency Virus/Hepatitis C Virus Coinfection in Spain: Prevalence and Patient Characteristics.
36 : Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses.
37 : Coinfection with HIV-1 and HCV--a one-two punch.
38 : Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection.
39 : Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorphone--Indiana, 2015.
40 : Notes from the Field: HIV Diagnoses Among Persons Who Inject Drugs - Northeastern Massachusetts, 2015-2018.
41 : Sexual transmission of hepatitis C virus among patients attending sexually transmitted diseases clinics in Baltimore--an analysis of 309 sex partnerships.
42 : Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group.
43 : Risk factors for hepatitis C virus seropositivity in heterosexual couples.
44 : Is sexual contact a major mode of hepatitis C virus transmission?
45 : Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV).
46 : Heterosexual transmission of hepatitis C virus and the possible role of coexistent human immunodeficiency virus infection in the index case. A multicentre study of 423 pairings.
47 : Absence of hepatitis C virus transmission but frequent transmission of HIV-1 from sexual contact with doubly-infected individuals.
48 : Prevalent and incident hepatitis C virus infection among HIV-infected men who have sex with men engaged in primary care in a Boston community health center.
49 : Hepatitis C prevalence among HIV-positive MSM in San Francisco: 2004 and 2008.
50 : Comparison of risk factors for hepatitis C and hepatitis B virus infection in homosexual men.
51 : The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.
52 : Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic.
53 : Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic.
54 : Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.
55 : Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission.
56 : Unsafe sex and increased incidence of hepatitis C virus infection among HIV-infected men who have sex with men: the Swiss HIV Cohort Study.
57 : Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV-infected men: a prospective cohort study.
58 : Sexual transmission of hepatitis C virus among HIV-infected men who have sex with men--New York City, 2005-2010.
59 : High Number of Potential Transmitters Revealed in a Population-based Systematic Hepatitis C Virus RNA Screening Among Human Immunodeficiency Virus-infected Men Who Have Sex With Men.
60 : Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy.
61 : Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours.
62 : A cluster of acute hepatitis C virus infection among men who have sex with men--results from contact tracing and public health implications.
63 : Risk Factors for Sexual Transmission of Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: A Case-Control Study.
64 : Incident hepatitis C virus infection in men who have sex with men: a prospective cohort analysis, 1984-2011.
65 : Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis.
66 : Simultaneous transmission of human immunodeficiency virus and hepatitis C virus from a needle-stick injury.
67 : HIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells.
68 : The magnitude and breadth of hepatitis C virus-specific CD8+ T cells depend on absolute CD4+ T-cell count in individuals coinfected with HIV-1.
69 : Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy.
70 : Microbial translocation is a cause of systemic immune activation in chronic HIV infection.
71 : Human immunodeficiency virus-related microbial translocation and progression of hepatitis C.
72 : Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution.
73 : Association of interleukin-15-induced peripheral immune activation with hepatic stellate cell activation in persons coinfected with hepatitis C virus and HIV.
74 : Increased hepatotoxicity of tumor necrosis factor-related apoptosis-inducing ligand in diseased human liver.
75 : HIV induces TRAIL sensitivity in hepatocytes.
76 : Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection.
77 : Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study.
78 : Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study.
79 : Sustained virological response to interferon plus ribavirin reduces non-liver-related mortality in patients coinfected with HIV and Hepatitis C virus.
80 : Impact of HIV on host-virus interactions during early hepatitis C virus infection.
81 : Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection.
82 : Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men.
83 : Assessing hepatitis C spontaneous clearance and understanding associated factors-A systematic review and meta-analysis.
84 : Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group.
85 : Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection.
86 : HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study.
87 : Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection.
88 : Fibrosis progression in human immunodeficiency virus/hepatitis C virus coinfected adults: prospective analysis of 435 liver biopsy pairs.
89 : Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults.
90 : Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus.
91 : Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis.
92 : The clinical spectrum of hepatitis C virus in HIV coinfection.
93 : Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus.
94 : Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients.
95 : Impact of human immunodeficiency virus infection on the prevalence and severity of steatosis in patients with chronic hepatitis C virus infection.
96 : Steatohepatitis: Risk factors and impact on disease severity in human immunodeficiency virus/hepatitis C virus coinfection.
97 : Hepatic steatosis and steatohepatitis in human immunodeficiency virus/hepatitis C virus-coinfected patients.
98 : Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis.
99 : Progression of liver fibrosis following acute hepatitis C virus infection in HIV-positive MSM.
100 : Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV.
101 : Risk of liver decompensation among HIV/hepatitis C virus-coinfected individuals with advanced fibrosis: implications for the timing of therapy.
102 : Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalité2005 study.
103 : Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain.
104 : Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003.
105 : Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome.
106 : The effect of HIV viral control on the incidence of hepatocellular carcinoma in veterans with hepatitis C and HIV coinfection.
107 : Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study.
108 : Human Immunodeficiency Virus/Hepatitis C Virus (HCV) Co-infected Patients With Cirrhosis Are No Longer at Higher Risk for Hepatocellular Carcinoma or End-Stage Liver Disease as Compared to HCV Mono-infected Patients.
109 : Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study.
110 : Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras.
111 : Antiretroviral therapy reduces the rate of hepatic decompensation among HIV- and hepatitis C virus-coinfected veterans.
112 : Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy.
113 : Natural history of compensated hepatitis C virus-related cirrhosis in HIV-infected patients.
114 : Hepatic decompensation in patients with HIV/Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV) triple infection versus HIV/HCV coinfection and the effect of anti-HBV nucleos(t)ide therapy.
115 : Survival of persons with and without HIV infection in Denmark, 1995-2005.
116 : Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression.
117 : Survival and prognostic factors of HIV-infected patients with HCV-related end-stage liver disease.
118 : Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy.
119 : Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis.
120 : Hepatitis C virus coinfection increases mortality in HIV-infected patients in the highly active antiretroviral therapy era: data from the HIV Atlanta VA Cohort Study.
121 : Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study.
122 : HAART is associated with lower hepatic necroinflammatory activity in HIV-hepatitis C virus-coinfected patients with CD4 cell count of more than 350 cells/microl at the time of liver biopsy.
123 : Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-hepatitis C virus co-infection.
124 : Early initiation of antiretroviral therapy: the current best way to reduce liver-related deaths in HIV/hepatitis C virus-coinfected patients.
125 : Association between exposure to nevirapine and reduced liver fibrosis progression in patients with HIV and hepatitis C virus coinfection.
126 : Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine.
127 : Effect of hepatitis C virus (HCV) genotype on HCV and HIV-1 disease.
128 : Hepatitis C virus load is associated with human immunodeficiency virus type 1 disease progression in hemophiliacs.
129 : Influence of coinfection with hepatitis C virus on morbidity and mortality due to human immunodeficiency virus infection in the era of highly active antiretroviral therapy.
130 : All-cause and liver-related mortality in HIV positive subjects compared to the general population: differences by HCV co-infection.
131 : Hepatitis C and progression of HIV disease.
132 : Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy.
133 : Coinfection with hepatitis C virus and HIV: more than double trouble.
134 : Effect of HCV infection on cause-specific mortality after HIV seroconversion, before and after 1997.
135 : Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections.
136 : Coinfection of hepatitis C virus with human immunodeficiency virus and progression to AIDS. Italian Seroconversion Study.
137 : Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus.
138 : Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage.
139 : Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-HCV coinfection before and after antiretroviral therapy.
140 : Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus.
141 : Discordance between CD4+ T-lymphocyte counts and percentages in HIV-infected persons with liver fibrosis.
142 : Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis.
143 : The effect of HIV-hepatitis C co-infection on bone mineral density and fracture: a meta-analysis.
144 : Hepatitis C viremia and the risk of chronic kidney disease in HIV-infected individuals.
145 : Hepatitis C Infection and the Risk of Non-Liver-Related Morbidity and Mortality in HIV-Infected Persons in the Swiss HIV Cohort Study.
146 : Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population.
147 : Atherosclerosis risk in HIV-infected patients: the influence of hepatitis C virus co-infection.
148 : Evaluation of endothelial function and subclinical atherosclerosis in association with hepatitis C virus in HIV-infected patients: a cross-sectional study.
149 : The risk of incident coronary heart disease among veterans with and without HIV and hepatitis C.
150 : HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study.
151 : Diagnosis, management, and treatment of hepatitis C.
152 : Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis.
153 : Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus.
154 : Screening for hepatitis C virus in human immunodeficiency virus-infected individuals.
155 : Factors associated with seronegative chronic hepatitis C virus infection in HIV infection.
156 : Protection against persistence of hepatitis C.
157 : Diagnosis, management, and treatment of hepatitis C: an update.
158 : Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV.
159 : Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America.
160 : Cost-effective screening for acute hepatitis C virus infection in HIV-infected men who have sex with men.
161 : Hepatitis A and B immunizations of individuals infected with human immunodeficiency virus.
162 : BHIVA guidelines on HIV and chronic hepatitis: coinfection with HIV and hepatitis C virus infection (2005).
163 : Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients.
164 : Incidence of adverse reactions in HIV patients treated with protease inhibitors: a cohort study. Coordinamento Italiano Studio Allergia e Infezione da HIV (CISAI) Group.
165 : Hepatotoxicity associated with antiretroviral therapy containing dual versus single protease inhibitors in individuals coinfected with hepatitis C virus and human immunodeficiency virus.
166 : Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection.
167 : Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy.
168 : Grade 4 events are as important as AIDS events in the era of HAART.
169 : Enhancement of hepatitis C virus replication and liver damage in HIV-coinfected patients on antiretroviral combination therapy.
170 : Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome.
171 : Longitudinal effect of antiretroviral therapy on markers of hepatic toxicity: impact of hepatitis C coinfection.
172 : Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996-1998. Groupe dEpidémiologie Clinique de Sida en Aquitaine (GECSA).
173 : Predictors of antiretroviral-related hepatotoxicity in the adult AIDS Clinical Trial Group (1989-1999).
174 : Impact of antiretroviral treatment on progression of hepatic fibrosis in HIV/hepatitis C virus co-infected patients.
175 : Hepatitis C virus-associated hepatitis following treatment of HIV-infected patients with HIV protease inhibitors: an immune restoration disease?
176 : Low risk of liver toxicity using the most recently approved antiretroviral agents but still increased in HIV-hepatitis C virus coinfected patients.
