The use of highly active antiretroviral therapy (HAART) has led to dramatic reductions in HIV-related morbidity and mortality in HIV-infected individuals [1–3]. However, parallel with this success has been the subsequent emergence of comorbidities, such as viral hepatitis. The hepatitis C virus (HCV) in particular, because of its high prevalence in HIV-positive populations (up to 90% in some [4–7]) and its greatly increased pathogenicity in the setting of HIV [6,8], is now a leading cause of death of HIV-positive individuals [9–11].
A number of reviews have recently been published regarding the care and treatment of HIV/HCV-coinfected persons [6,8,12]. These reviews have primarily focused on the treatment and management of HCV in HIV-coinfected individuals but have not generally examined issues related to HIV management in these patients. Unfortunately, a large proportion of people coinfected with HIV/HCV will never fully benefit from HCV therapy. Many individuals will not be able to access therapy, either because of contraindications to treatment, such as psychiatric comorbidity (including depression) or anemia, or because they are otherwise considered ineligible (e.g. are considered ‘non-responders’ to previous treatment, continue to use illicit drugs or alcohol, etc.). Of the individuals who do access treatment, recent data suggest that the probability of a sustained virologic response may be significantly less in HIV-coinfected individuals (40% overall in HIV-positive versus 55% in HIV-negative subjects; among those with HCV genotype 1, 29% in HIV-positive versus 45% in HIV-negative subjects [13–15]). Genotype 1 accounts for 70–75% of all HCV infections in the United States  and Canada  and is also predominant in HIV/HCV-coinfected populations [18,19]. HCV treatment effectiveness is limited by a number of factors including ineligibility for treatment, the prohibitory cost of growth factors to enable continued full-dose ribavirin, treatment guidelines that force people to abandon treatment by week 12 if their HCV RNA has not declined by a minimum of 2 log10 (log) copies/ml (in spite of evidence of altered HCV viral dynamics post-treatment in the presence of HIV [20,21]), the predominant prevalence of genotype 1, and the negative influence of HIV infection. Given the above limitations, HCV treatment can be expected to have a favorable impact on HCV-related morbidity and mortality in perhaps 20% of HIV/HCV-coinfected individuals [8,18,22]. Therefore, optimum HIV and antiretroviral drug therapy (ART) management are critical both for controlling HIV and for mitigating HCV.
Key ART-related questions of concern to clinicians and patients in the setting of HIV/HCV coinfection include the best time to initiate ART. Factors to consider are CD4 cell count, HIV viral load, hepatic inflammation and function, and the anticipated consequences of immune restoration in terms of autoinflammatory responses and elevation of HCV viral loads. Other important questions relate to the safety and tolerability of these agents in HIV/HCV-coinfected individuals, including liver enzyme elevations, as well as metabolic and mitochondrial toxicities, which are themselves linked to HCV infection.
The objectives of this review are, therefore, to summarize the available evidence regarding (a) the impact of HCV on the virologic and immunologic response to ART, including what is known regarding treatment interruptions; (b) the safety of ART agents in coinfected individuals; and (c) the relationship between immune suppression, immune restoration, and hepatic injury.
Computerized, English-language literature searches were carried out on MEDLINE and PubMed databases (January 1985 to May 2004) for studies in humans that examined HIV and HCV. Keywords for the search included HIV, AIDS, human immunodeficiency virus, acquired immune deficiency syndrome, HCV, HCV, hepatitis, immune deficiency, immune restoration, toxicity, diabetes, mitochondria, and metabolism. The bibliographies of selected articles were also searched for pertinent studies.
Impact of hepatitis C on the virologic and immunologic response to antiretroviral therapy
A number of studies have examined the impact of HCV on the virologic and immunologic response to ART. While most have found that there is no impact of HCV on the HIV virologic response to ART [11,23,24], there are mixed reports regarding immunologic response. Table 1 summarizes the conflicting evidence.
Greub et al.  defined an immunologic response to treatment as an increase in the CD4 cell count of at least 50 × 106 cells/l, and found that HIV/HCV coinfection was associated with a smaller CD4 cell recovery. Zala et al.  found that, while 86% of HCV-negative individuals had a CD4 cell count increase of ≥ 75 × 106 cells/l at 48 weeks, only 64% of HCV-positive individuals achieved this. Further, while it took a median of 17 weeks for HCV-negative individuals to achieve an increase of ≥ 75 × 106 cells/l, HCV-positive individuals took a median of 29 weeks. In a population-based cohort of previously treatment-naive individuals, these data were confirmed using mixed-effects models, showing that while HCV-negative individuals gained an average of 36 × 106 cells/l per year after adjustment for confounders, HIV/HCV-coinfected individuals lost, on average, 5 × 106 cells/l over a 12 month period . Although Klein et al.  found no difference in the mean CD4 cell count 24 months after initiation of ART, the HCV-positive individuals had a significantly reduced probability of achieving a CD4 cell count increase of ≥ 50 × 106 cells/l (hazard ratio 0.48; 95% confidence interval, 0.23–0.97; P = 0.04), after adjustment for baseline CD4 cell count, viral load, previous nucleoside drug experience, and duration of HIV infection. A number of reports have found no difference in CD4 cell count increase by HCV serostatus [23,24,27,28].
The lack of consistency in results regarding immunologic response among HIV/HCV-coinfected persons taking HAART may result from a number of factors. It can take up to 24 months of treatment for a complete CD4 cell count response to occur , beyond the time frame of many studies. How a CD4 cell count increase is defined is also another key factor (e.g., ‘time to’ CD4 cell count increase of 50 × 106 cells/l, versus time to an increase of 100 × 106 cells/l, versus using all intrasubject CD4 cell count measures), and most of the reports that found no difference in CD4 cell count response did not clearly define what actually constituted such a response. A third issue may be that a blunted response may mostly occur in those HIV/HCV-coinfected individuals with lower baseline CD4 cell counts. For example, in Klein's study  where no difference in mean CD4 cell count response was found, the baseline CD4 cell count was well above 200 × 106 cells/l among both HCV-positive and HCV-negative subjects, whereas the baseline HCV-positive CD4 cell count in Greub's landmark study was 172 × 106 cells/l . The lack of consistency may also result from inconsistencies in measures of, or accounting for, adherence to ART.
Injection drug use has been identified as an important predictor of treatment interruptions among HIV/HCV-coinfected persons [11,30,31]. However, the majority of injection drug users are coinfected with HCV. Therefore, it is difficult to know whether the reduced levels of adherence and increased rates of treatment discontinuation seen in this population result from lifestyle issues commonly associated with injection drug use or whether they are related to the increased toxicity experienced by many coinfected patients.
Only a few studies have examined HIV/HCV coinfection as an independent factor in switching or interrupting HAART [24,32,33]. Melvin et al.  reported ART discontinuation rates because of hepatotoxicity of more than twofold in HCV-coinfected individuals compared with those only infected with HIV. Among a population of 465 previously ART-naive individuals, HCV seropositivity was associated with an adjusted 40% increased risk of discontinuing or changing initial HAART regimens within the first year of treatment . The authors indicate that it was not clear whether this was a result of histological damage, reduced adherence, or increased hepatotoxicity, because hepatic cirrhosis was also independently associated with HAART discontinuation (adjusted odds ratio, 2.1; 95% confidence interval, 1.1–3.8) . Aceti et al.  reported that 83% of those who discontinued ART because of hepatotoxicity were HCV coinfected whereas D'Arminio Monforte et al.  found no impact of HCV on treatment interruptions caused by toxicity.
Safety of antiretroviral agents in HIV/HCV-coinfected individuals
ART agents are associated with a diverse array of short- and long-term toxicities, ranging in severity from benign to life threatening . There have been a number of reviews published addressing hepatotoxicity [34–36], but few that specifically focused on the role of HIV/HCV coinfection [8,36]. Although hepatotoxicity is most commonly defined as an increase in liver enzymes, there are several other types of liver-related toxicity that are both associated with ART and, independently, the result of HCV infection (Fig. 1). These include mitochondrial dysfunction, including peripheral neuropathy, metabolic changes, such as insulin resistance and diabetes mellitus, and hepatic steatosis. Consequently, the potential for overlapping pathology is significant among coinfected individuals receiving ART, and while these interactions have not been well characterized, some data are available and are described below.
Elevated liver enzymes
HCV in the absence of HIV infection independently causes elevated liver enzymes [15,37]. There is an emerging consensus that HCV infection increases the risk of developing elevated liver enzymes by two- to threefold in HIV/HCV-coinfected individuals receiving ART [38–41], and HCV accounts for the majority (> 75%) of severe hepatotoxicity in most studies (albeit that the prevalence of HCV coinfection in a geographical area will have an impact on this figure) [39,41–46] (Table 2). HIV/HCV-coinfected individuals may also be more likely to experience the clinical symptoms associated with highly elevated liver enzymes, such as malaise, asthenia, nausea/vomiting, fever, jaundice, and decompensation of previous ascites . Nunez et al.  found that most of their study participants who developed liver enzyme elevations experienced pure cytolysis (68/222) but five of the six participants who developed cytolysis and cholestasis were HCV positive.
It is notable that others have found little or no association between elevated liver enzymes and HCV among those coinfected with HIV [47–49]. A meta-analysis of this question would be helpful. Some of the relatively low rates of severely elevated alanine aminotransferase (ALT) may result from small study numbers  or selection bias . Recently, Becker  compared liver toxicity across several studies: the ATHENA (Amsterdam), Collaborations in HIV Outcomes Research US (CHORUS), the Italian Cohort of Naive for Antiretrovirals (ICONA), and Target. In spite of differences in the prevalence of viral hepatitis and definitions of hepatotoxicity across the cohorts, it was concluded that there was a low overall prevalence of hepatotoxicity in these cohorts (< 6.5%), but that in each cohort the risk of developing hepatotoxicity was associated with viral hepatitis, and in three of the four cohorts, also with an elevated baseline ALT. Although there was no consistent association found between hepatotoxicity and a particular drug or drug class, ritonavir and the recent use of nevirapine (during the first 12 weeks) were significantly associated with hepatotoxicity . Furthermore, female sex was independently associated with hepatotoxicity in the ATHENA cohort [34,50], while age over 60 years was a factor in the Target cohort . Also, HCV genotype 3 has been specifically associated with the development of acute liver enzyme elevations in HIV/HCV-coinfected populations [51,52]. This genotype is also strongly predictive of hepatic steatosis [53,54], underscoring the importance of knowing patients’ HCV genotype prior to initiating ART.
HIV/HCV-coinfected individuals are more susceptible to the hepatotoxicity associated with certain drugs, particularly nevirapine [29,34,39,40] and full-dose ritonavir [27,34,47,55]. An important and as yet unanswered question is whether small doses of ritonavir produce less hepatotoxicity than full-dose ritonavir, and whether even low doses should be avoided in HIV/HCV-coinfected individuals. In a small, retrospective analysis of HIV/HCV-coinfected participants enrolled in the Abbott 863 trial, comparing nelfinavir with lopinavir/ritonavir, there was a statistically significant increase in mean ALT levels in the nelfinavir but not the lopinavir/ritonavir arm at 24 weeks. By week 48, the mean ALT level was back to baseline in both groups . In contrast, Aceti et al.  found that saquinavir boosted with ritonavir, but not saquinavir alone, was associated with both overall and severe hepatotoxicity in coinfected patients. A recent Canadian study also found that independent predictors of grade 3/4 elevations in ALT among 202 HIV-positive subjects coinfected with hepatitis B virus (HBV) and/or HCV were older age and current use of lopinavir/ritonavir .
The pathogenesis of HCV is not fully understood  but is believed to be at least in part a result of intrahepatic mitochondrial damage [58–60]. Mitochondrial toxicity has also been widely associated with nucleoside analog use, particularly stavudine, didanosine, zidovudine and the combination of ribavirin plus didanosine [36,61–63].
Inhibition of mitochondrial DNA synthesis can lead to hyperlactatemia, lactic acidosis and even death [64–67]. It is now well established that using didanosine or stavudine simultaneously with ribavirin is contraindicated because of the risk of fatal lactic acidosis . Independent risk factors for the development of symptomatic lactic acidosis are HCV or HBV coinfection, being female, having liver disease, pregnancy, and obesity .
Mitochondrial damage is also associated with fatty liver [36,68] and is known to greatly accelerate fibrosis [36,69], particularly among people infected with HCV genotype 3 [53,54].
Although not life threatening, peripheral neuropathy is a painful and often progressive symptom with substantial impact on quality of life. This is a well-documented side effect of stavudine, didanosine, and zalcitabine ; it is attributed to nucleoside-induced mitochondrial toxicity . What is less known is that peripheral neuropathy is independently related to HCV infection, possibly through viral effects on mitochondria [71–73]. HCV infection is often associated with cryoglobulinaemia, and peripheral neuropathy is a comparatively common complication of cryoglobulinaemia associated with HCV infection and is thought to be attributable to nerve ischaemia . HCV RNA has been detected in nerve tissue, suggesting a possible direct role of HCV . A nerve conduction study showed abnormal findings in 77% of investigated HCV-positive patients .
Hepatic steatosis is linked to insulin resistance, which itself can be caused by both HIV protease inhibitors and HCV infection [36,64,69,74,75]. Duong et al.  found more insulin resistance in a group of 29 HIV/HCV-coinfected people compared with 76 controls infected only with HIV, but reported rates that were comparable to those in a group of 121 HCV-monoinfected controls. Of note, all the HIV-infected persons were taking HAART .
Similarly, HCV is linked with the development of type 2 diabetes mellitus [77–79]. In a large retrospective cohort of over 40 000 US HIV-positive veterans, HIV/HCV-coinfected individuals had a nearly twofold increased risk of developing diabetes mellitus, controlling for age, race, and history of drug/alcohol use . Mehta et al.  found that both HCV coinfection and protease inhibitor use were independently associated with developing hyperglycemia among 1230 individuals initiating ART, adjusting for age and baseline glucose level.
Liver fat content may be higher in those with lipodystrophy, although the relationship to HCV infection has not been examined . There is some evidence to suggest that HIV/HCV-coinfected patients may be more vulnerable to the symptoms associated with lipodystrophy syndrome, including lipoatrophy . For example, Duong et al.  observed more frequent lipoatrophy in HIV/HCV-coinfected patients (41% versus 14% in HIV-monoinfected patients; P = 0.003), and found that peripheral fat wasting was independently associated with HIV/HCV coinfection.
Surprisingly, a number of reports indicate that HIV/HCV-coinfected individuals have more favorable profiles in terms of total cholesterol, low density lipoprotein cholesterol, and triglyceride plasma levels, compared with HIV-monoinfected subjects [76,82,83]. The underlying mechanism remains unknown but may represent impaired synthesis of cholesterol in the liver .
In summary, there are several potential adverse interactions between antiretroviral toxicities and HCV infection. More research is needed to understand these interactions, to know whether their combined effects are additive or synergistic, to improve our understanding of the pathogenesis of HCV infection and the mechanisms of drug toxicities, and to optimize the clinical management of coinfected patients receiving ART. More research is also needed to determine the safety and tolerability of specific ART drugs including low doses of ritonavir in HIV/HCV-coinfected individuals, using either existing observational data or through clinical trials.
Immune suppression, immune restoration, and hepatic injury
The relationship between ART, immune suppression, immune restoration, and hepatic injury is complex and not well characterized.
With or without ART, low baseline CD4 cell count is strongly associated with progression of fibrosis, cirrhosis, and hepatocellular carcinoma among HIV/HCV-coinfected persons [84–87]. While most of these studies consider a ‘low’ CD4 cell count to be < 200 × 106 cells/l, Puoti et al.  found that the severity of liver fibrosis in chronic HCV infection was independently associated with a CD4 cell count of < 500 × 106 cells/l at time of biopsy, after controlling for HIV infection, age, duration of HCV infection, and alcohol abuse There are virtually no studies that contradict the finding that immunodeficiency is associated with the progression of hepatic disease.
Perhaps because of the role of ART in preserving functional immunity, a number of studies have found a favorable impact of ART in HIV/HCV-coinfected persons in terms of fibrosis/cirrhosis progression and liver-related mortality. Not using protease inhibitor therapy was strongly associated with faster progression to cirrhosis among 182 HIV/HCV-coinfected patients . It is important to note that these findings may be limited by a possible selection bias whereby those individuals with more advanced liver disease may have been less likely to have been prescribed protease inhibitors because of their known hepatotoxicity . Qurishi et al.  concluded that ART use significantly reduced long-term liver-related mortality among 285 HIV/HCV-coinfected patients. However, although the investigators showed decreasing rates of liver-related mortality between 1990 and 2002, their study population consisted predominantly of hemophiliacs infected during the early to mid-1980s. Therefore, it is likely that those patients surviving long enough to receive HAART had a higher probability of survival at the outset. A third study  concluded that ART did not influence the progression of fibrosis, but the study was cross-sectional, small (42), and based on only one biopsy, the timing of which was not clear.
Individuals who are more immunocompromised when they initiate HAART are at risk for experiencing immune reconstitution and inflammatory syndrome [29,92]. In 1999, the US Public Health Service/Infectious Diseases Society of American amended their HIV-guidelines to include HCV as an opportunistic pathogen among HIV-positive people. Chronic HCV is not the consequence of the direct destruction of hepatic cells by the virus. Rather, it results from an intermediate immune response that is large enough to induce hepatic cell destruction and fibrosis but not enough to eradicate the virus from its reservoirs . It is believed that hepatic injury resulting from immune recovery is the consequence of a similar mechanism . As the immune system recovers, the cytotoxic T cell response becomes more efficient at lysing infected hepatocytes, releasing HCV RNA from the hepatocytes killed and increasing plasma levels of HCV RNA . Increased lysis of infected hepatocytes upon immune reconstitution may also cause an increase in ALT levels . The increased HCV replication then further damages liver cells through apoptosis and other means such as cytokine disruption [88,94]. Hepatic fibrosis itself is a wound-healing response to ongoing liver injury , and HCV is considered an immune-mediated disease .
The potential for immune restoration to enhance liver disease progression is supported by data regarding both increased viral replication and fibrosis progression. Perhaps because of immune dysregulation, HIV/HCV-coinfected individuals have higher baseline HCV viral loads compared with those only infected with HCV [7,19,96,97] and, with one exception , ART initiation has been found to enhance significantly HCV replication [28,45,88,93,98–100].
Numerous studies [28,56,97] have found a relationship between baseline immune function, as measured by CD4 cell counts, and the magnitude of the increase in HCV RNA. In patients starting from a more immunocompromised state (baseline CD4 cell count < 350 × 106 cells/l), HCV RNA levels increased within the first 16 weeks following ART initiation and remained high throughout the 48 weeks of therapy that followed. In individuals with baseline CD4 cell count > 350 × 106 cells/l, significant increases in HCV RNA were found within the first 16 weeks, but these increases were transient and the HCV viral load returned to baseline levels within the following 16 week period . Sherman  found that only patients with a baseline CD4 cell count < 100 × 106 cells/l had significant increases in their HCV RNA (> 0.5 log copies/ml) at week 24 and 48.
There are several case series and reports in the literature regarding the impact of ART-related immune reconstitution on the development of hepatic fibrosis, cirrhosis, and end-stage liver disease [98,100–103]. Although this is a difficult question to study because of the need for repeat liver biopsies in patients prior to and following ART initiation, these reports suggest significant potential for severe hepatic deterioration parallel to an immune response among those individuals who are more immunocompromised on treatment initiation [101,103]. Benhamou et al.  found that a baseline CD4 cell count of < 200 × 106 cells/l was independently associated with a nearly threefold increase in the risk of developing cirrhosis following initiation of ART.
Elevated ALT/aspartate transaminase (AST) levels are common in HIV/HCV-coinfected individuals and may be related to the increased destruction of infected hepatocytes that accompanies immune restoration. Sulkowski et al. [39,105] found that a CD4 cell increase of > 50 × 106 cells/l was associated with severe hepatotoxicity (defined as a grade 3 or 4 change in AST/ALT). However, others have found only weak or no associations between baseline CD4 cell count, CD4 cell count recovery, and the development of elevated liver enzymes, in spite of high levels of the last among coinfected patients and evidence of other types of immune reconstitution syndrome [27,46,93].
While immune recovery may have deleterious consequences in many cases, it is noteworthy that there have been two case reports of spontaneous clearance of HCV RNA following HAART initiation, presumably related to immune reconstitution [7,106]. Younger age at time of HAART initiation (< 20 years of age) may improve the possibility of this outcome .
In spite of the widespread use of HAART, HCV is a leading cause of death among HIV-infected individuals [9–11]. The use of ART and the subsequent preservation of functional immunity may have protective effects in preventing or slowing the progression of hepatic injury, especially among those individuals who initiate treatment while their immune system is still intact. However, the data suggest that immune restoration stimulated by ART among those individuals with immunodeficiency may have a deleterious impact on the progression of HCV disease. The issue has not been well studied. However, current data indicate that those HIV/HCV-coinfected individuals who are not eligible for HCV treatment might consider initiating HAART at higher CD4 cell count levels than their HIV-monoinfected counterparts to mitigate the potential immune reconstitutive effects of ART, and to slow HCV disease progression by preserving functional immunity. Treating HCV early in both the HIV and HCV disease process may however have the dual beneficial effect of maximizing the chance of achieving a sustained HIV virologic response [8,13] and maximizing the benefits of future ART. More prospective research is needed to quantify the impact of ART-related immune restoration on progressive histologic hepatic injury and to elucidate the immune-mediated components of the two viruses combined. As there is also evidence that ART use is associated with HCV RNA replication in those with previously undetectable HCV RNA, and that the development of HCV antibodies follows ART initiation , patients should be tested for the presence of HCV RNA and antibodies before and after initiating treatment [101,107].
Currently available data convey two key messages related specifically to the use of ART in HIV/HCV-coinfected individuals: (a) that both immune suppression and restoration can contribute to the onset and acceleration of HCV-related liver disease; and (b) that the morbidity associated with HCV infection, such as insulin resistance, diabetes, mitochondrial dysfunction, and liver inflammation, are all also associated toxicities of ART, which together may be at least additive. Whether the apparent aggravation of liver injury and HCV disease progression among those coinfected with HIV results from immune restoration, ART-related hepatotoxicity, or enhanced HCV replication is not clear, although it is likely that interactions between the three occur. Specific recommendations based on the available evidence for the initiation and management of ART in HIV/HCV-coinfected individuals are summarized in Table 3.
HCV treatment has evolved to a degree where sustained virologic clearance is possible for some patients who are eligible for treatment, including up to 70% of those coinfected with HIV and with HCV genotypes 2/3, but for fewer than 30% of those coinfected with HIV and HCV genotype 1, the dominant genotype among HIV/HCV-coinfected populations [13,15]. Therefore, while HCV treatment should be considered for most HIV/HCV-coinfected individuals, only a relatively small proportion of them can expect to eliminate their HCV infection. If HCV treatment is not an option, then HIV treatment becomes central to the health management of such coinfected patients. Unfortunately, insufficient research has been conducted yet to indicate when the most appropriate time is to initiate ART in dually infected patients. Similarly, the relative effectiveness of various available regimens in HIV/HCV-coinfected patients is not fully established.
The data regarding baseline CD4 cell count, CD4 cell count response, and progression of hepatic injury, especially liver fibrosis/cirrhosis, are intriguing. Clearly this is an area that requires more prospective research to confirm the data to date and to elucidate the mechanisms by which immune deterioration and restoration are linked to the progression of fibrosis and cirrhosis. For example, if the pathogenetic mechanism of HCV is immunologic cytotoxicity, why do people with the lowest immunity have the worst hepatic disease? The 2002 International AIDS Society treatment guidelines indicate that HAART treatment in people with CD4 cell counts > 200 × 106 cells/l should be individualized, considering the rate of decline of the CD4 cell count, HIV viral load, patient interest and potential to adhere, and individual risks of toxicity and drug–drug interactions . The data presented in this review suggest that HCV status should also be considered a factor in that decision. This may be particularly important in men and in those who acquired HCV at a later age, since both are important predictors of liver fibrosis progression in HIV-coinfected individuals [19,89,108].
There is significant potential for overlap between HCV-attributable morbidity and ART-associated toxicity; clinical research to date suggests this is resulting in elevated rates of mitochondrial and metabolic adverse events. More research is needed to understand whether these interactions are additive or synergistic, to elucidate the pathogenesis of HCV infection, and to develop better clinical monitoring and responses to these emerging issues. Further research is also needed to clarify the role that this increased morbidity has on ART discontinuation, and its subsequent impact on mortality.
In conclusion, there are numerous burgeoning and maturing epidemics of HIV/HCV coinfection around the world and, if epidemiological coinfection projections are accurate, both HIV and HCV diseases can be expected to progress, in the absence of treatment, within 7 to 15 years following infection . A significant proportion of these individuals are current drug users and HCV treatment may never be an option for many. HIV treatment, however, is becoming ever more accessible to drug-using populations and others and may be the only treatment option available. This review suggests that managing the HIV aspects of HIV/HCV coinfection is a complex therapeutic domain, and one in which the ultimate outcome for patients is held in the balance.
The authors wish to thank the staff of the John Ruedy Immunodeficiency Clinic at St. Paul's Hospital in Vancouver, and the staff of the HIV/AIDS Drug Treatment Programme at the BC Center for Excellence in HIV/AIDS.
Sponsorship: The Michael Smith Foundation for Health Research (MSFHR) and the Canadian Institutes for Health Research (CIHR) funded Doctoral Fellowships for Paula Braitstein. Anita Palepu is supported by a CIHR New Investigator Award and a MSFHR Senior Scholar Award.
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