Chronic HBV and HCV infections are major etiological factors in 75–80 % of HCC cases worldwide. Universal HBV vaccination on newborns in Taiwan since 1985 has lead to a 70 % reduction in HBV-related HCC in young-aged children (Chang et al. 2009). Nevertheless, millions of individuals who had already chronically infected by HBV are still under the risk of developing HCC. Unfortunately, no effective vaccine is available for preventing HCV infection now. The proportion of HCV-related HCC has progressively increased, especially in the developed countries (El-Serag 2012). For these people persistently infected by either HBV or HCV, antiviral therapies’ target on HBV and HCV can be an effective strategy to reduce risk of HCC.

Treatment of HBV–HCV coinfection is important in endemic area because of its fairly high prevalence due to shared routes of transmission and increased risk for liver diseases, including HCC. Although no specific treatment guidelines are established, individualized therapy according to hepatitis virology, history of antiviral treatment, and stage and grade of liver disease is recommended (Potthoff et al. 2010).

Before initiation of therapy, determination of dominant virus infection is required. Combination of interferon/pegylated interferon and ribavirin are current choice of treatment for patients with dominant HCV infection. There were 43–69 % of treated patients who showed HCV-SVR at the end of 24 weeks of therapy with interferon plus ribavirin (Potthoff et al. 2010). After 24 or 48 weeks of combination therapy in genotype 2/3 HCV and genotype 1 HCV, respectively, high HCV-SVR rate can be achieved in both genotypes (83 % for genotype 2/3 and 72 % for genotype 1) (Liu et al. 2009). At the end of 24–48 weeks of follow-up, undetectability of HBV DNA was obtained in 11–18 % for interferon plus ribavirin and 56 % for pegylated interferon plus ribavirin (Liu et al. 2009; Potthoff et al. 2010). Interestingly, the combination therapy seemed to have higher chance of HBsAg clearance, which is the optimal treatment goal. The proportion of HBsAg clearance was 11–19 % for these two types of regimens (Liu et al. 2009; Yeh et al. 2011). However, as severe hepatic flares and recurrence of HBV after therapy have been reported, using this combination therapy with caution and long-term virological monitoring in some coinfected patients are necessary. In HBV-dominant or dually active HBV–HCV-coinfected patients, the optimal therapeutic regimen remains unestablished.

Coinfection of HBV–HIV and HCV–HIV usually hastens the development of liver diseases, including fibrosis and HCC. Generally speaking, monotherapy of interferons, pegylated interferons, lamivudine, adefovir, entecavir, and telbivudine has yielded much less satisfactory responses in HBV–HIV-coinfected patients (Lacombe and Rockstroh 2012). Nevertheless, tenofovir monotherapy offered some benefits, such as effective virological suppression, good resistance profile, and histological improvement. However, interruption use must be avoided because of viral breakthrough-induced deleterious consequences.

According to the guidelines proposed by the European AIDS Clinical Society (Lacombe and Rockstroh 2012; Soriano et al. 2010), HBV–HIV-coinfected patients who do not need HIV treatment (>500 CD4 + cells per uL) are suggested to receive early combination therapy of tenofovir and lamivudine/emtricitabine or to receive NUC therapy (either adefovir or telbivudine) in “early add-on” strategy when their HBV DNA level was more than 2,000 IU/mL. In this group of patients who have favorable response to interferon therapy, a 48-week course of interferon is suggested. When both HBV and HIV treatments must be applied, the appropriate option for treatment depends on prior use of lamivudine. In lamivudine-naïve patients, combination of tenofovir plus lamivudine/emtricitabine is the therapeutic option. And for lamivudine-treated patients, adding tenofovir, entecavir, or other HIV nucleos(t)ide reverse transcriptase inhibitors is recommended. Besides, lamivudine-containing HAART has been shown to be able to suppress HBV replication in HBeAg-negative HBV–HIV-coinfected patients (Fang et al. 2003). Although the above guidelines have been proposed, more solid evidence is still needed to make evidence-based therapeutic decisions.

In regard to treatment of HCV–HIV-coinfected patients, SVR rates could be achieved to 27–50 % by using treatment of pegylated interferon with ribavirin, which is the current standard therapy. Higher SVR (44–73 %) was observed in genotypes 2 and 3. In contrast, only 17–35 % genotype 1 and genotype 4 patients reached SVR (Lacombe and Rockstroh 2012).

Regimens for HCV–HIV-coinfected patients would be different according to HCV genotype and virological response. For non-HCV genotype 1 patients, in patients with rapid virological response (undetectable HCV viral load at week 4), 24 and 48 weeks of pegylated interferon/ribavirin combination therapy are recommended for genotype 2/3 and genotype 4, respectively. If the virological response is not achieved at week 12, treatment should be stopped. Patients with virological response at week 12 and undetectable HCV RNA at week 24 are recommended to receive 48- and 72-week courses of treatment for genotype 2/3 and genotype 4, respectively (Lacombe and Rockstroh 2012; Soriano et al. 2010). For HCV genotype 1 patients, longer duration of treatment may provide benefits under the conditions of early virological response at week 12 and undetectable virus at week 24. However, patients with higher fibrosis stages are recommended to have therapy of interferon/ribavirin combination plus HCV protease inhibitors. Recent pilot trials showed that this triple therapy in coinfected patients increased the SVR rate when compared with patients receiving combined treatment (Ingiliz and Rockstroh 2012). In addition, based on the results from clinical studies, HAART may offer positive impact on control of prognosis of liver damage in HCV–HIV-coinfected patients, and most of first-line HAART has good fitness in these patients (Jones and Nunez 2011).

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is a necessary factor for Kaposi’s sarcoma (KS), the most common malignancy in HIV patients who became immunocompromised. Elevated KSHV viral load was observed more frequently in KS patients than in asymptomatic KSHV-infected patients and was associated with a higher risk of AIDS-KS (Gantt and Casper 2011; Sunil et al. 2010). There is still no effective vaccine for KSHV. Nevertheless, several studies showed that anti-herpes virus drugs, such as ganciclovir and valganciclovir, not only reduced KSHV viral load but also prevented AIDS-KS (Gantt and Casper 2011). Though these small studies still need further confirmation (Gantt and Casper 2011), it will be interesting to examine the effects of these promising agents in combination with DNA synthesis blockers or lytic replication inducer in future clinical trials.

The replication of KSHV strongly depends on HIV-induced immunodeficiency (Mesri et al. 2010). Early use of highly active antiretroviral treatment (HAART) can restore host immunity and decrease the incidence and mortality of AIDS-KS in HAART-treated patients (Bower et al. 2006; Mesri et al. 2010). Compared with that in pre-HAART era, KS incidence in HAART era dropped by sixfold (Sunil et al. 2010). Even in resource-limited regions, early use of HAART can result in reduced KS incidence (Casper 2011). In the individual patient level, HAART is also significantly associated with control of KSHV viremia (Bourboulia et al. 2004). However, for late presenters who had already developed KS at the time of initial diagnosis, HAART alone induces complete remission in only half of these patients (Nguyen et al. 2008). For AIDS-KS patients, who did not reach complete remission with HAART alone, co-administration of HAART and chemotherapy could improve the response rate to 81.5 % (Bower et al. 2006). HAART can be classified to protease inhibitor (PI)-based and non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. No difference in KS incidence rate between these two types of regimens was observed in small observational studies (Gantt and Casper 2011), but PI-based HAART seemed to have better efficacy because more complete remission and relapse were reported when switching therapy from PI-based to NNRTI-based HAART (Gantt and Casper 2011). Nevertheless, whether PI-based HAART does have a therapeutic advantage for KSHV or not, this superiority still requires more convincing evidence to support, and controlled trials with large sample size and optimized HAART regimens are urgently needed.

For KS in HIV-negative patients, a 28-patient trial study showed that treatment with individual ART (indinavir) induced tumor regression and stabilization of disease progression in some patients (Monini et al. 2009). In addition to KS, KSHV was also linked to primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD) (Chang et al. 2006), which are rare malignancies with very poor prognosis. Recently, few studies proved that treatment with HAART alone or with other therapy (e.g., monoclonal antibodies) for PEL and MCD may prolong resolution of symptoms (Sunil et al. 2010).

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell lymphoma (ATL) (Poiesz et al. 1980). Although only a small proportion (<6 %) of 15–20 million estimated infected people worldwide developed ATL after a 10- to 40-year latent period (Proietti et al. 2005), the prognosis for ATL patients is very poor. Median survivals of acute and lymphomatous ATLs are less than one year (Goncalves et al. 2010).

Compared with asymptomatic carriers, ATL patients had significantly higher level of HTLV-1 proviral DNA and antibody titer (Manns et al. 1999). The quantity of HTLV-1 proviral DNA is a predictive factor for the development of ATL and is correlated with clinical outcomes (Etoh et al. 1999; Iwanaga et al. 2010; Okayama et al. 2004). Based on the accumulated data, antiviral therapy now is one of the treatment options for ATL (Tsukasaki et al. 2009). Treatment for ATL with antiviral drugs was investigated in the early 1980s in Japan, but encouraging improvement was obtained from two trials that combined interferon-α and zidovudine (AZT) in treating ATL patients reported in 1995 (Gill et al. 1995; Hermine et al. 1995). These two studies described impressive high response rate (more than 50 %) and mild toxic effects, and the survival time was prolonged to more than one year. After that, many small studies (all less than 30 patients) using interferon-α and AZT/zalcitabine were performed in France (Hermine et al. 2002), United Kingdom (Matutes et al. 2001), Martinique (French West Indies) (Besson et al. 2002), and United States (Ratner et al. 2009). Overall, these studies showed consistent efficacy of antiviral therapy. Recently, a worldwide meta-analysis with 254 ATL patients treated with interferon-α and AZT combination and/or with chemotherapy provided further evidence that combination of interferon-α and AZT treatment resulted in high response and significantly prolonged survival (Bazarbachi et al. 2010). However, the survival advantage was limited to acute, chronic, and smoldering subtypes. For lymphomatous ATL, chemotherapy seemed to be more effective than antiviral therapy. Besides, treatment with combination of interferon-α/AZT and arsenic trioxide also resulted in promising outcome on 7 patients with relapsed/refractory acute or lymphomatous ATL (Hermine et al. 2004). Another study using 10 chronic ATL patients showed 100 % response to the treatment (Kchour et al. 2009). Although these were preliminary observations, the feasibility of this regimen has been considered.