Research Article: Challenges in Providing Treatment and Care for Viral Hepatitis among Individuals Co-Infected with HIV in Resource-Limited Settings

Date Published: March 26, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Wirach Maek-a-Nantawat, Anchalee Avihingsanon, Pirapon June Ohata.


Hepatitis B and C infections are prevalent among HIV-infected individuals with different epidemiologic profiles, modes of transmission, natural histories, and treatments. Southeast Asian countries are classified as “highly prevalent zones,” with a rate of hepatitis B and C coinfection in people living with HIV/AIDS of approximately 3.2–11%. Majority of hepatitis B coinfection is of genotype C. Most of the patients infected with hepatitis C in Thailand have genotype 3 which is significantly related to intravenous drug use whereas, in Vietnam, it is genotype 6. The options for antiretroviral drugs are limited and rely on global funds and research facilities. Only HBV treatment is available for free through the national health scheme. Screening tests for HBV and HCV prior to commencing antiretroviral treatment are low. Insufficient concern on hepatitis-virus-related liver malignancy and long-term hepatic morbidities is noted. Cost-effective HCV treatment can be incorporated into the national health program for those who need it by utilizing data obtained from clinical research studies. For example, patients infected with HCV genotype 2/3 with a certain IL-28B polymorphism can be treated with a shorter course of interferon and ribavirin which can also help reduce costs.

Partial Text

Most countries in Southeast Asia currently have limited resources in providing universal coverage for HIV treatment and care. Since the start of the global AIDS epidemic, Thailand has become the only country within this region with a high prevalence of HIV infection (>1%). In 2009, the HIV prevalence has decreased to 2.3 million because of the HIV prevention campaigns. These HIV prevention campaigns focused on promoting the use of condoms among commercial sex workers and their clients which achieved >90–95% success in preventing HIV transmission. Another campaign known as the prevention of mother-to-child transmission (PMTCT) was also successful. However, in recent years, the rates of new HIV infection have increased among hard-to-reach groups such as the men having sex with men (MSM), injection drug users (IDUs), and adolescents. It has been shown that only 20–30% of sexually active young people used condoms consistently. Furthermore, these HIV-infected high risk groups have sexually transmitted hepatitis infection, especially HCV.

It has been documented that HBV infection in the general population is high (>8%) in many countries from the Southeast Asia region [1–4]. Reports showing lower infection rates of 3.2–6% from Brunei Darussalam, Indonesia, Philippines, and Thailand [5–9] are based on cases infected through vertical transmission. In tertiary care settings, HBV infection in HIV-infected population was approximately 8.7–11% [10–14]. MSMs and IDUs are at a higher risk of being infected with HBV and HIV. However, the infection rate of HBV in PLWHA is not that much different compared to the general population of which majority are infected perinatally. The most common HBV genotypes are C [15–17] and B [18, 19] followed by A. The most common genotypes found among migrants living in Thailand are C (86%) and B (11.6%) [20]. The prevalences of HBsAg among migrants from Cambodia, Laos, and Myanmar living in Thailand were 10.8%, 6.9%, and 9.7%, respectively [20]. In the last 10 years, chronic perinatal infection has decreased when the national program expanded its immunization protocol to include HBV vaccination in all children. Even though the HBV subtypes of the surface antigen [15, 18, 21] reported are adr and adw, this is not clinically significant because the HBV vaccine of either adw or ayw subtype can yield anti-a which is protective against crossinfection with other HBsAg subtypes as well [22].

Many individuals infected with HBV at birth or during early childhood and subsequently infected with HIV have asymptomatic HBV chronic infection with or without aminotransaminase elevation. Patients who develop acute hepatitis B during their adulthood will have abrupt and progressive jaundice with GI symptoms such as nausea, abdominal pain, flatulence, and bloated abdomen. The general symptoms include fatigue, dizziness, weight loss, or anorexia. The liver is usually not enlarged, and the cutaneous stigmata of chronic liver disease is not detected unless the disease has progressed to decompensated cirrhosis. Cirrhosis is more common in patients with lower levels of ALT and CD4 compared to those monoinfected with HBV [31, 32]. HIV-HBV co-infected men are much more likely to die of liver-related causes compared to monoinfected HBV patients [33]. The risk of HCC is somewhat increased in HIV-infected individuals with low CD4 counts [34]. Patients with genotype C have exhibited earlier progression of cirrhosis and HCC than those with genotype B [17].

Recently, the international HIV treatment guidelines 2011 recommend that antiretroviral therapy should be started in all HBV/HIV co-infected adolescents and adults who require treatment for chronic active hepatitis B irrespective of their CD4 cell counts. According to these new guidelines, all HIV-infected individuals with CD4 ≤ 350 cells/μL are required to start antiretroviral therapy regardless of symptoms. However, in the middle of 2011, there is evidence that this is not implemented throughout the region. Therefore, it is important to assess the treatment rates in cases with CD4 of 200–350 cell/μL to ensure treatment coverage and care among these people in order to reduce opportunistic infections in severely immunocompromised patients. Some nucleoside/nucleotide analogs for HIV treatment are effective to both HIV and HBV and therefore can be used to treat HIV/HBV co-infected patients. Furthermore, the results from the study on Tenofovir in HBV Coinfection (TICO) which was conducted in Thailand showed that a combination of tenofovir and emtricitabine or lamivudine was better than using only tenofovir [55, 56]. There was an increased loss of HBeAg when a longer follow-up period was implemented to assess HBV treatment outcome. Hepatic flares were observed in 19–25% of the patients without any severe complications. Interestingly, long-term use of tenofovir in HIV/HBV co-infected patients may prevent disease progression to end-stage liver disease in the Thai population, by slowing or reversing liver fibrosis. Currently, the Thai national guideline recommends using tenofovir with either lamivudine or emtricitabine for any HBV co-infected individuals regardless of their baseline CD4+ T-cell count. Since HBV treatment is cheap (approximately 55 USD/mo. for tenofovir plus lamivudine and 70 USD/mo. for tenofovir plus emtricitabine), this is covered by the national health scheme. However, the cost for monitoring HBV-DNA is not included in the national AIDS program, and the patients have to pay for this by themselves. Other nucleoside analogs such as adefovir, telbivudine, and entecavir are also not included because the government has decided that these drugs are not essential for the mass treatment of HBV. Moreover, it is still unclear which HBV drugs should be used for the preferred regimen in pregnant women, and infants born to HBV co-infected mothers.

After successful integration of the national expanded program on immunization (EPI) on HBV immunization, coverage of the vaccinations has increased in most countries up to 80% as seen by the results from many studies on incidence reduction of HBV and hepatocellular carcinoma in the young age group [68–72]. Due to the high prevalence of HBV infection in the region, HBV serology screening prior to vaccination in high risk groups is not necessary, for example, MSMs, IDUs, and health care workers (HCWs). Many adults, including health care workers (HCWs), cannot reimburse for HBV vaccinations. Currently, the guideline recommendation for HBV treatment and care for HCWs is not well defined. If people are aware of the complications and prognosis of chronic hepatitis, this may encourage people to have HBV serology screening and HBV vaccinations in adults older than 30 years old. For postexposure prophylaxis, hepatitis B immunoglobulin (HBIG) is required in cases that have been exposed to blood from HBV-infected individuals and are not immune to HBV according to the postexposure HBV screening test. Occupational risks can be prevented if high risk groups such as HCWs and health-related students have been immunized. This preventive policy targeting professional health care workers (i.e., hospitals and clinics) at risk of acquiring HBV infection should be integrated into the national health care system. Currently, HBV immunization is recommended to all HIV-infected patients who are susceptible and have achieved immunological success after antiretroviral therapy. However, it is important to conduct a serologic test for HBV to confirm the person’s immune status before vaccination because low CD4 levels or the use of NNRTI may affect the response to the vaccine [67]. It has been shown that in HIV-infected individuals, the immune response of generating HBs antibodies was 71.4% which was much lower compared to healthy HIV seronegative individuals. However, no adverse event has been detected.

Since HBV co-infection is more chronic, therefore the national guidelines have recommended sufficient and early screening to initiate proper treatment and care. Despite this, there are still problems for those patients who have developed resistance and have limited selection of drugs to choose from and/or intolerability. It will be a continued struggle to provide alternative treatment and other drug choices for these patients. Hepatitis B vaccination should be implemented at all levels of the population, especially high risk groups and health care workers; HBV vaccination is an urgent and necessary action that should be in place in order to reduce HBV infection. The strategic plan must cover adults older than 30 years old who may become infected and transmit the virus to others via the sexual route. Hepatitis B is preventable and immunization is better than acquiring the virus. The cost of the immunization program is incomparable to the people’s quality of life. Recently 2 new protease inhibitors, boceprevir and telaprevir, were approved by the US FDA in May 2011 and by the European Medicine Agency (EMA) in August and September 2011, respectively, for HCV treatment. The drugs can increase the efficacy and RVR when used as a triple drug therapy (with pegylated interferon and ribavirin) in HCV patients with genotype 1 [73–77], but the cost is 2-3 times higher than the standard treatment. For these new drugs, the US FDA is concerned about the adverse events such as suicidal tendencies and lack of efficacy in certain groups of people; boceprevir has been shown to cause rash and gout whereas telaprevir has been associated with TB. Both boceprevir and telaprevir can cause anemia in HCV patients. However, it should be noted that anemia is a common laboratory abnormality among patients infected with both HIV and HCV due to treatment; physicians will need to reduce the dose of their HCV medications in patients with anemia [78]. Aside from additional drug toxicities, evidence-based information from monoinfected HCV clinical trials on shorter triple drug treatment, pharmacokinetics guided optimized dose of new drugs, and potential drug-drug interactions warrant further investigations in Asian population living with HIV/AIDS. HCV Direct-Acting Antivirals (DAAs), new polymerase and protease inhibitors that are under clinical investigations with or without interferon, provide HCV patients with more treatment options. Quad therapy (2 different protease inhibitors plus pegylated interferon and ribavirin) is another option that will become available in the future regardless of the cost of the drugs. To improve tolerability and treatment coverage, the interferon-free DAA-based combination therapy may be an alternative choice for some people [79].