Managing HIV/HCV Co-infection – Still Much to Learn

Managing HIV/HCV Co-infection – Still Much to Learn

D r T a d d S L a z a r u s

Attending Physician, St Vincent’s Hospital (NY) and Director of Medical and Scientific Affairs,

Roche Diagnostics

(excerpted)

More than one-third of HIV patients in the US and Europe are co-infected with the hepatitis C virus (HCV). Although both diseases can be successfully managed in mono-infected patients, co-infection remains extremely problematic for many reasons, in large part due to a lack of research.  Because risk factors for both infections are similar, HCV infection is often diagnosed during or shortly after HIV diagnosis. Following an accurate diagnosis of co-infection, aggressive treatment and monitoring for both diseases is indicated, yet much remains unknown about the most effective timing, duration and potential interaction of current therapies.  The improvement of patient outcomes will continue to depend on additional research surrounding the co-evolution of diagnostic tools and therapeutic agents.

HIV/HCV co-infection rates in the US and Europe (are) as high as 35% – and an alarming 80% for intravenous (IV) drug users.  In the meantime, clinicians continue to collate and act upon what is currently known about the pathological synergy of these two diseases, with emphasis on accurate, timely diagnosis.  A lack of conclusive guidelines on the best treatment and management requires urgent attention from the scientific and clinical communities.

Does HCV co-infection expedite the development of AIDS?   Mounting evidence suggests such a trend, but  this is still subject to on-going debate.  On the other hand, researchers have concluded that HIV expedites the progression of HCV-related liver disease. co-infected patients have a three to seven times greater risk of developing cirrhosis and liver failure, and are three times more likely to die of a hepatitis-related illness than an AIDS-related illness.

Research presented in February 2004 at the 11th annual Conference on Retroviruses and Opportunistic Infections, cited end-stage liver disease (ESLD), not AIDS, as the leading cause of death in HIV/HCV co-infected patients. morbidity and mortality of AIDS may have masked the long-term effects of opportunistic infections such as HCV.  A recent increase in liver disease among co-infected patients may be evident with the (rise) of more potent HIV therapies. In the past, it is clear that co-infection compounds the challenges in treating AIDS and chronic HCV.  Consequently, there is a growing dependence on diagnostic tests to direct and monitor therapy.  Liver biopsies can be useful in assessing the level of fibrosis in HCV-infected individuals. Biopsies are extremely invasive, however, and may not be required for a physician to make the decision to treat a patient. This makes other non-invasive measures important in the treatment decision.
some researchers have concluded that patients with low CD4+ cell counts should delay HCV treatment until HAART has improved the patient’s immune status. Others speculate that earlier initiation of HAART – even before reaching 200–350 CD4+ cells – might actually decrease the incidence and progression of end-stage liver disease in (the) co-infected.  The next few years will certainly see valuable advances in treatment and management  for co-infected patients. Until then, clinicians have a variety of reliable diagnostic tools available that can help them achieve the timely identification of co-infected patients, tailor(ing) therapy to each patient with the goal of ensuring that both diseases are effectively managed.

scientific and clinical communities.

(excerpted)

a report by

byline: Larry: MSM transmission and case definition of HCV in AID...

byline: Larry: MSM transmission and case definition of HCV in AID...: " The European AIDS Treatment Network (NEAT) Acute Hepatitis CInfection Consensus PanelJu¨rgen K. Rockstroh (excerpts) (1) Case definiti..."

MSM transmission and case definition of HCV in AIDS infection.

 

The European AIDS Treatment Network (NEAT) Acute Hepatitis C

Infection Consensus Panel

Ju¨rgen K. Rockstroh

(excerpts)

(1) Case definition and diagnoses

(2) HCV transmission in MSM

(1) Case definition and diagnosis of acute HCV

infection in HIV-infected patients

Case definition and diagnosis of acute HCV infection in HIV-infected patientsAcute hepatitis C virus (HCV) infection is defined as the first six months after exposure to HCV. This definition is arbitrary as there is a lack of evidence on when ‘acute’ infection becomes ‘chronic’ and determining the precise timing of infection is usually problematic. As the majority of individuals with acute HCV infection are asymptomatic clinical diagnosis has a low sensitivity.  Differentiating between acute HCV infection and an exacerbation of chronic HCV infection clinically, virologically and immunologically is difficult in the absence of recent negative HCV RNA and antibody results. A serological test does not exist to differentiate between acute and chronic infection.  One third to a half of individuals with acute HCV infection experience symptoms attributable to an acute illness, although symptoms are non-specific.  The first marker of HCV infection is serum or plasma HCV RNA detected via nucleic acid test (NAT) as early as one week post infection. HCV antibody responses may be delayed or absent in HIV-infected individuals with two thirds positive at three months and 5% remaining negative up to one year after infection.  Fluctuations in HCV-RNA levels during the acute phase of HCV infection are characteristic in HIV-uninfected  individuals and may be of value in suggesting a diagnosis of acute hepatitis C.

  

(2) HCV transmission in MSM

Studies in MSM have shown HIV infection and intravenous drug use to be independently associated with the presence of HCVantibodies. In early reports, evidence for sexual transmission was weak with conflicting evidence of an association with sexual risk behaviour.  Recent studies investigating factors underlying HCV transmission in HIV-infected MSM have provided further evidence for an association with certain sexual practices including fisting, using sex toys, and group sex.  Non-injecting drug use is also associated, probably because of the influence on sexual behaviour but transmission through sharing contaminated devices may also contribute. There is an association with bacterial sexually transmitted infections notably syphilis and lymphogranuloma venereum. The mechanism of sexual transmission remains uncertain but the association with traumatic sexual practices and ulcerative STIs affecting the mucosa of the rectum provides some clues. HCV RNA has been detected in semen and more often in the HIV-infected, although one study failed to detect HCV RNA in the semen of most HIV-infected men even during acute HCV infection. Group sex may facilitate transfer of infected material. Other causes of disruption of the ano-rectal mucosa, including surgery, may contribute to the risk. There is no evidence that HIV-infected men are more susceptible to HCV infection due to immunological deficits, or that a more virulent HCV strain is being selected.  Phylogenetic analyses of transmitted HCV strains show clustering consistent with transmission among a social and sexual network of HIV-infected MSM, which extends nationally and internationally. Although the majority of patients present with two or more risk factors described above, cases of acute HCV infection are seen in MSM who report only unprotected anal intercourse. Although current outbreaks have been largely confined to HIVinfected MSM, cases have also been reported in HIV-uninfected individuals.5 ULN in less than 2 % [9], minimizing the possibility of classifying ‘‘chronic’’ HCV infection as ‘‘acute’’. The first marker of HCV infection is serum or plasma HCV RNA detected via nucleic acid test (NAT) as early as one week post infection.  HCV antibody responses may be delayed or absent in HIV-infected individuals with two thirds positive at three months and 5% remaining negative up to one year after infection. Fluctuations in HCV-RNA levels during the acute phase of HCV infection are characteristic in HIV-uninfected individuals and may be of value in suggesting a diagnosis of acute hepatitis C 

Acute hepatitis C in HIV-infected individuals –

recommendations from the NEAT

consensus conference