HIV/HCV Coinfection: New Data Has Implications for Treatment-as-Prevention Efforts
As survivors of the early AIDS epidemic know all too well, the coinfections and comorbidities that come alongside HIV can be more deadly than the virus itself. That's why attendees at the annual Conference on Retroviruses and Opportunistic Infections (CROI) gathered to hear data presented during an oral abstract session titled "Hepatitis C Virus/HIV-Associated Malignancies."
During this session, researchers presented their findings on people living with HIV and hepatitis C (HCV). The major takeaway? For infectious disease doctors, it's important to remember that HIV cannot be treated in isolation. And for public health officials, HIV is deeply intertwined with other epidemics that vary depending on region, country, and community.
Although the research presented during this oral abstract session spanned locales, study populations, and disease states, each presentation reflected the ongoing challenges of treating comorbid conditions among people with HIV.
Curing HCV When the First Treatment Fails
The treatment of HCV was revolutionized by direct-acting antivirals (DAAs), which offer cure rates close to 100%, regardless of a person's HIV status. But what happens for that handful of individuals who are not cured?
To address this question, David Wyles, M.D., of the Denver Health and Hospital Authority in Colorado, presented preliminary results of a retreatment study of patients who failed a DAA regimen called Mavyret (glecaprevir/pibrentasvir, or "GP" for short). Although HIV-positive patients were eligible to enroll, there were so few failures that none of the 23 patients enrolled in the retreatment study had HIV.
Wyles concluded that retreatment of HCV with GP was safe and well tolerated, and there was only one viral relapse of the 23 patients studied. GP is a good choice for retreatment because it is a "next-generation" DAA with "a particularly high barrier to resistance," noted Wyles.
Should We Be Treating Acute HCV Infection Among People With HIV?
Studies also addressed the best time to start treatment with DAAs among HIV-positive patients. Unlike current guidelines for HIV, those for HCV do not recommend treatment initiation upon diagnosis. Instead, they suggest that physicians wait until the patient has had a chance to "clear" the virus, which happens in 15%-45% of people within six months of infection.
However, researchers wondered whether patients with HIV were as likely to clear the virus as those without a coinfection. Meanwhile, very little data supports the idea that starting DAA treatment during the "acute" phase of HCV infection is safe and effective.
However, according to data presented by Anne Boerekamps, Ph.D., Erasmus Medical Center, Rotterdam, Netherlands, it's perfectly safe and equally effective to treat patients diagnosed with HCV during the acute phase of infection.
To arrive at this conclusion, Boerekamps and her colleagues enrolled 80 patients in a study, of which 63 were eventually included for analysis. Those patients, who were all HIV-positive men who have sex with men (MSM), were treated with grazoprevir/elbasvir (Zepatier) and cured at equal rates compared with those seen in a clinical trial called C-EDGE.
"Our point is," said Boerekamps, "if you treat an acute [HCV infection], you can have a treatment-as-prevention effect." Boerekamps also suggested that it might be more cost effective for payers to treat HCV patients in the acute phase of their infection rather than waiting for the virus to clear.
A study from Germany shed light on the number of HIV-positive people who are able to "clear" the virus naturally after acquiring HCV. After studying clearance rates for 464 HIV-positive patients, researchers found that only 11.9% cleared the virus spontaneously. These results were presented by Christoph Boesecke, M.D., University Hospital Bonn, Germany.
"In summary, we can say that spontaneous clearance of acute hep C in the coinfection setting is a very rare event," with almost 90% of the patients developing a chronic infection that requires treatment, said Boesecke. Among the handful of patients who cleared HCV spontaneously, a clear trend was a 2-log decline in HCV RNA at week four of infection.
"The 2-log drop might be the best helpful tool in a strong predictor of the chronic course that allows identification of [individuals] early on and maybe refer them to treatment," said Boesecke, adding, that the "European AIDS clinical guidelines have been amended to support physicians in doing so."
Using Molecular Surveillance to Understand Transmission Patterns
Finally, a molecular surveillance study reminded us that, although the epidemics might be felt in local communities, solutions must be global in scale.
"Hepatitis C knows no borders," said Luisa Salazar-Vizcaya, Ph.D., University Hospital Bern, Switzerland, who presented a phylogenetic (also known as molecular surveillance) study of the cross-border clusters of HCV across Europe.
By studying the 66 genome sequences among MSM with HCV genotype 1a from 2000 to 2016, Salazar-Vizcaya was able to determine how many new infections were "domestic" to Switzerland and how many were "international."
Ultimately, she found that about three-fourths of Swiss incidence clusters are "domestic" when you classify those strains as comprising about half of the clusters. However, if you constrain the data to say that over 80% of the cluster must comprise "Swiss" strains, then nearly half of the infections are classified as "international" in origin. Many of these international strains were from clusters in the UK and Germany, although that may be because British and Germans are over-represented in a publicly available database used in the analysis, she noted.
Overall, "this suggests that joint European scale-up schemes may boost the effect of national programs of scale up of DAAs," said Salazar-Vizcaya. In addition, phylogenetics "can teach us a lot about how treatment impacts transmission."