Metabolic Complications and Hepatitis Co-infection
News from the International AIDS Conference
by Liz Highleyman
The XVII International AIDS Conference took place August 3-8 in Mexico City. This large bi-annual meeting—which this year drew more than 22,000 participants—emphasizes the social and policy aspects of the HIV/AIDS epidemic along with recent medical findings.
CD4 cell count and cardiovascular risk
In a cardiovascular presentation, researchers with the HIV Outpatient Study (HOPS) looked at the relationship between heart disease and CD4 cell count (Abstract THPE0236). The investigators evaluated 1,697 cohort participants followed from December 2001 through June 2007. Patients were categorized into four cardiovascular risk groups based on traditional risk factors according to National Cholesterol Education Program (NCEP) guidelines, and the researchers calculated rates of new cardiovascular events including heart attacks, or myocardial infarction (MI), angina, and surgery for coronary artery disease. About one-third were low risk (0-1 risk factors), 28% were moderate risk, 19% were borderline high risk, and 21% were high risk, meaning they had a greater than 20% chance of having a heart attack within 10 years.
The incidence of cardiovascular disease ranged from 0.4 per 100 person-years in the low-risk group to 3.7 in the high-risk group. As expected, traditional risk factors were strongly linked to cardiovascular disease, but there was no apparent effect with duration of use of any HAART, all NRTIs, abacavir (Ziagen, also in Epzicom and Trizivir), “d-drugs” (ddI and d4T), non-nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs). (See the Positively Aware Annual HIV Drug Guide in January/February for classes of medications.) However, having a pre-treatment CD4 cell count below 350 was independently associated with a higher risk of cardiovascular disease after adjusting for traditional risk factors (almost double the odds with a hazard ratio of 1.83).
Reyataz and lipodystrophy
Reyataz (atazanavir) is less likely to cause blood lipid abnormalities than other protease inhibitors, and researchers have explored whether it might also lower the risk of body fat changes, or lipodystrophy. Graeme Moyle from London presented results from the REAL study (Abstract MOPDB103), in which 200 participants with suppressed viral load and abdominal fat accumulation were randomly assigned to either switch from their twice-daily Norvir (ritonavir)-boosted PI to once-daily boosted Reyataz, or else stay on their current regimen. After 48 weeks, total cholesterol, LDL “bad” cholesterol, and triglyceride levels decreased significantly in the Reyataz arm. However, changes in visceral fat, subcutaneous fat, and trunk-to-limb fat ratio were similar in both groups, leading the researchers to conclude that switching to Reyataz “resulted in no significant change in body composition.”
Very early response in HIV/HCV co-infection
Rapid virological response (RVR) four weeks after starting interferon-based therapy for chronic hepatitis C predicts sustained response in both people with HCV alone and HIV/HCV co-infected individuals. But it may be possible to predict long-term response even sooner. Natalia Laufer and colleagues from Argentina analyzed HCV viral decay during the first 24 hours of therapy in 11 co-infected patients—including eight with hard-to-treat genotype 1—treated with pegylated interferon plus weight-based ribavirin (Abstract WEPDB204). Three patients achieved RVR at week four, while eight achieved early virological response (EVR) at week 12. During the first 24 hours, HCV viral load declined by an average of 99% among patients who achieved RVR and 85% among those who achieved EVR. But among patients who did not achieve either rapid or early response, HCV levels only dropped by 51%. The researchers concluded that very early assessment of viral decline “could be of clinical relevance” in evaluating whether to continue treatment, especially for people with severe side effects or in resource-poor settings where drug availability is limited.
Relapse in HIV/HCV co-infected patients
HIV-positive people do not respond as well as HIV-negative individuals to interferon-based therapy, but post-treatment relapse has been less extensively studied. Spanish researchers tested the hypothesis that HIV/HCV co-infected patients might be more likely to experience HCV relapse after completing treatment, but might do so more slowly (Abstract THAB0202). An analysis of 119 HIV/HCV co-infected and 134 HCV mono-infected patients who achieved undetectable HCV viral load after 48 weeks of pegylated interferon plus weight-based ribavirin revealed that 30% and 26%, respectively, experienced HCV relapse, a non-significant difference.
About half of the relapsers in each group experienced HCV recurrence between the end of treatment and post-treatment week 12. Among the remainder, mono-infected patients were more likely than co-infected patients to relapse between post-treatment weeks 12 and 24, but the co-infected patients were about three times more likely to do so after 24 weeks post-treatment—that is, after they had achieved sustained virological response (SVR), which is usually considered a “cure.” Patients with HCV genotype 1 or 4 were more likely to relapse, and all but one of the very late relapsers had genotype 1. HCV recurrence was detected as late as 105 weeks post-treatment, but the researchers concluded that very late relapse was rare, and suggested that “24 weeks of follow-up is still warranted to confirm SVR.”
HIV/HCV co-infection and cardiovascular disease
Coming back to cardiovascular disease, Roger Bedimo presented data from a study assessing the influence of HCV co-infection on the risk of acute MI and cerebrovascular disease (stroke) in the pre-HAART and HAART eras (Abstract THAB0205). The investigators analyzed data from more than 20,000 HIV-positive patients in the Veterans Administration Clinical Case Registry, about one-third of whom also had hepatitis C.
In accordance with previous findings, patients with HCV were less likely to have abnormally high blood lipid levels (18% vs. 27% with high total cholesterol; 55% vs. 60% with high triglycerides) or to be taking lipid-lowering medications. And while HIV mono-infected individuals had an increased likelihood of having high cholesterol in the HAART era (1996-2004) compared with the pre-HAART years (1980-1995), there was no change in the co-infected group.
In the pre-HAART era, co-infection patients had about a 40% greater risk of both MI and stroke. After the advent of HAART, co-infected patients were about 25% more likely to experience an MI (4.19 vs. 3.36 per 1,000 person-years), but the difference did not reach statistical significance. For strokes, however, co-infected patients had a 20% higher risk (12.47 vs. 11.12 per 1,000 person-years), which in this case was a significant difference. Based on these findings, the researchers concluded that “adjustment for HCV status is indicated” when assessing cardiovascular disease risk in people with HIV.
HIV/HBV co-infection
HIV-positive people exposed to hepatitis B virus (HBV) are more likely than HIV-negative individuals to develop chronic infection, but response to hepatitis B treatment in HIV/HBV co-infected patients has not been well studied. As reported in a poster at the conference (Abstract WEPDB207), researchers retrospectively reviewed the medical records of more than 5,000 patients at St. Luke’s-Roosevelt Hospital HIV clinic. They identified 355 with hepatitis B, 283 of whom received antiretroviral drugs with dual activity against both HIV and HBV, including Epivir (lamivudine), Viread (tenofovir), Hepsera (adefovir), and Baraclude (entecavir).
Patients who received these drugs and those who did not were equally likely (about 10%) to experience HBV surface antigen (HBsAg) loss, a measure of treatment success. However, people with higher baseline CD4 cell counts, and those who gained more CD4 cells after starting HAART, were more likely to clear HBsAg. The researchers concluded that “High CD4 counts at the time of HBV infection and immune restoration through [antiretroviral therapy] are the most important predictors in successful treatment of HBV in HIV infected patients.”
Liz Highleyman (liz@black-rose.com) is a freelance medical writer based in San Francisco.
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