Coverage of 2007 CROI (Conference on Retroviruses and Opportunistic Infections)

February 25–28, 2007, Los Angeles, CA

Notes from CROI: Summaries of presentations

February 27, 2007

An interesting and wide-ranging session titled “Metabolic and Cardiovascular Complications of HAART” filled a large meeting room Monday morning at the 14th Conference on Retroviruses and Opportunistic Infections. Metabolic complications refer to the impact of anti-HIV therapies on the body’s ability to process fats, sugars and proteins. Included in these complications are body composition changes (lipodystrophy), diabetes and cholesterol changes. Cardiovascular complications include the impact of anti-HIV drugs on the function of the heart and heart disease more generally. Nine presentations spanned topics such as the rate of liver and heart disease in two large studies, called FIRST and SMART, to the effectiveness of Zetia for treating high cholesterol. Below are summaries of each presentation.

The FIRST Study: CD4+ cell counts and non-opportunistic disease
Jason Baker of the University of Minnesota presented data from the FIRST study, examining the relationship between CD4+ cell counts and the risk of non-opportunistic diseases in people taking anti-HIV drugs. The FIRST study examined three different anti-HIV drug strategies for people starting therapy for the first time.

Not surprisingly, the researchers found a strong relationship between low (below 200) CD4+ cell counts and the risk of opportunistic diseases. When looking at people with CD4+ cell counts above 200, non-AIDS-defining conditions or “non-opportunistic” diseases (such as liver, heart, kidney diseases and a number of different cancers) were a greater risk. The risk for these conditions was lower for people with higher CD4+ cell counts.

ACTG 5142: Heart disease
This presentation looked at the rates of heart disease in ACTG study 5142, which compared three class-sparing drug regimens. In this study, people took Kaletra (lopinavir/ritonavir) plus 2 NRTIs (NNRTI-sparing); Sustiva (efavirenz) plus 2 NRTIs (PI-sparing); or Kaletra plus Sustiva (NRTI-sparing).

Researchers found that people taking only NRTIs had more increases in blood fats (lipids) than people taking either Kaletra or Sustiva. This may surprise some, as both Sustiva and even more so Kaletra have long been associated with increased lipids. Also somewhat unexpectedly they found higher rates of facial wasting in people taking NRTIs along with Kaletra than those taking NRTIs alone, or with Sustiva. This was true for any NRTI—with the highest rates, not surprisingly seen in people taking Zerit (stavudine, d4T).

Small cholesterol study
This presentation looked at the drug Zetia (ezetimibe) to treat high cholesterol in people taking HIV drugs. Zetia works differently than many other cholesterol-lowering drugs that are widely used by people with HIV, like the statin drugs. David Wohl reported results from a small study where two groups were given six-week courses of Zetia, compared to a placebo. A small but significant reduction in LDL, or bad cholesterol, was noted. No effects on triglycerides or HDL (good cholesterol) were seen. The reduction was smaller than typically seen with statin inhibitors, but this might be due to the short length of treatment.

New Fill/Sculptra
A study compared two groups of people using Poly-L-Lactic acid (New Fill/Sculptra) to treat facial wasting—the loss of fat on the face due to HIV infection or anti-HIV drugs. One group received injections of this substance at the beginning of the study while the other group waited 24 weeks to begin therapy. Both were given four injections, spaced two weeks apart.

The researchers reported no significant gain in skin thickness in either group, as measured by DEXA scan. There was no significant difference seen between people who started Sculptra right away and those who delayed treatment. One audience member proposed that this was due to the substance being given under the skin (subcutaneous) rather than within the skin, called intradermal. Sculptra is approved for the treatment of HIV associated facial wasting.

SMART Study: Comparing two strategies
The SMART study was designed to compare two anti-HIV drug strategies: continuous therapy vs. CD4+ cell count guided intermittent therapy. As widely reported, the study was stopped early when it was found that people in the intermittent therapy arm had higher rates or sickness and death. The presenters confirmed earlier reports that there were slightly higher rates of cardiovascular (heart) disease in the intermittent therapy group, although they were unable to see an immediate increase in risk when people stopped taking anti-HIV drugs.

Bone loss study
Another presentation examined the use of Fosamax (aldenorate) to treat bone loss in people with HIV. Bone loss is becoming a greater concern for people with HIV due to the aging population of people living with HIV and the long-term use of anti-HIV drugs which may contribute to bone loss.

This study examined 82 people, half taking Fosamax one a week, plus calcium and vitamin D while the other half took a placebo along with calcium and vitamin D. Compared to calcium and Vitamin D alone, the researchers reported that people taking Fosamax gained more bone mass in three of the four areas measured. Of note, people of African ancestry gained somewhat less bone mass in one of the measured areas.

Growing negative research of Zerit
Dr. Fleishman of Massachusett General Hospital looked at insulin sensitivity in HIV-negative people taking Zerit (stavudine, d4T) for four weeks. The researchers reported small, but significant changes in the ability of cells to absorb glucose after only four weeks of therapy with Zerit. These changes were strongly associated with changes in the function of mitochondria—small structures inside cells that generate energy. (For more information, read Project Inform’s publication, Mitochondrial Toxicity.) Zerit has largely been abandoned in the US, but it is widely used in the developing world. This study adds to a growing body of negative research on Zerit and further calls into question its widespread use in the developing word.

Kaletra and fat loss
A study examined whether Kaletra alone, after a period of standard three-drug therapy, would result in less loss of fat (lipoatrophy) than continuing on a traditional three-drug regimen of Kaletra plus Combivir. In this study, everyone started taking Kaletra plus Combivir (AZT plus 3TC). After using the three-drug combination for 24 to 48 weeks, one group stopped taking the Combivir but continued taking Kaletra alone. The other group remained on the three-drug regimen.

After 96 weeks researchers assessed changes in fat, both in the limbs and around the gut in the two groups. They found that people taking continual traditional three-drug therapy tended to gain fat in their midsection while losing fat in their arms and legs while people who stopped the Combivir and continued on Kaletra monotherapy tended to gain fat in both areas.

New growth hormone product
The final presentation looked at using a growth hormone product to treat the gain of fat associated with HIV treatment. The study didn’t look at growth hormone itself, but a substance called TH9505 thought to raise the natural production of growth hormone. J Falutz of Montreal’s McGill University found a significant reduction in abdominal fat along with small improvements in lipids among people receiving TH9505 compared to placebo. Since this was the first presentation of this data, the significance of this finding can’t yet be fully determined.

As people live longer with HIV, the complications of long-term anti-HIV therapy become increasingly important. Of particular interest for many are the metabolic and cardiovascular affects of HIV drugs. This was made clear by both the studies presented and the overflow crowd present to listen.