February 25, 2005
The 12th Conference on Retroviruses and Opportunistic Infections covered a broad range of important topics in the nearly 1,000 abstracts that were presented. This article reviews a few of the small, interesting studies that have important implications for people living with HIV.
Progress is slowly being made on bringing antiretroviral therapy to resource-limited countries. Although many developing countries are able to give HIV-infected citizens free or heavily discounted access to antiretrovirals, these treatment programs are often unable to provide regular laboratory monitoring, such as CD4+ cell counts and viral load testing, because of the prohibitive costs and specialized training required to perform these tests. Thus, there is immense interest in developing new laboratory tests that are reliable, cheap and easy-to-use.
Lesley Scott, of the University of the Witwatersrand in Johannesburg, South Africa, and colleagues presented a poster at this conference (Abstract 742) on the PointCare CD4+ cell test. The test is a simple alternative to standard CD4+ cell tests: It provides a CD4+ cell count, as well as a CD4+ cell percentage and total white blood cell count, in about 20 minutes. It requires no specific training for its use. It has the advantage of providing immediate results to guide patient management and a much lower cost than standard CD4+ cell tests.
An initial study of the PointCare test by Scott et al revealed similar results to flow cytometry (the standard method for measuring CD4+ cell count) in the range where it really matters from a clinical standpoint, 200 to 400 cells/mm3. Further study needs to be conducted in clinics where the PointCare test would primarily be used. If it continues to give rapid, reliable results in those settings, it could become an important option for resource-limited clinics.
Enfuvirtide (T-20, Fuzeon) is the only fusion inhibitor approved by the U.S. Food and Drug Administration. The major side effect of this drug is injection site reactions (ISRs) -- painful, red bumps that develop at sites where enfuvirtide is injected under the skin. ISRs are nearly universal in patients who have been taking enfuvirtide for a long period of time.
Many patients who use enfuvirtide are also experiencing a loss of subcutaneous fat (lipoatrophy) in areas where they inject. A study (Abstract 838) by David Cooper, from the University of New South Wales in Sydney, Australia, and colleagues asked whether this loss of subcutaneous fat was related to the severity of ISRs. They examined 59 patients who were starting enfuvirtide while participating in the ALLIANCE study. The ALLIANCE study is a 48-week study that is attempting to determine the safety and efficacy of switching patients who have experienced nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) toxicities to an NRTI-free regimen containing enfuvirtide. Patient limb fat was assessed via dual energy X-ray absorptiometry (DEXA) scan at baseline and then at 24 weeks and 48 weeks.
Cooper et al found that 98% of the patients experienced at least one ISR, but that ISRs were generally mild and resolved within 3 days. The overall occurrence of ISRs did not vary by the amount of subcutaneous fat under a patient's skin. However, patients with the least amount of subcutaneous fat were most likely to have moderate to severe (grade 3 or 4) ISRs, as shown in the table below.
Fat Mass (kg)
|Assessments in Which|
Grade 2-4 ISRs Were
|Assessments in Which|
Grade 3-4 ISRs Were
|2.70 - 4.29||69%||22%|
|>/= 4.30||62% (P = .019)||16% (P = .017)|
The authors attribute this increased severity to patients being less able to inject the enfuvirtide into subcutaneous fat where it belongs. However, no patients in this study actually discontinued enfuvirtide because of these reactions. ISRs continue to be the major side effect of enfuvirtide. Although there are no strategies that have been proven to reduce the occurrence or severity of ISRs, patients experiencing ISRs can often find relief by experimenting with a variety of strategies until they find one that works for them. Some helpful strategies that could work are using ice packs or heating pads on the injection site or slowing down the rate of injection.
Erectile dysfunction is common among HIV-infected men, however, it often is undiagnosed unless the healthcare provider specifically asks a patient about possible symptoms. Obviously this is a conversation that many patients feel uncomfortable about initiating. A study (Abstract 875) by Nancy Crum and colleagues from the Naval Medical Center in San Diego, Calif., found that 17 (26%) of 65 HIV-infected men reported symptoms of erectile dysfunction, but only 3 (18%) of the 17 were actually taking prescription medicine for this problem.
When attempting to determine the predictors for erectile dysfunction, Crum et al found that the strongest predictor of erectile dysfunction was increasing age, which is not a surprise. Longer duration of HIV infection, use of protease inhibitors and lipodystrophy were also associated with erectile dysfunction. On the flip side, only 12% of the men with erectile dysfunction had low testosterone levels while 26% had clinical depression. Most men with erectile dysfunction had not been diagnosed with the disorder prior to their enrollment in this study.
This study confirms what is seen in clinical practice: Erectile dysfunction is common among HIV-infected men, especially older men, and often goes undiagnosed. Although low testosterone levels did not account for a majority of the erectile dysfunction cases, it represents a treatable cause of erectile dysfunction and should be ruled out. The authors are planning future studies on the causes of erectile dysfunction and the response to therapy. Practitioners should make sure to ask about sexual function -- including hitting upon safer sex messages. Treatment should be given as necessary for erectile dysfunction since this is clearly a vital part of a patient's well being.
Highly active antiretroviral therapy (HAART) has led to a decrease in certain HIV-associated cancers, such as Kaposi's sarcoma and primary brain lymphoma.1 In addition, HAART has been shown to improve HIV-infected patients' response to Kaposi's sarcoma therapy.2 It is not known what effect HAART has on treatment for primary brain lymphoma, however.
Italian researcher Andrea Antinori and colleagues reviewed 118 cases of primary brain lymphoma, which were admitted to 11 HIV referral clinic centers throughout Italy from 1992 to 2004 (Abstract 907). Most patients had an extremely low CD4+ cell count at the time of primary brain lymphoma diagnosis (81%). Overall, their outcomes were poor. Patients who never received HAART, or who had received HAART prior to their primary brain lymphoma diagnosis, lived for an average of 60 days after diagnosis. Patients who began HAART after their primary brain lymphoma diagnosis lived an average of 90 days after diagnosis. No significant difference in patient survival time was noted in the pre- versus post-HAART era. On multivariate analysis, the risk of death was reduced in patients who received radiation or chemotherapy (hazard ratio = 0.37) and those who started HAART for the first time after their primary brain lymphoma diagnosis (hazard ratio = 0.41).
This study highlights the importance of diagnosing HIV-infected patients earlier in the course of HIV infection, when they have higher CD4+ cell counts. That way, antiretroviral therapy can be initiated promptly when necessary, and this devastating AIDS-defining illness can be avoided altogether.
A prior report suggested that HIV-infected individuals are 4 times more likely to develop lung cancer3 as compared to HIV-uninfected individuals. This increased risk is much smaller than that seen for Kaposi's sarcoma (relative risk = 2000) or non-Hodgkin's lymphoma. It is unclear how much of this elevated risk is due to damage to the immune system or because HIV-infected people smoke cigarettes more than HIV-uninfected people do.
Eric A. Engels, from the Johns Hopkins University School of Medicine, and colleagues examined the incidence of lung cancer in 5,242 HIV-infected patients at Johns Hopkins Hospital in Baltimore, Md., from 1989 to 2003, and compared it to a national cancer registry and a cancer registry from the Detroit, Mich., metropolitan area (Abstract 908). The risk of lung cancer among the Johns Hopkins patients was found to be 8 times higher than that of the national average and 5 times higher than that in Detroit. The incidence of lung cancer increased over time, and was strongly related to age. There did not appear to be any evidence that immune damage was related to lung cancer among people with HIV, although the sample size was relatively small: Only 37 HIV-infected patients at Johns Hopkins developed lung cancer.
This study supports what healthcare practitioners already know: It is important for patients living with HIV to quit smoking to help avoid lung cancer. This study cannot definitively rule out a role for immune damage as a contributing factor to the development of lung cancer, but it does suggest that immune damage is not as strong a factor as smoking. Unfortunately, it looks like non-AIDS defining malignancies may become more common as people infected with HIV live longer with continued improvements in clinical care.