Skip Navigation LinksHome > May 2010 - Volume 18 - Issue 3 > Selected Reports From 2010 CROI (17th Conference on Retrovir...
Infectious Diseases in Clinical Practice:
doi: 10.1097/IPC.0b013e3181de0bf6
IDCP Snapshots

Selected Reports From 2010 CROI (17th Conference on Retroviruses and Opportunistic Infections), San Francisco, February 16-19, 2010

Bonilla, Hector MD

Free Access
Article Outline
Collapse Box

Author Information

From the Northeastern Ohio Universities College of Medicine, Rootstown; and Summa Health System, Akron, OH.

Reprints: Hector Bonilla, MD, 75 Arch St, Suite 506-Akron, OH 44304. E-mail: Bonillah@summa-health.org.

Dr Bonilla discloses that he is the principal investigator in a trial sponsored by Cubist and BioCryst pharmaceuticals.

Back to Top | Article Outline

VIROLOGY

Four main groups of the human immunodeficiency virus (HIV) associated with HIV disease are M, N, O, and P. Groups M and N originate from chimpanzee (SVcpzptt), and for groups O and P, their origin is still unknown.

In a study of a population of gorillas in Cameroon by collecting stool samples, a SIVgor (simian virus) was detected and was present between 4% and 14% in the collected samples. This virus was phylogenetically related to groups O and P. It is unknown if this virus (SIVorg) is capable of causing any disease in this gorilla population, and its reservoir is unknown.1

In 2004, a 62-year-old Cameroonian patient living in Paris, France, was found to be infected with HIV-1 group P. Abbott Diagnostics conducted a study in Cameroon, a country endemic to HIV groups M, N, and O, to search for the existence of more cases of HIV-1 group P. Using reverse transcription-polymerase chain reaction, those investigators found a second case of HIV group P-infected patient. He was a 54-year-old man from Jamot Hospital in Yaonde, Cameroon. This virus shares a common ancestor with SIVgor. This finding shows the emergence of new HIV human variant.2

Since the introduction of highly active antiretroviral therapy (HAART) in 1996, a dramatic decline in HIV mortality has been noticed with the effect on the risk of developing cancer. The acquired immunodeficiency syndrome-related cancer (AIDS-CR) (Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and the non-AIDS-CR have been increased in the HIV population. From the National Cancer Institute, cancer registry records of 372,364 AIDS diagnosis between 1980 and 2006 were reviewed; 79% males, mean age of 36 years, 37% whites, 42% non-Hispanic blacks, 42% MSM, and 27% IVDU. Cancer risk was measured by the standardized ratio (AIDS-CR/cancer in general population) and found that the number of AIDS-related cancer was significantly higher in the HIV-positive group than that in the non-HIV-positive population. In addition, the non-AIDS-CR showed a significant increase in the number of anal carcinoma (27-fold), liver cancer (3.7-fold), lung cancer (3-fold), and Hodgkin lymphoma (9.1-fold). In contrast, a decline in accumulation incidence of malignancies was associated with HAART, which is possibly related with better immune status. In the HIV-infected individual, the cancer burden is associated with a longer survival and age; therefore, it is important to implement cancer prevention and treatment.3

In another study by Kaiser Permanente on a cohort of 19,280 HIV-positive, 90% males, 75% MSM, 44% whites, and 39% smokers, the most significant non-AIDS-CRs were anal carcinoma, Hodgkin lymphoma, and oral cavity/pharynx cancers. Again, the presence of malignancies was associated with lower CD4 cell count and no association with HIV viral load.4

Back to Top | Article Outline

ADVANCES IN ANTIRETROVIRAL THERAPIES

LEDGINs are a novel class of second-generation antiretroviral of integrase inhibitor. LEDGF/p75 was identified in 2003 as a cellular cofactor in the integration process.5 From exploring more than 200,000 compounds, it was found that 25 chemical compounds were capable of binding this factor. By chemistry optimization, a new compound, CX04328, binds to this integration process like raltegravir and elvitegravir, and no cross-resistance was found. A new compound, CX06387, has shown a greater potency.

The HIV capsid assembly and maturation is essential for viral infectivity. By developing an in vitro capsid-like structure, 2 chemotypes of CAP inhibitors were developed (benzodiazepines and benzimidazoles). Those chemotypes have no cross-resistance with NNRTI, NRTI, PIs, or integrase inhibitors. Those compounds reduce viral production by making a defective virus that lack a cone structure characteristic of the mature virus.6

TBR-652 is a CCR5 and CCR2 inhibitor. The CCR2 is present on the surface of the monocytes, dendritic cells, and memory T cells and is associated with inflammatory diseases such as arthrosclerosis and metabolic syndrome. The potency, safety, and tolerability of PK and CCR2 activity were evaluated in a randomized, double-blind, placebo-controlled dose-escalating study. One log reduction was achieved at doses greater than 25 mg (range, 25-150 mg) after 10 days of use. It has a long half-life (23-48 hours) with mild grade 1 adverse effects.7

Back to Top | Article Outline

HIV, INFLAMMATION, AND CARDIOVASCULAR DISEASE

The incidence of cardiovascular disease (CVD), myocardial infarction (MI), and coronary arterial disease (CAD) in smokers is high in developed countries and is associated with an increase in the risk of CVD. In the HIV population, smoking has been shown to increase morbidity and mortality. In the HIV-negative population, smoking cessation has resulted in a significant decrease in CVD 1 to 2 years after stopping smoking, and 5 years after stopping, risk of CVD is the same as that in never smokers.

A study from DAD that included 33,308 HIV-positive patients from Europe, United States, and Australia looked at the benefit of stopping smoking measured by the incidences of MI, CAD, endarterectomies, stroke, and death from CVD. In this study, most were males and a significant amount was drug users and whites. Approximately 400 MI cases have been recorded. Increased risk rate was observed for MI, CAD, and CVD in smokers, with a significant decrease in the risk reduction after smoking cessation; however, there was no effect in the reduction of mortality (Table 1).8

Table 1
Table 1
Image Tools

The HIV-positive individuals have a higher risk of acute coronary syndrome that occurs more than a decade younger than control with a higher chance of restenosis. A study from the Kaiser Permanente group in California has shown that HIV-positive patients have higher rates of hospitalization for acute coronary syndrome and angioplasty. In addition, an HIV-positive male has more chance to develop subclinical atherosclerosis.

From the SMART study, we learned that HAART significantly reduced the risk for CVD, with excess events in the drug conservation arm. In the same study, inflammatory markers, such as interleukin 6, D-dimer, and CRP, were associated with all-cause mortality.

Two major techniques have been used to evaluate the risk for CVD: (1) flow-mediated dilation (FMD) and (2) high-resolution ultrasound of the internal carotid artery (cIMT). The initiation of HAART is associated with an improvement in FMD; an effect noticed as early of 4 weeks on therapy and persists for up to 24 weeks without reaching a complete restoration of vascular health. The cIMT showed more carotid plaques in HIV-positive individuals associated with CVD. These changes in FMD and cIMT are associated with a higher level of inflammatory markers including interleukin 6, CRP, D-dimers, lipopolysacaride, and fibrinogen.

In the era of HAART, even with the long-term suppression of HIV infection, a decrease but not normalization in T-cell activation, inflammation, and distensibility of the arterioles and markers of aging has been noted. Also, the CMV-specific T-cell response was found to be higher in the HIV-treated patient with T-cell activation, suggesting its possible role in subclinical atherosclerosis.9-12

In addition, in a couple of studies (SUN/Athena), a low CD4 cell count, older age, and BMI greater than 25 kg/m2 were associated with the progression of CVD measured by cIMT, and a low HIV viral load (<400 copies) was associated with less CVD progression.13,14

Back to Top | Article Outline

REFERENCES

1. Etiene L, et al. Molecular epidemiology of SIV infection in wild-living gorillas in western equatorial Africa. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 9-Oral presentation 24.

2. Vallari A, et al. HIV-1 group P: confirmation of group P in Cameroon. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 9-Oral presentation 25.

3. Simard E, et al. Cancer incidence and cancer-attributable mortality among person with AIDS in the US. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 9-Oral presentation 27.

4. Silverberg M, et al. Immunodeficiency, HIV RNA levels and risk of Mon-AIDS-defining cancer. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 9-Oral presentation 28.

5. Christ F, et al. First in class inhibitors of LEDGF/p75 integrase integration and HIV replication. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 12-Oral presentation 49.

6. Titolo S, et al. Discovery of potent HIV-1 capsid assembly inhibitors. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 12-Oral presentation 50.

7. Palleja S, et al. Safety and efficacy of TBR 652, a CCR5 antagonist, in HIV-1 infected ART-experienced, CCR5 antagonist-naive patients. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 12-Oral presentation 53.

8. Petoumenos K, et al. Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D.A.D. study. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 37-Oral presentation 123.

9. Hsue P, et al. HIV, inflammation and cardiovascular disease. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 20-Oral presentation 70.

10. Hsue P, et al. Rapid progression of atherosclerosis at the carotid bifurcation is linked to inflammation in HIV-infected patients. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 37-Oral presentation 125.

11. Ho J, Hsue P, et al. Earlier initiation of ART in HIV-infected individuals is associated with reduced arterial stiffness. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 137-Poster Presentation 707.

12. Hsue P, et al. Inflammation is associated with endothelial dysfunction among individuals with treated and suppressed HIV infection. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 137-Poster Presentation 708.

13. Baker J, et al. Progression of carotid intima-media thickness in a contemporary HIV cohort. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 37-Oral presentation 126.

14. van Lelyveld S, et al. Incomplete immune recovery on HAART is associated with significant more cardiovascular event and trend towards more non-AIDS related malignancies in Dutch ATHENA cohort. Paper presented at: 17th Conference on Retroviruses and Opportunistic Infections); February 16-19, 2010; San Francisco, CA. Session 138-Poster presentation 714.

© 2010 Lippincott Williams & Wilkins, Inc.