The 14th International Conference on AIDS
The conference organizers summarized the numbers this way:
" 14,000: The number of people who registered for the Barcelona conference.
" 14,000: The number of people who were infected with HIV
each and every day last year.
" For every person at the conference, there are over two thousand people living with HIV today.
" For every delegate, there are one thousand children who have lost one or both parents to AIDS.
" For every person at the Barcelona Conference, there are hundreds of leading health workers and biomedical and community AIDS experts around the world who could not be there to share their own
first-hand expertise.
When to Start Therapy
In general, there was more agreement than disagreement among investigators who studied the problem of when to start therapy.
The CD4 count is a key determinant in the decision making for starting therapy in treatment-naïve patients. Several investigators noted that there are small differences in progression to AIDS and death with CD4 counts between 200 and 350 and >350 cells, supporting later treatment, but before the CD4 count falls to <200. Chene, et al from the ART Cohort Collaboration said that patients have the best outcomes when treatment is started before CD4 counts fall to <200 cells. A risk calculator that demonstrates the group's methodology can be obtained from the Collaboration's website at: <www.art-cohort-collaboration.org>.
Chene G, et al. Prognosis of HIV-infected drug-naïve patients starting potent antiretroviral therapy. Abstracts of the 14th International Conference on AIDS. [Abstract TuOrB1140]
Egger M, et al. Prognosis in patients starting HAART. Lancet (July 13) 2002;360:119.
A retrospective study of more than 500 ARV-naïve patients who started treatment after 1996 found that virologic failure rates increased as CD4 counts decreased and occurred more than 10 times faster in patients with CD4 counts <200 compared to patients with CD4 counts of 200 to 349 cells. There were no differences in rates of virologic failure among patients who were started on treatment with CD4 counts between 200 and 350 and >350 cells.
Brooks, et al. Low CD4 count predicts less durable
virologic response to highly active antiretroviral
therapy (HAART) in naïve patients. Abstracts of the 14th International Conference on AIDS. [Abstract TuOrB1141]
There is also agreement that antiretroviral therapy during or close to primary HIV infection is of benefit. Fidler, et al presented a 45-patient study showing that patients treated with short-course antiretroviral therapy (SCART) showed preservation of HIV-specific CD4 T-helper cell response.
Fidler SJ, Brady MD, Oxenius A, et al. Immunological and virological effects of short course antiretroviral therapy in primary HIV infection. Abstracts of the 14th International Conference on AIDS. [Abstract TuOrB1185]
Treatment Adherence
Three studies of adherence support and outcomes from the New York State Department of Health's AIDS Institute showed that multidisciplinary adherence support at the site of medical care and prior to and during HAART therapy improves adherence to the 90% level. Treatment-naïve and -experienced patients enrolled in adherence-support activities were more likely to have undetectable viral loads, with significantly better rates of adherence among the treatment-naïve groups studied.
Waters, M et al. Differences in clinical indicators and adherence to HAART among naïve and antiretroviral treatment-experienced clients attending adherence support programs in New York State. Abstracts of the 14th International Conference on AIDS. [Abstract WePeB5812]
Novello, A. Implementing adherence programs: Lessons from the New York State adherence demonstration project. Abstracts of the 14th International Conference on AIDS. [Abstract ThPeF8185]
Structured Treatment Interruptions
The consensus among speakers who addressed structured treatment interruptions (STI) is that patient selection is still to be defined. For example, STI to restore immune system function works best in those patients whose antiretrovirals were started a short time after primary HIV infection (PHI).
Miro JM, et al, Structured treatment interruption in patients receiving HAART within 90 days of primary HIV infection: spontaneous control of viremia in only one third of cases after four cycles off therapy. Abstracts of the 14th International Conference on AIDS. [Abstract ThOrB1437]
Newer Treatments and Treatment Strategies
Plasma Viral Load Testing
Clive Loveday (UK) noted that changes in national barriers and worldwide movement of populations has resulted in redistribution of HIV subtypes, which were primarily clade B subtype in the US and Europe and clade C in Africa. The presence of multiple subtypes in a community allows HIV to genetically recombine or mutate into new forms that are "biologically more successful" than existing viruses, and this can impact on the ability to treat these new strains. Loveday stated that we are using static monitoring technologies to manage a disease that is dynamic. Therefore, viral load tests that are able to detect non-clade B subtypes are important for monitoring plasma viral load.
The test, (Amplicor version 1.5(r), Roche) which detects subtypes A-G, unlike the current version which is limited to subtype B, was approved
by the US Food and Drug Administration on July 28, 2002.
Satellite Symposium on Viral Load Testing. Abstract not available.
GlaxoSmithKline (GSK) announced in June that it has implemented a freeze in the US list price of the company's entire portfolio of anti-HIV products through January 2004. GSK will continue to provide its HIV drugs free of charge through its Patient Assistance Program for eligible low-income US residents without prescription drug benefits.
For questions regarding the Patient Assistance Program basic enrollment and continued program eligibility please call 1-.
T-20
Unlike existing anti-HIV drugs that work inside the cell and target viral enzymes involved in the replication of the virus, the fusion inhibitors
T-1249 and T-20 are designed to block fusion
of HIV with host cells before the virus enters the cell and begins its replication process. T-20 (Enfuvirtide(r), Roche), currently in Phase III clinical trials, is the most clinically advanced fusion inhibitor under investigation; US Food and Drug Administration approval is anticipated in 2003. T-20, given as 90 mg twice daily by subcutaneous injection in combination with
a background antiretroviral regimen, is well-tolerated and is optimally absorbed from the thigh, arm, or abdomen. In clinical trials, highly-motivated patients found that self-injections are easy and do not negatively impact activities of daily living.
Green J, et al. Patient survey on injection of T-20:
ease of use and impact on activities. Abstracts of the
14th International Conference on AIDS. [Abstract TuPeB4480]
Patel H, et al. T-20 is optimally absorbed from 3
different subcutaneous infection sites. Abstracts of the 14th International Conference on AIDS. [Abstract TuPeB4542]
Reasons for Genotype Testing
In a large HIV clinic in New York City, a retrospective chart review showed that the majority (85%) of patients were tested for drug selection after virologic failure. The remaining 15%, including patients about to start antiretroviral therapy, were tested for drug selection for other reasons.
Suh, JS et al. Genotype testing practices in a HIV clinic in New York City. Abstracts of the 14th International Conference on AIDS. [Abstract B10179]
Researchers from the UK discussed the value of resistance testing in ten newly diagnosed patients. Primary resistance to reverse transcriptase drugs was seen in 30%, and there was no protease resistance. Genotype-guided therapy resulted in significant declines or undetectable viral loads in all patients.
Harry T, et al. Outcome of baseline viral resistance testing in newly diagnosed HIV-infected patients. Abstracts of the 14th International Conference on AIDS. [Abstract B10177]
Wasting and HIV-Associated Adipose Redistribution Syndrome (HARS)
Kotler, et al reported on a placebo-controlled trial of 239 patients with HARS treated with human growth hormone, 4 mg/day, 4 mg every other day, or placebo. Compared to placebo, the 4 mg/day group showed significant decreases in visceral adipose tissue (abdominal fat). Both treatment groups showed significant increases in lean body mass (lean muscle) and decreases in serum cholesterol.
Kotler, D. Satellite Symposium: Long term challenges in HAART: the patient's concerns. Available at: <www.seronosymposia-educational-tv.com>.
Co-infections
HIV/HCV Co-Infection
Co-infection with hepatitis C virus (HCV)
does not adversely affect the outcomes from treatment with highly active antiretroviral therapy (HAART) for HIV according to several investigators. Physicians should therefore treat co-infected patients with HAART as aggressively as those without HCV infection
In one study of 1,199 patients 54% of the HCV- seropositive patients and 67% of the HCV- seronegative patients were prescribed HAART.
Physicians may be less likely to prescribe HAART to patients infected with both HCV and HIV for fear of liver complications. In this study, fewer patients with HCV seropositivity had received HAART, resulting in relatively high incidences of AIDS and death in this group.
In a subgroup of 429 HCV-seropositive patients with baseline CD4 cell counts between 50 and 200 cells/mm3, risk of death was increased
(relative hazard ratio, 1.51, 95% confidence interval, 1.01-2.27). However, after correction for differences in exposure to effective HAART among HCV-seropositive and HCV-seronegative patients, HCV seropositivity was not independently associated with CD4 cell decline, death, progression to AIDS, or immune reconstitution after HAART.
Combined therapy with pegylated interferon and ribavirin in co-infected patients on HAART is safe with no significant changes in CD4 counts.
Qurishi N, et al. Effect of antiretroviral therapy on liver related mortality in HIV/ HCV infected patients. Abstracts of the 14th International Conference on AIDS. [Abstract ThPeC7490]
Other studies showed good virologic response of around 45% with interferon and ribavirin. No patient had viral load increase during treatment.
Efficacy and safety of therapy with interferon and ribavirin in HIV infected patients with chronic hepatitis C. Abstracts of the 14th International Conference on AIDS. [Abstract WePeB6018]
Daily alfa interferon/ribavirin was significantly more effective at week 12 than the 3-times-weekly regimen, suggesting that higher sustained virologic responses can be achieved with
pegylated interferons. The high rate of discontinuations (23%) demonstrates the impact of significant adverse reactions and the need to develop strategies to monitor and manage side effects and support treatment adherence.
Sulkowsi M, et al. Multi-center, randomized, open label study of the safety and efficacy of interferon alfa-2b plus ribavirin for the treatment of hepatitis C in HIV-infected persons. Abstracts of the 14th International Conference on AIDS. [Abstract ThPeC7496]
In a study of HIV/HCV co-infected patients, the incidence of symptomatic hyperlactatemia (lactic acidosis) was not greater in co-infected patients on pegylated interferon/ribavirin and HAART than in published rates of lactic acidosis in patients without HCV on HAART alone (6 per 606 patient years vs 7 per 516 patient years, respectively).
Smith, DM. Symptomatic hyperlactatemia during a large hepatitis C treatment trial in HIV/HCV co-infected participants on stable antiretroviral therapy. Abstracts of the 14th International Conference on AIDS. [Abstract MoOrB1059]
Hepatitis B
Cooper, et al presented the results of a double blind, placebo-controlled 48-week trial of once-daily 300 mg tenofovir (Viread(r); Gilead) added to a stable existing HAART regimen in 12 HIV/HBV co-infected patients with HBV DNA viral loads >1,000,000 copies. Plasma HBV DNA concentration decreased by 4.44 and 1.23 log10 for tenofovir- and placebo-treated subjects, respectively (P = .05). There was no difference in the response between lamivudine (3TC; Epivir(r)) sensitive and resistant subjects. Although the numbers are small, the results support the value of tenofovir as a well-tolerated option of treatment of HIV/HBV co-infection in patients receiving HAART.
Cooper D, et al. Anti-hepatitis B virus activity of tenofovir in lamivudine experienced HIV/HBV co-infected patients. Abstracts of the 14th International Conference on AIDS. [Abstract WePeB6015]
Wealthy nations must give at least US$9 billion for AIDS, tuberculosis, and malaria treatment in 2003, according to a panel of global health policymakers at the 14th International AIDS Conference. $5.5 billion of the required sum should go to the Global Fund to Fight AIDS, Tuberculosis and Malaria-three times the sum that was pledged to the Fund during 2002. The United States should provide about $3.5 billion of the total-$2.5 billion for the Global Fund and $1 billion in bilateral aid, not including
the amounts that will be spent by the governments and people of affected countries.
For more information, visit:
<http://www.globalfundatm.org/>.