• Off to Durban
• Viral Load
• Drug News
• Wrapping Up

The XIIIth International AIDS conference was held this July on the continent hardest hit by HIV and AIDS. The host city, Durban, is located on the east coast of South Africa, a country where life expectancy is expected to drop to age 36 by the year 2010. The high rates of HIV infection and AIDS-related deaths are not the only problems facing the citizens of South Africa. The country is led by President Thabo Mbeki, who has been under fire recently for giving credence to the theory that HIV does not cause AIDS. In addition, only 15% of the country's wealthiest citizens have health insurance that allows them access to the medications used to treat HIV. Against this backdrop, HIV researchers and activists from around the world came together for a meeting with both political and scientific significance.

Off to Durban

Michael Marco described his initial apprehension about traveling to South Africa. He knew the extent of the AIDS crisis in that country and feared that the experience would be depressing. When he arrived, he found his fears to be largely unfounded. While their situation is far from ideal, the people of Durban were kind, generous, and welcoming.

At a time when HAART has significantly decreased the morbidity and mortality associated with HIV/AIDS in the United States, its cost keeps it out of reach for most people in the developing world. Government inaction in the face of HIV has led many South Africans to advocate for their own care. Mr. Marco spoke highly of Treatment Action Campaign, a grassroots advocacy organization that is working with Doctors Without Borders to increase access to HIV medications. American pharmaceutical companies have offered to sell HIV drugs at reduced prices in Africa, but even with the reductions, the cost of AZT/3TC therapy would still be $2000 per person per year. In Thailand, where generic medications are produced, the cost is $200 per person per year. Drug companies were put to shame for refusing to allow the production of generic antiretrovirals in Africa and sacrificing human lives for a profit margin.

Activism and advocacy shared center stage at the conference with scientific information. Jules Levin reported on a variety of scientific topics from the conference, some of which are described below. For more information, please visit his organization's website at www.natap.org.

Viral Load

To Blip or not to Blip

Viral load is used in the developed world as a way to track HIV progression. Of interest to many doctors and the HIV-infected patients they treat is the significance of "blips" in viral load. A blip is an increase in viral load after an undetectable level has been reached. The increase is followed by a return to an undetectable level. A study from England showed that people who experienced a blip did not have as high an increase in CD4 count as those who never had a blip. Intuitively, this makes sense - if there are more copies of HIV in the blood, more immune system cells are destroyed.

This was the first study to show exactly how damaging a blip can be. The study examined patients initiating HAART therapy whose viral load went undetectable (less than 400 copies) within six months. The patients were divided into two groups - those who experienced a blip and those who did not. About 850 people enrolled in the study, and more than 130 have already been followed for over a year. Of those patients, 56% stayed undetectable and 44% had a blip. A year and a half after starting HAART, the patients who had a blip had an average CD4 count increase of 155 cells, while those with no blip had an average increase of 269 cells, a statistically significant difference. The researchers concluded that treatment intensification should be considered in patients who blip. More importantly, the most effective way to avoid blips altogether is to take antiretrovirals as they are prescribed.

How low can you go?

Another lingering question about viral load is whether it is clinically beneficial to have a viral load less than 50 copies (i.e., undetectable by the Roche Ultrasensitive test), or whether a viral load of less than 400 copies (i.e., undetectable by a standard test) delays disease progression to the same extent. In a recent study from New York, two groups of patients were identified. Members of the first group (54 patients) were undetectable by both tests, while members of the second group (41 patients) were undetectable by the standard test but not the ultrasensitive test. After two years, the clinical characteristics of the two groups were similar - there were similar rates of opportunistic infections and no AIDS-related deaths. There were similar increases in CD4 cell counts and no significant difference in the number of people from each group whose viral load increased to above 400 copies. Differences may appear further down the line, but for now it seems that less than 400 copies may be low enough to delay disease progression.

Men, Women and Viral Load

A group of researchers from Baltimore followed 3,380 IV drug users for almost 10 years, and unearthed some interesting differences between the men and the women that they followed. The researchers analyzed viral load information from 202 men and women who were infected with HIV over the course of the study. The average initial viral load measurement was much lower in women than in men (15,103 vs. 50,766 copies). Overall, 19% of the men (29/156) and 33% of the women (15/46) progressed to AIDS, and the time to progression was about four years in both men and women. Among the men, average initial viral load was 77,822 copies among those who progressed to AIDS compared to 40,634 copies among those who did not, a significant difference. Among the women, average initial viral load was 17,149 copies among those who progressed to AIDS compared to 12,043 copies among those who did not, which is not a significant difference. This indicates that initial viral load may predict disease progression in men but not in women.

The Department of Health and Human Services currently recommends that a treatment-naïve patient with less than 500 CD4 cells or a viral load greater than 20,000 copies be offered antiretroviral therapy. Considering the data from the Baltimore study, the recommendation of 20,000 copies may be too low, especially for men. It may be most useful to consider CD4 cell count when deciding whether to initiate therapy.

Drug News

An Option for Salvage Therapy

A promising option for patients with HIV resistant to multiple protease inhibitors (PIs) was presented. A study by a Belgian researcher followed 57 patients who received a new protease inhibitor called ABT-378/ritonavir (also known as lopinavir) in place of their current PI. To qualify for this study, patients had to be naïve to NNRTIs (drugs like Sustiva and Viramune) and have multiple PI experience (a history of treatment with at least 2 protease inhibitors for at least 3 months each). In the study, ABT-378/r was given twice a day in combination with Sustiva once a day and NRTIs (drugs like AZT and 3TC) chosen by a doctor. 28 patients received the standard dose of 400 mg ABT-378/100 mg ritonavir (3 capsules) twice a day. The other 29 patients received 533 mg ABT-378/133 mg ritonavir (4 capsules) twice a day.

The average viral load at study entry was 39,000 copies in the group receiving the standard dose and about 25,000 copies in the patients on the increased dose. The two groups had similar CD4 counts. After six months, seven patients had discontinued because of side effects or treatment failure. Of those who remained on treatment, 92% (23/25) of patients taking the increased dose and 80% (20/25) of patients taking the standard dose were undetectable. The most common drug-related adverse events of at least moderate severity were diarrhea and weakness, and the most common lab abnormality was increased blood fats.

Side Effects of Hydroxyurea

Results from the 3D study were also presented at Durban. This study tested the safety and effectiveness of Sustiva (DMP-266) + ddI + d4T, with or without hydroxyurea (HU). About 150 patients enrolled in the study, 98 who were treatment naïve and 47 who were treatment experienced. The study objectives were to determine whether adding HU to a treatment regimen added benefit and to evaluate the safety and tolerability of an HU-containing regimen.

The combinations were effective in the treatment naïve patients, with 73% of patients achieving a viral load less than 50 copies after a year. Among the naive patients, there was no viral load benefit to adding HU. Among the experienced patients, it was beneficial to add HU - 76% of experienced patients who added HU compared to 50% of patients who did not receive HU achieved an undetectable viral load.

There was a higher rate of moderate to severe peripheral neuropathy reported in the naïve patients than in the experienced patients. There were also more moderate to severe lab abnormalities in the naïve patients than in the experienced patients. The study was stopped early due to the high rates of toxicities overall.

Treatment Pipeline

Here are some of the latest drugs in development:

ABT-378/r - This protease inhibitor from Abbott is currently being reviewed by the FDA, and should be available by prescription soon. It shows activity against HIV with multiple resistance mutations.

BMS 232632 - This protease inhibitor from Bristol-Myers may be the first once-daily PI.

T20 - This entry inhibitor from Triangle Pharmaceuticals prevents HIV from fusing with a CD4 cell. It does not confer resistance and may be effective in treatment-experienced individuals.

PMPA - This nucleotide inhibitor shows activity against NRTI-resistant virus.

DPC083 - This second generation NNRTI from DuPont shows activity against NNRTI-resistant virus.

Wrapping Up

The International AIDS Conference provides an opportunity for scientists and activists to come together and learn from each other. With continued advocacy and activism, there is a chance that everyone in the world can benefit from the advances in HIV research and treatment. As we prepare to tackle HIV in the new millenium, Durban will be a reference point to remind us how far we've come and how far we have to go.