Report from the Durban WORLD AIDS CONFERENCE
Durban, South Africa
Tuesday July 11, 2000
reported by Jules Levin

Report 9

Are you Interested? Donate $40 per Month for HAART IN SENEGAL

As I reported earlier, the Senegal government has a program of access to HAART. Normally, HAART costs $800 a month in Senegal, as reported to me. For $40 per month the government supplies a HAART regimen. I met a Senegelese HIV-infected person and I'm considering paying $40 for him. After relaying this story to individuals at this Conference, others have expressed interest in donating $40 monthly for a person in Senegal. If you are interested please contact me by email or by calling the NATAP office (212 219-0106; toll free 888-26.NATAP).

LIVING WITH HIV

David Ho, Tony Fauci

Tuesday's opening plenary session was called Living With HIV and David Ho and Anthony fauci talked about ongoing replication, viral decay in persistent reservoirs, difficulty of achieving eradication, and fauci talked about 2 STI (structured therapy interruptions) studies he is conducting.

Ho started by showing a picture of a virion about to enter a CD4 cell and said this is what causes HIV. Then he said Mbeki should act and reverse his position. The audience applauded. He reviewed the bi-phasic decline of viral load after initiating therapy. Every day half of productively infected CD4 t-cells die off. Virion halflife is 30 minutes and cleared quickly by liver and spleen. He can calculate that 10 million mutant viruses can be produced every day. So many mutations can develop. As we know HIV can be found in an integrated dormant replication competent form in CD4 memory cells and this reservoir persists. This was reported several years ago by Bob Siliciano and others.  This prevents eradication and leads to the need to continue therapy. HIV half-life in reservoir is likely 44 months. Therefore reservoir is likely 60 years or lifelong and unlikely to be eradicated. This reservoir, according to Ho, can decay but very slowly. Others think it doesn't decay. Ho says the means for persistence of virus in this reservoir, despite undetectable virus in plasma when on HAART, replenishment due to ongoing low level replication. That's the bone of contention--that replenishment of the reservoir is the cause of its persistence. So he replication is ongoing and thus he says replenishing this reservoir and causing it's persistence. Others have said that this reservoir simply persists, because drugs don't affect this reservoir. He is claiming replication in blood is ongoing even when viral load is undetectable (<50 copies/ml) in plasma. As I reported, in Sunday's talk he said he believes replication is ongoing because he sees sequence evolution at low level even when viral load in plasma is <50. He also showed tonsil & gut lymphoid tissue pix where virus can be seen, although very little. Other studies have also reported indirect evidence of ongoing low level replication. Thus, even though 99% of virus replication can be stopped with therapy low level replication is ongoing. He sees and has previously reported decay can occur when treatment starts in an early infection (acute infection) selected group (n=8) of HIV infected. My interpretation is that he is theorizing that if you can block 100% of replication you can decay virus from the reservoir and empty it. He is implying to me HIV can be eradicated under these circumstances. I think some would question this conclusion. Ho also said there is no evidence that ongoing replication is due to resistant virus because no genotypic resistance is found. This also has been reported before. He speculated the replication may be due to cellular resistance. He also speculated that something he called space may be the reason for ongoing replication. Spacing is a simple concept. When a person takes one drug penetration or distribution is limited into various tissues, organs, or other parts of the body. When a person takes two drugs penetration & distributtion is improved. And with 3 or more drugs it's improved further. But Ho said even with 3 or 4 drugs penetration or distribution is likely not complete.  At Sunday's talk at the Abbott symposium Ho talked about, as he has previously, how more potent HIV therapy might suppress HIV enough so that immune based therapy may be useful to purge the CD4 memory cell reservoir or to better control HIV. Several drugs including IL-2 have been explored to purge this reservoir of HIV, but without success. The possibility that IBTs might help control HIV remains to be explored better. Possibly the use of one or more vaccines (French vaccine, Remune) may help control HIV after it's fully suppressed with HAART. Possibly, this can be accomplished in conjunction with interruptions.

FAUCI STIs

Fauci discussed 2 studies being conducted at the NIH. They explore the possibility that intermittent therapy and/or periodic interruptions of therapy can be used successfully. Using this therapeutic approach, patients could interrupt therapy and possibly this would prolong usefulness of therapy because maybe it would be easier and more tolerable to take therapy.

Fauci said virus in lymph tissue is continually being bombarded by cytokines. The micro environment in the lymph tissue persists. So after fully suppressive therapy if you stop therapy (3 years) virus can be found when stimulated, and he says its due to this remaining cytokine environment. He reviewed the failed attempt that IL-2 could purge the CD4 memory cell reservoir, referred to above by Ho, of virus, although it appeared that the reservoir may have been reduced by IL-2. Eradication is unlikely. Short & long term side effects and toxicities, and other concerns, make continued therapy over the long term difficult.

He starts talking about STIs. He suggests multiple STIs may reset the viral setpoint but one interruption is not likely to do that. This concept is being explored and suggested by other research--multiple interruptions may reset a person's viral setpoint to a lower level after they interrupt therapy. therefore, maybe they could stay off therapy for a while without danger. Fauci explained that his goal is to provide a situation where people can be on therapy less time. Is intermittent therapy as good as continual therapy?? Fauci discussed his 2 studies. One study is one week and one week off therapy, continually repeated--intermittent therapy. The other study is continual repeats of one month off therapy and 2 months on therapy. All of this is after a person is virologically well suppressed. The concerns include resistance may emerge due to coming off therapy. It appears as though after interrupting therapy viral load ought not to go above the person's original viral load set point. But I think this is also a concern. Viral load may infrequently go back above the original set point. So, the long term safety has not yet been established. Results won't be available for 1 or more years. Fauci said virus will not be able to be controlled permanently off therapy, patients will have to restart therapy, because the immune response causing some viral control (stimulus of CTLs) will where off. So the hopeful goal of the NIH studies is that therapy can be controlled with intermittent or periodic interruption of therapy. This could theoretically lower costs of treatment, improve tolerability and ultimately imrove and prolong viral suppression, make drugs be effective for longer, and prolong life for longer.