Durban World AIDS Conference
Thursday, July 13
Durban, South Africa
Reported by Jules Levin

Report 18

Thursday night at 8:45pm in the press room. The conference is winding down. People are in a celebratory mode on the last night. Today was the last for scientific reports. Tomorrow morning is the closing ceremony where Nelson Mandela will speak and the usual summaries of the science reported here. There is a sense of relief that its over. Many people are gathering and going out to Dinner.

This conference was I think a turning point in how the world will deal with AIDS. It's a milestone in that Durban has put the AIDS crisis in developing countries on the map and minds of people throughout the developing world. Every night on CNN, whose coverage was great as I watched it in my hotel room, Americans were able to hear about the crisis in Africa, about South Africa, Pres. Mbeki, and the awful suffering and deprivation of people with AIDS on this continent. Personally, this experience has very much affected my own thoughts and feelings about this problem. I had decided not to attend this meeting but changed my mind about 1 month ago. It was a very good decision. In Geneva, at the last World Conference, I was only interested in data to bring back to the USA. Here in Durban, I was grabbed by the atmosphere, the people, the suffering, India's problem, and the compelling need to do something. This conference was different than Geneva.  This conference was intimate, the convention center is much more intimate than the one in Geneva. Every day immediately outside the convention center was a series of tents holding food vendors serving all the local fodos you might want. But, I only ate in the hotel. The atmosphere was festive and it appeared to me that everyone was excited to be here and they all felt this was an historical and precedent setting event.

I was one of those people that thought there would not be enough interesting science here but I was wrong. Most people I speak with feel there was a good amount of interesting science. Although some of the science was not well done. There was a good deal of interaction in the science sessions. I leave Durban on Saturday and will be stopping in London for a few days before heading back to NYC (The Big Apple). As I previously mentioned, several researchers are covering Durban for NATAP and you will be receiving reports from them and me. All reports are posted to the NATAP web site for reference.

Hydroxychloroquine/chloroquine (HCQ)+hydroxyurea+ddI: a new economical triple therapy

This presentation was an oral late breaker at today's Thursday late breaker session. There was a good deal of discussion through the earlier days expressing expectation for hearing about this drug for treating HIV. Hydroxychloroquine/chloroquine (HCQ) are inexpensive drugs with anti-HIV activity in vivo. I spoke with the author of this study, N Paton from Tan Tock Hospital in Singapore, and he told me that HCQ has anti-HIV activity in vitro and in humans.. This report relates on their prospective open-label pilot study to evaluate the safety, tolerability and efficacy of the combination of HCQ, hydroxyurea, and ddI. Since the drug is not patented they are looking for funding to conduct future studies. Paton told me HCQ has antiviral activity approximating AZT (0.5 log) and I think it might be worth considering combining it with an abacavir triple NRTI regimen. He said its safe and tolerable.

HCQ and CQ are used for arhtritis and malaria. In vitro studies have shown HCQ/CQ can decrease viral replication. As well, it increases pH in cytoplasmic vesicles, inhibits post-translational modification of gp120, and inhibits IL-6 production. Actually, a funny situation surrounded the presentation on HCQ/CQ. Paton was supposed to deliver the talk but because the times were wrong in the program his slides were there but he was not. So, Brian Gazzard, UK researcher showed his slides but was unable to offer much comment. So he made it quite humorous. However, the slides related the history of HCQ monotherapy trials.

Sperber et al 1995
HCQ vs placebo: HCQ significantly reduced viral load
Sperber et al 1997
HCQ vs AZT. HCQ reduced viral load by 0.38 log at 16/52
Boelaert and Sperber 1998

In vitro: CQ adds to ddI & hydroxyurea (HU) activity

They studied 20 anti-retroviral naÔve patients with viral load  <100,000 copies/ml, CD4 count >150 cells and no opportunistic infections within the previous 6 months. Patients received the combination of hydroxychloroquine (200 mg bid), hydroxyurea, (500 mg bid) and ddI (125/200 mg bid) for 24 weeks. The study was conducted from September 1999 to May 2000. The study was conducted at a single site in Singapore. People were excluded for diabetes, retinal disease, psoriasis, G6PD deficiency, peripheral neuropathy, previous pancreatitis, hepatotoxic medication, LFTs >3 x ULN, hemoglobin <10g/dL, neutrophils <1000, platelets <120,000. The following labs were monitored: FBC, UEC, LFT, PT/PTT, amylase, glucose, fasting cholesterol, triglycerides, opthalmology exam, viral load, and CD4s. There were23 eligible patients recruited. 6 withdrew (non-compliance). 17 completed the study (13 Chinese, 2 Indian, 1 Thai, 1 Malay; 16 stage A, 1 stage B disease). The median age was 34.

VIRAL LOAD. Baseline viral load was 21,848 copies/ml (3892-81,394), CD4 242 (167-414). At week 12, 5 patients (29%) had undetectable viral load (<400 copies/ml). The mean viral load reduction was 1.27 log. At week 24, 6 patients (35%) had undetectable viral load and the mean viral load reduction was -1.23 ± 0.58 log.

CD4s. The CD4 change at week 12 was +28 (±134) at week 12, and 64 at week 24 (±120). The CD4 percent change was 4.3 (±5.7) at week 12 and 5.5 (±5.6) at week 24. The CD8 change was -192 (±267) at week 12, and -163 (±307) at week 24. The CD8 percent change at week 12 was -8.8 (±4.2) at week 12 and -10.5 (±7.8) at week 24.

ADVERSE EVENTS: diarrhea 11, cough 9, fatigue 8, pruritis 6, dry skin 5, fever 5, anorexia 5. There were 2 grade 3 AEs: neutropenia and increased amylase. Grade 2: 2 nutropenia, 2 thrombocytopenia, 1 increased AST, 1 increased bilirubin, 2 increased amylase, 1 increased glucose.Grade 1: 1 anemia, 8 nuetropenia, 5 increased ALT, 2 increased AST, 2 increased bilirubin, 5 increased amylase. There was 1 grade 1 peripheral neuropathy, and 2 unrelated serious AEs: haematesis, liver absecess.

Paton concluded the drug to be safe and well tolerated, moderately effective:

Due to poor access to treatment in developing countries and limited resources to buy drugs, the authors are planning a study in Uganda. Itís a pilot phase Iib randomized placebo double blinded study to last 8 weeks. 40 patients will receive 600mg chloroquine phosphate or placebo daily and will be evaluated every 2 weeks for adverse events, immunologic & virologic markers. Labs and opthalmologic exams will also be monitored.