DURBAN WORLD AIDS CONFERENCE
Durban South Africa
July 9
Reported by Jules Levin

Report 1:

I have spent a lot of time trying to get online. AOL in South Africa is horrible. Here's my first report. A second and third is to follow. The 2nd report is on the Satellites Symposium on HIV in India--very important & interesting. Today in the Abbott Symposium David Ho talked about how no matter if plasma viral load is <50 copies/ml there is low level sequential evolution which evidences low level viral replication. This is not new and I'm not sure if there are any new clinical implications from this info. He suggests more potent therapy may suppress this low level replication and then immune based therapy could possibly be more successful at purging the CD4 memory cell reservoir. At this point in research my attitude is prove it. I'm discoraged about an IBT being able to purge this reservoir. I'd love to see it but prove it.

HCV/HIV Coinfection

One of the studies below suggest:

--the rate of HCV/HIV coinfection can also be high in individuals who did not use IV drugs. Although the prevalence of HCV/HIV co-infection in a patient population with low IV drug use was 17% compared to 60-90% in individuals HIV infected through IVDU, this is compared to the 1.8% HCV prevalence in the overall US population. Of course, it's always possible that the 17% may be due to unreported risk behavior. The study participants could have said they did not use IV drugs when in fact they may have or possibly the incident rate is partially due to snorting or smoking cocaine or crack. But this is the second study I've seen reporting similar information, so it's also possible that HCV can be spread, although at a lower rate, sexually. 

--A swiss study reported below showed 95% of current IVDUs who had HIV also had HCV.

--In one study 7/26 patients on HAART developed life threatening liver disease. In a second study none of 40 patients on HAART developed such a problem.

--On an individual basis, people with HIV should be considered for HCV therapy before HIV therapy. In some cases it may improve safety and response on HAART. 

--The study immediately below reported by Nancy Shulman suggests a point that I think is very important. Although some individuals will not achieve undetectable HCV viral load, an important response may be achievable. Improved histology (improved liver condition) may be enough to improve quality of life, stabilize a person's liver condition, and possibly in combination with interferon maintenace therapy allow that person to be alive and ready for future treatment advances. 

Histologic improvements of liver despite virologic failure of interferon (IFN)+ribavirin therapy in 3 HIV+/HCV+ patients
N. Shulman Stanford University, Division of Infectious Diseases, Stanford, CA 

Background: With improvements in longevity associated with HAART, HCV/HIV coinfected patients are experiencing more HCV-related morbidity and mortality. There are several large ongoing and planned randomized studies of HCV treatment in HIV+ patients. The usual outcomes measured for HCV treatment in studies are HCV viral clearance and ALT normalization, although follow up biopsy data in treatment Ùfailures– in HIV- cohorts show improvements in histology in over 30%.

Methods: In an ongoing treatment trial of IFN alpha, 3 million units TIW + ribavirin 800mg/d , 3 patients with virologic failure at 6 months have received pre- and post-therapy liver biopsies. 1 of the 3 patients received an induction of IFN 5 million units/day for one month before changing to 3 million units TIW. Patients had post-treatment liver biopsies between 1-3 weeks after discontinuing therapy.

Results: All 3 (pt A, B, and C) patients were males ages 44, 47, and 50 with baseline CD4 counts 234, 202, and 779. HCV genotypes were1a, 3a, and 2b, and HCV RNA levels of 16,000,000/ml, 10,000,000/ml, and 250,000/ml. 2 patients had cirrhosis at baseline. None of the 3 had a substantial change in HCV RNA with monthly monitoring. ALT remained at least 2X normal in all patients at all time points measured. Patient B did have a 5-fold reduction in ALT from his baseline. The other two had no significant reductions. Knodell scores improved in all three, 11 to 9, 16 to 13, and 15 to 8. Patient B had an apparent reduction in fibrosis as well. 

Conclusion: As has been shown in HIV- HCV+ patients, treatment of HCV with interferon-based therapy can lead to histologic benefits despite lack of HCV clearance or ALT normalization. Biopsy outcomes should be an important part of future therapeutic trials for these patients.


Risk of mortality, CMV infection and other opportunistic complications in a prospective cohort of advanced HIV-infected patients in the HAART era
B. Roson Hospital de Bellvitge, Feixa Llarga S/N, 08907 l'Hospitalet de Llobregat, Barcelona, Spain, 

Objective: To evaluate the clinical course, emergence of opportunistic complications (OCs) and death in severely immunosuppressed HIV-infected patients in the HAART era.

Methods: From June 1996 to September 1998,118 HIV-infected pts with CD4 counts >100 cells/ml, were included in a prospective follow-up. Every 3 months clinical assessment, retinal exam, CD4 counts, viral load and current therapy were recorded. To determine risk of adverse outcomes, pts were classified in two groups: those who received HAART (any therapeutic regimen including 3 drugs taken for longer than 6 months; group A), and those who did not (gr. B).

Results: Median follow up was 25 months (2-36). Overall, 75 pts (64%) were classified in gr. A and 43 (36%) in gr. B. Main reasons for not receiving HAART were liver disease, intolerance or patients' decision. At baseline, 88 (75%) pts had AIDS, median CD4 count was 30 (1-99)/uL, and median viral load was 4.80 (2.70-5.90) log10 copies/mL; (no differences between groups). Overall, 33/118 (28%) pts presented OCs. Only 3 pts (2%) had CMV infection.

The probability of being free of OCs at 24 months was 78% in gr. A and 51% in gr. B, (P = 0.0025). The probability of being admitted to the hospital at 24 months was 35% and 63%; (P = 0.006), respectively. There were 7 (9 %) and 20 (40%) deaths (P>0.001). Overall, 12/27 (44%) died of liver cirrhosis. Only 2 pts in gr. A died of AIDS related complications while receiving HAART. The probability of survival at 24 months was 92% in gr. A and 53% in gr. B (P>0.001).

Conclusions: Pts who received HAART were at lower risk of opportunistic complications, hospital admissions and death than those who did not. The incidence of CMV infection was very low. Overall, liver cirrhosis was the main cause of death. Nowadays when HAART has notably prolonged survival of HIV-infected pts, efforts to treat and control chronic hepatitis are needed to prevent AIDS-non related deaths in these pts.

HIV is associated with sexual risk and HCV with injection risk among young injection drug users in San Francisco
K.A. Page-Shafer^{1}University of California San Francisco

Purpose of this study is to examine seroprevalence and risk factors for HIV, hepatitis B (HBV) and C (HCV) among young injection drug users (YIDU) in San Francisco.YIDU (>30 years) recruited in 4 neighborhoods were questioned about injection and sexual behaviors, sources of clean needles, knowledge and use of needle hygiene, history of STD and overdose experience. Blood was drawn for HIV, HBV and HCV antibody testing.

312 YIDU participated, 193 (68%) males and 87 (31%) females. Median age was 22 (range: 15-29), and median number of years injecting was 5 (range 0-19). Prevalence of HIV, HBV (core antibody or surface antigen), and HCV was 6%, 29%, and 45%, respectively. 93% of those with HIV infection were co-infected with HCV or HBV. Variables independently associated 'OR ;(95% CI)' with HCV seropositivity were: age (per 5 yr. increase) '2.2;(1.3-43.7)', years injecting (per 5 yr. increase) '2.1;(1-3.5)', injected by a sex partner at initiation '3.9;(1.5-9.9)', ever injected with someone else's used needle '2.5;(1.2-5.2)', bleached last time injected with borrowed needle '0.5;(0.2-0.98)', snorted or smoked cocaine, methamphetamine, or heroin in the prior year '0.4; (0.2-0.8)', injected daily '4.4;(2.4-8.5)', and HBV '3.0;(1.5-6.0)'. 

Impact of HCV infection on HIV progression and survival in the Swiss HIV cohort studies
G. Greub University Hospital, Infectious Disease Division, Lausanne, Switzerland

2766 subjects followed in the SHCS and starting potent ART between 01/01/95 and 03/31/99 were included

1011/2766 (36.6%) HIV+ subjects were HCV co-infected. 511/537 (95.2%) active drug user were HCV+ as compared to 22.4% in other groups.

Prevalence of HCV and HIV co-infection in a patient population with low IV drug use
M. Desyatnik Beth Israel Deaconess Medical Center, Pharmacy Department 

The purpose of this study was to determine the prevalence of HCV co-infection in a population comprised of homosexual and heterosexual patients with a low rate of IV drug use.

Through a retrospective chart review of 138 patients, the number of co-infections was established. HCV infection was determined by either newly positive HCV serology or by documented history of hepatitis C infection.

One hundred thirty eight (138) charts were reviewed. Subjects were 21-63 yrs of age (40.7 +/- 7.4, mean +/-SD) with CD4 counts of 10-1341 cells/mm3 (439 +/- 277), HIV-I RNA of 50-309,000 (14,076 +/- 51,200), and weight of 56-115 kg (76 +/- 13). For 46/138 patients, only pre-HAART data was available. Of the rest, 90 patients were receiving HAART and 2 patients chose not to receive antiretroviral therapy. The overall prevalence of HCV co-infection was 17.4%. Bear in mind the overall HCV infection rate in the USA is about 1.8%.

Anonymous unlinked seroprevalence of HIV and hepatitis C in two emergency departments-using patient databases to distinguish previously diagnosed cases
S. Houston University of Alberta, 2E4.11 Mackenzie Centre, University of Alberta, Edmonton, Albera Canada

3057 subjects were entered in database. Subjects were younger, presented more frequently with trauma and more often went on to admission than the general ED population (all p>0.05). 71% presented with medical illnesses, 21% with trauma. 7% self-identified as aboriginal. 37(1.2%, 95%CI = 1-2)were HIV-seropositive; 2 others demonstrated a banding pattern characteristic of acute seroconversion. HIV infection was associated in multivariate analysis with aboriginal status, age and HCV infection. 27 of all 39 (69%) HIV-infected subjects and both seroconverters were HCV co-infected..

Life threatening hepatotoxicity during combination anti retroviral treatment: Incidence, risk factors and outcome
M. Puoti Clinica di Malattie Infettive, Spedali Civili, P.zzale Spedali Civili, Italy

Objective: To assess the incidence, etiology and outcome of life threatening hepatotoxicity (LTH) during combination antiretroviral treatment (ART).
Design: Prospective cohort study.
Setting: Tertiary care centre.
Patients: Seven hundred fifty five HIV naives seropositives consecutively undergoing combination ART from January 1997 to June 1998.
Interventions: Liver enzymes and liver function tests were tested at the 1st and then at least every 4 months. Liver biopsy and follow up was proposed to all patients with LTH. Main outcome measures: LTH was defined as "de novo" occurrence of liver failure or increase of liver enzymes of at least 10 times over baseline or 5 times if markedly abnormal.
Results: Twenty six cases of LTH were observed with an incidence of 4.2 per 100 person/years. Risk factors for LTH were: history of injection drug use (Odds Ratio, OR 7.6), age younger than 35 (OR 4.7), antibody for hepatitis C and Delta viruses reactivities (ORs 6 and 4.6), baseline abnormalities of liver function tests (ORs 5.1 for hypertransaminasemia, 3.7 for hyperbilirubinemia, and 5.8 for prolonged prothrombin time). Liver histology showed exacerbation of viral hepatitis in all of 16 biopsied patients. Variations of aminotrasferases and CD4 cells were significantly correlated in patients with LTH (correlation coefficient: p>0.001). Death occurred during follow up in 7 out of 26 patients all showing liver failure at occurrence of LTH and baseline CD4 lower than 200/mm3 (vs 42% of pts. alive at 18 months p = 0.01). ART was re-started in the remaining 19 after interferon alpha pre-treatment or 4 months wash out without LTH relapse.
Conclusions: LTH is mainly related to exacerbation of viral hepatitis due to immune restoration that can cause irreversible liver disease in patients with severe immune depletion. Careful monitoring and earlier starting of antiretroviral treatment are priorities in the management of patients with viral hepatitis.

Prospective evaluation of liver damage in a cohort of HIV/HCV coinfected patients treated with protease inhibitors (pi)
Bigli Ospedale Civile ASTI, Italy, 

Background: The role of PI treatment in inducing liver damage in HIV/HCV coinfection is debated. Therefore, we prospectively evaluated virological, biochemical and ultrasonographic (US) parameters of liver damage in a cohort of PI-treated HIV patients with HCV-related chronic active hepatitis (CAH).
Methods: 52 consecutive PI-naive patients, starting HAART for the first time or after a treatment failure, with HCV-related, biopsy-proven CAH, persistent HCV viraemia, and ALT >5x normal value, were enrolled over 90 days. HCV / HIV loads, CD4 counts, ALT, PT, and U.S. hepatic caudate/right lobe ratio (C/RLr) were evaluated monthly and at end of follow-up (FU).  
Results: Forty patients (32 M, 8 F; 10 A1-A2; 21 B2-B3; 9 C3; mean HCV viral load = 4.5±1.7 MEq/mL, HIV load = 3.81±1.9 log c/mL, CD4 count = 320±307/uL, PT = 102±8%, ALT = 92±68 U.I., C/RLr >0,65 at entry) were treated without changing schedule for 87.2±2 weeks (range 85-89,5) with 2 NRTI plus Indinavir (18 pts), Nelfinavir (12 pts) or Saquinavir (10 pts). Mean HCV load, HIV load, and CD4 count at the end of FU were 4.8±1,6 MEq/mL, 2.56±1,8 log copies/mL, and 357±290/uL, respectively (compared to baseline: "p" = 0.05, >0.05 and >0.05 by paired t-test). Liver damage parameters did not change significantly at the end of FU, either in the whole population (respectively, PT = 99±9% ALT = 98±70 U.I., C/RLr >0,65; p = n.s. by paired t-test), or according to clinical stage, HIV load at entry, or the P.I. employed.  
Conclusions: HIV protease inhibitors have been associated with various levels of hepatocellular damage. In this study, performed on a cohort of 40 HIV patients with HCV-related CAH prospectively followed for more than 22 months, long-term antiretroviral treatment including three different IPs does not seem to induce any significant worsening of liver damage or increase in HCV viral load.

Liver Fibrosis progression is related to CD4+ cells depletion in patients with Hhepatitis cand human Iimmunodeficiency virus coinfection
M. Puoti }Clinica Malattie Infettive, University of Brescia, P.zzale Spedali Civili 1, I 25123 Brescia, Italy

Objective: To evaluate the relationship between liver fibrosis observed in Human Immunodeficiency Virus (HIV) seropositive patients with hepatitis C virus (HCV) coinfection and CD4 lymphocyte depletion. 
Design: Evaluation of liver biopsies obtained from intravenous drug users with chronic hepatitis C with or without HIV coinfection. 
Setting: Tertiary care centers. Patients: 204 HCV infected patients, 84 with and 124 without HIV coinfection. 
Interventions: Blind evaluation of the stage of fibrosis according to the METAVIR classification. 
Main outcome measures: The relationship between the stage of liver fibrosis and CD4 levels was analyzed taking into account the variables known or suspected to influence liver fibrosis progression by using polytomous logistic regression. 
Results: Twenty-four patients (11%) showed many fibrous septa with (5%) or without (6%) cirrhosis (group A), 56 (27%) had few fibrous septa and 124 (60%) had no fibrous septa. An association was found between CD4 lymphocyte counts lower than 500/mmc and the presence of many fibrous septa (OR 3.2; p = 0.037), independently from the other factors such as HIV infection, duration of disease, sex and alcohol abuse. 
Conclusions: CD4 cells depletion is independently associated with the severity of liver fibrosis in chronic hepatitis C. Antiretroviral combination therapy aiming at keeping high CD4 counts should be regarded as a priority in the care of HIV and HCV coinfected patients.