12,500 people attended the XIII International AIDS Conference in Durban,
South Africa, on July 9-14, 2000. The title was "Break the Silence,"
a theme that was woven throughout the conference. Attendees included
physicians, researchers, other health professionals, policy makers,
and persons living with HIV or AIDS representing more than 178 countries.
In addition, there were more than 1,000 volunteers.
This was the first time that the biannual international AIDS conference
occurred in a resource-poor or developing country; all others have been
hosted in North America, Europe, or Japan. The location is particularly
important, given that approximately three-fourths of the estimated 34
million persons with HIV or AIDS worldwide live in sub-Saharan Africa
(figures are as of December 1999). The HIV/AIDS epidemic is particularly
severe in South Africa, where approximately four million people are
HIV positive, including one-fourth to one-third of all pregnant women.
More than 5,000 abstracts were presented, including 14% in oral presentations,
10% in oral poster presentations, and the remaining 76% in standard
There were five scientific tracks: Basic Science; Clinical Science;
Epidemiology, Prevention, and Public Health; Social Science; and Rights,
Politics, Commitment, and Action. At any one time, up to 13 concurrent
sessions took place. Many oral sessions are available at www.webcast.aids2000.com
. This program is sponsored by Gilead Sciences.
The conference was organized by five groups: the Global Network of
People Living with HIV/AIDS (GNP+), the International AIDS Society (IAS),
the International Council of AIDS Service Organizations (ICASO), the
International Community of Women Living with HIV/AIDS (ICW), and the
Joint United Nations Programme on HIV/AIDS (UNAIDS). There were 13 principal
sponsors: Abbott Laboratories, Agouron Pharmaceuticals, Boehringer Ingelheim,
Bristol-Myers Squibb, Glaxo Wellcome, DuPont Pharmaceuticals, Merck
Sharp & Dohme, Roche, Pharmacia & Upjohn, Dimension Data, Cisco
Systems, Dell E Com, and Microsoft. Other sponsors included the Department
of Health of South Africa, the U.S. National Institutes of Health (NIH)
Office of AIDS Research (OAR), Gilead Sciences, the Ford Foundation,
Trimeris, and Bayer Diagnostics.
There was much controversy surrounding the Durban conference in the
months before it took place. Issues included safety concerns for attendees,
a threatened boycott by potential attendees, and South African President
Thabo Mbekis statements denying that HIV is the cause of AIDS. While
the first two concerns essentially did not materialize, President Mbeki
and his statements continue to detract from much of the real issues
of this pandemic in the year 2000. Notwithstanding, the conference overall
was remarkable, given the perspectives and inspiration from African
Events that took place before the conference added to the controversy.
Several thousand physicians, scientists, and other researchers signed
the so-called Durban Declaration affirming that HIV is the cause of
AIDS; the document was published in the journal Nature. Also, in the
afternoon before the opening ceremony, approximately 4,000 protestors,
including persons with HIV/AIDS, participated in a rally in downtown
Durban demanding access to anti-HIV drugs in resource-poor countries.
Former South African First Lady Winnie Madikizela-Mandela was a speaker
The keynote speaker at the opening ceremonies was South African President
Thabo Mbeki. Even though he did not claim or deny that HIV is the cause
of AIDS, he did use the terms "HIV" and "HIV/AIDS"
several times during his speech. Having encountered fringe scientists
on the Internet as well as so-called HIV deniers, President Mbeki decided
that other social and health issues need to be considered in countries
like South Africa. Such concerns include the poverty and malnutrition
that continue to separate relatively wealthier countries of the north
(and west) from those in sub-Saharan Africa. Many are concerned because
the South African presidents stance allows him to deny access of anti-HIV
therapy to many South Africans with HIV, including pregnant women.
One of the high moments of the conference was the closing speech by
former South African President Nelson Mandela, who received a standing
ovation. Mr. Mandela emphasized, "We need to break the silence,
banish stigma and discrimination, and ensure total inclusiveness within
the struggle against AIDS. Let us combine our efforts to ensure a future
for our children. The challenge is no less."
Nelson Mandela Foundation. Closing address at the XIII
International AIDS Conference.
President Thabo Mbeki. Opening ceremony at the XIII
International AIDS Conference.
National Institutes of Health (NIH) Researchers Describe Treatment Interruption Strategy
One of the more interesting groups of presentations in Durban was in
the area of highly active antiretroviral therapy (HAART) interruptions.
The research included presentations by NIH researchers Mark Dybul, MD,
and Anthony Fauci, MD, Head of the U.S. National Institute of Allergy
and Infectious Diseases (NIAID). Dr. Dybul describes their research
in this issue of BETA.
Dybul, M. and others. Short cyclic intermittent HAART:
a pilot study. Abstract and late-breaker oral presentation LbOr12.
Fauci, T. Host factors in HIV disease. Abstract and
oral plenary presentation TuOr36.
Decreasing AIDS Progression and HIV Transmission in Resource-Poor Countries
Several presentations addressed potential mechanisms for decreasing
HIV disease progression in resource-poor countries. Strategies are based
upon the observations that many AIDS-related opportunistic infections
(OIs) increase HIV RNA viral load, which in turn may increase HIV disease
progression and AIDS death rates. Therefore, treating OIs -- which is
often not done in resource-poor countries -- would be expected to decrease
HIV disease progression, decrease AIDS death rates, and likely decrease
HIV transmission rates. Mauro Schechter, MD, from Brazil discussed one
example: TMP-SMX (Bactrim, Septra, cotrimoxazole) to treat and help
prevent PCP (Pneumocystis carinii pneumonia) and several other bacterial
infections. In his plenary presentation called "Advances in Treatment
of AIDS," Dr. Schechter reviewed statistics from several countries
and regions that showed a decline of AIDS-related deaths before the
advent of HAART that included a protease inhibitor (PI) or non-nucleoside
reverse transcriptase inhibitor (NNRTI) drug. That decline is at least
partly due to wider use of antibiotics to treat and prevent OIs in AIDS.
In another presentation, Dr. Z. Bentwich and colleagues from Kaplan
Medical Center in Rehovot, Israel, expanded their previous reports about
"deworming." Dr. Bentwichs team evaluated Ethiopians who
had immigrated to Israel, many of whom had chronic worm infection (helminth
infestation) of their intestinal tracts (colon), HIV infection, or both.
They found that immune cells from Ethiopians with intestinal worms and
without HIV infection were more susceptible to HIV infection in laboratory
tests. This was due to immune system activation associated with a higher
level of CCR5 receptors (which HIV uses to enter cells) and a lower
level of beta chemokines (intercellular messengers that decrease the
risk of cellular HIV infection). Eggs in the stools of Ethiopians with
worm infestation and HIV infection significantly correlated with higher
HIV viral loads in blood plasma. In addition, HIV RNA decreased significantly when the worms were effectively
treated. The authors concluded that helminthic infestation and immune
activation "account for rapid spread [transmission] and progression
of HIV infection in helminthic-infested regions and will probably undermine
HIV vaccine success." They also claimed that "eradication
of helminths is feasible, can be applied in Africa and the developing
world, and [may] have far-reaching impact on the AIDS epidemic."
Treating intestinal worms would likely decrease HIV transmission rates
by the sexual route and from mothers to their newborns. Most of the
drugs used to treat intestinal helminths are generic and relatively
Bentwich, Z. and others. Helminthic infections have
a major impact on pathogenesis of AIDS and development of HIV protective
vaccines in Africa and the developing world. Abstract and late-breaker
Schechter, M. Advances in treatment of HIV/AIDS. Abstract
and plenary oral presentation TuOr37.
Marijuana Use Does Not Increase Viral Load
Results of the first government-sponsored study of marijuana effects
in persons with HIV were presented in Durban. The results showed that
three weeks of smoking a marijuana cigarette three times daily does
not increase HIV viral load in persons taking HAART. The randomized,
placebo-controlled, and partially blinded study compared inhaled (smoked)
marijuana with oral dronabinol (Marinol 2.5 mg, a synthetic pill with
active marijuana derivative) and oral placebo (inactive drug), each
three times daily before meals. The marijuana was supplied by the U.S.
government, which also funded the study. The lead author was Donald
I. Abrams, MD, of the University of California, San Francisco (UCSF).
The PI used was either indinavir (Crixivan) or nelfinavir (Viracept).
Sixty-seven subjects (4% women, 6% male-to-female transgender, 52%
non-White) enrolled and remained in a clinical research center for 21
days of the study. Two-thirds were older than 40. The median baseline
CD4 cell count was 300 cells/mm3, with a median
HIV RNA less than 50 copies/mL. A prior AIDS OI had occurred in 49%.
After the three-week study, the inhaled marijuana group had a mean
viral load decrease of -0.15 log, the dronabinol group had a -0.19 log
decrease, while the placebo arm had a 0.06 log copies/mL increase (in
an "as treated" analysis, including only those participants
who completed the study). None of these changes are statistically significant.
In 50-55% of each arm, there was no significant change in viral load.
CD4 cell count changes and other parameters are pending. There was a
93% completion rate. Weight gains occurred in all three arms: inhaled
marijuana (3.5 kilograms, or kg); dronabinol (3.2 kg); and placebo (1.3
kg). (Kilogram weight divided by 0.454 equals weight in pounds, or lbs.)
This is the first study that has shown a weight gain resulting from
There were three adverse events in the inhaled marijuana arm: one subject
had moderate neuropsychiatric symptoms (this person chose to leave the
study), one subject developed moderate tachycardia (fast heart beat;
the subject remained on study), and one subject developed severe neuropsychiatric
symptoms (treated with lorazepam [Ativan] antianxiety drug; the subject
remained on study). In the drona-binol arm, there were four adverse
events: one subject developed moderate neuropsychiatric symptoms (the
subject chose to leave the study), one person had moderate headache
and nausea (the subject chose to leave the study), one subject had kidney-area
pain, possibly related to indinavir (possible a kidney stone; the event
was not related to dronabinol and the subject remained on study), and
one subject died two months after the study from hemorrhage (bleeding)
due to portal hypertension (high blood pressure in the portal vein leading
to the liver, usually due to cirrhosis or liver scarring; all unrelated
to dronabinol). There were no adverse events in the placebo arm.
Other analyses about participants in this study are pending. The viral
load results are only short-term. It is possible that longer-term effects
might not be as favorable in terms of viral load. The benefits of inhaled
marijuana (decreased nausea, increased appetite, and weight gain) must
be balanced against the documented side effects. These include an increase
in respiratory infections, decreased immune system function, and a decrease
in short-term memory.
Abrams, D.I. and others. Short-term effects of cannabinoids
on HIV-1 viral load. Abstract and late-breaker poster presentation LbPeB7053.
Fusion Inhibitor T-20 Shows Benefits
Forty-eight-week results of T-20 in treatment-experienced subjects
were presented in Durban by Cal Cohen, MD, of the Community Research
Initiative in Boston. The late-breaker poster showed that one-third
had at least a 1 log reduction in viral load and that no participant
withdrew due to side effects of T-20. A total of 71 persons (8% women,
20% non-White) were enrolled. Subjects added T-20, 50 mg self-injected
twice daily, to a new anti-HIV drug regimen that was based on drug resistance
Study T20-205 was a Phase II, open-label, "rollover" (from
other T-20 studies) trial. The baseline, median number of prior anti-HIV
medications was ten, and 80% of participants had previously taken at
least one drug from each of the first three anti-HIV drug classes. Prior
PI therapy was taken by 79% of enrollees. The median baseline viral
load was 4.8 log (63,095) copies/mL with a CD4 cell count of 133 cells/mm3.
Forty-one subjects (58%) remained on study at the end of 48 weeks. Yet
none of the 42% who discontinued did so due to adverse events related
The results showed the following, using a strict "intent-to-treat"
analysis (all enrollees included). An undetectable HIV RNA viral load
(limit 50 copies/mL) was achieved by 13%. Another 10% had between 50
and 400 copies/mL, while yet another 10% had greater than a 1 log (10-fold)
reduction in viral load and were at a level greater than 400 copies/mL.
Among those still remaining on study, the mean decrease in viral load
at 48 weeks was approximately -1.3 log copies/mL (note that a decrease
is associated with decreased HIV disease progression). Among the 30
subjects who discontinued, 14 (20% of total) did so due to minimal HIV
RNA reduction (less than -0.5 log copies/mL), seven (10% of total) voluntarily
withdrew from study, three (4%) withdrew due to adverse events unrelated
to T-20, and two (3%) were nonadherent to dosing. CD4 cell count changes
were not reported.
Reported adverse events included mild-to-moderate injection site reactions
in 71%, while 21% had severe adverse events possibly related to T-20.
Serious adverse events possibly related to T-20 occurred in 10%. These
included increased liver enzymes (alanine aminotransferase [ALT], alanine
aspartate transferase [AST], and/or gamma glutamyl transpeptidase [GGT]),
altered mental state, anemia (low red cell count), increased amylase
(a pancreatic enzyme) or neutropenia (low white cell count). In a separate
presentation, Joe Eron, MD, of the University of North Carolina at Chapel
Hill reported that participants in the study viewed injection of T-20
as convenient, with little distraction from their daily activities.
T-20 is the first drug in the class of fusion/entry inhibitors. Even
though the viral load results in this study are less than stellar, this
drug appears promising for highly treatment-experienced participants.
T-20 is under development by Trimeris and Roche.
Cohen, C. and others. 48-week analysis of patients receiving
T-20 as a component of multidrug salvage therapy. Abstract and poster
Eron, J. Entry inhibitors: the next frontier in HIV
therapy. Satellite symposium.
Lopinavir/Ritonavir (Norvir) plus Either Efavirenz (Sustiva) or Nevirapine (Viramune) and Two NRTIs
Several presentations focused on the double-PI drug formulation lopinavir/ritonavir
(ABT-378/r, or Kaletra) in combination therapy. [Ed. note: Kaletra was
approved by the FDA this past September.]
The benefits of lopinavir/ritonavir combination therapy in so-called
salvage therapy were presented for persons who had a detectable HIV
viral load despite taking a second PI drug. The doses of lopinavir/ritonavir
twice daily were 400/100 mg (three capsules) or 533/133 mg (four capsules).
The regimen also included efavirenz (a non-nucleoside reverse transcriptase
inhibitor) plus two new NRTI drugs. Study subjects (21% women and 12%
non-White) had never taken NNRTI drugs. The lead author of Study M98-957
was Nathan Clumeck, MD, from St. Pierre University Hospital in Brussels,
For the 29 participants taking the 400/100 mg lopinavir/ritonavir dosing,
the mean baseline HIV RNA was 4.6 log (39,810) copies/mL with a CD4
cell count of 230 cells/mm3. For the 28 participants
taking the 533/133 mg dosing, the mean baseline viral load was 4.4 log
(25,118) copies/mL, with a CD4 cell count of 325 cells/mm3.
Results of the Phase II study were available up to 24 weeks. Even though
the 57 participants had taken an average (mean) of three prior PIs at
study entry, 69% (400/100 mg arm) to 82% (533/133 mg arm) achieved an
undetectable HIV RNA viral load. (Results were with a lower limit of
400 copies/mL and a strict intent-to-treat analysis, which includes
all enrolled subjects.) The mean CD4 cell count increase was 48 cells/mm3
in the 400/100 mg arm and 41 cells/mm3 in the 533/133
At baseline, 43% of the 57 participants had an HIV isolate (strain)
that had at least a 10-fold decreased susceptibility (resistance) to
lopinavir, when compared with the EC50 (effective
inhibitory concentration for 50% of viruses) of wild-type, or nonresistant,
HIV. Baseline HIV isolates from 68% of participants had at least a 4-fold
increase in the EC50 (i.e., decreased susceptibility
or resistance) to at least three PI drugs. Phenotypic resistance testing
was performed using the PhenoSense HIV test from ViroLogic. (A phenotypic
drug resistance test measures the ability of a persons HIV isolate
to grow in the presence of each anti-HIV drug. The protease and reverse
transcriptase genes from the individuals isolate are inserted into
a laboratory isolate before testing.)
The most common adverse events that were at least moderate (grade 2
or higher) included diarrhea (7% in the 400/100 mg arm and 14% in the
533/133 mg arm) and weakness, or asthenia (also 7% in the 400/100 and
14% in the 533/133 mg arm). In the 400/100 and 533/133 mg arms, respectively,
severe or life-threatening (grade 3 or 4) laboratory events included
increases in the following: glucose greater than 250 mg per deciliter,
or mg/dl (10% and zero); ALT greater than five times the upper normal
limit (zero and 4%); total cholesterol greater than 300 mg/dl (28% and
36%); triglycerides (lipids or fats) greater than 750 mg/dl (31% and
36%); and amylase greater than twice the normal upper limit (zero and
7%). However, the ratio of total cholesterol to HDL (high density lipoprotein
or "good") cholesterol was not significantly changed in either
arm, when compared with baseline (another measurement of heart artery
disease risk). In each of the two study arms, a grade 3 or 4 decreased
neutrophil (white blood cell) count (below 750 cells/mm3)
occurred in 7%.
There were seven total discontinuations (12%) before 24 weeks in both
arms. Two subjects in each arm discontinued due to adverse events, including
central nervous system (CNS) side effects in two persons, stomach-colon
("GI") problems in one subject, and lactic acidosis (likely
due to the NRTI drug[s]) in another subject. Two participants in the
400/100 mg arm and one in the 533/133 mg arm discontinued due to virologic
"failure" (detectable HIV RNA).
Dr. Clumeck concluded that the five-drug combination of lopinavir/ritonavir,
efavirenz, and two NRTIs showed significant potency after 24 weeks in
this small study of persons who had prior multi-PI-drug experience and
who were naive to NNRTIs. It is noteworthy that the percentage of persons
in each study arm that achieved viral undetectability is higher than
in many studies of treatment-naive persons. Part of this would be due
to the high inhibitory quotient of lopinavir, defined as the trough
(lowest) drug level (of lopinavir) achieved divided by the EC50
(see above) of the individuals HIV isolate.
Dr. Clumeck also reported that lopinavir drug levels are decreased
when the Kaletra 400/100 mg formulation is combined with efavirenz,
as compared with lopinavir/ritonavir (same dose) without efavirenz.
Specifically, the trough lopinavir concentration is reduced by approximately
33%, while the AUC (area-under-the-curve, or total drug exposure) concentration
is decreased approximately 25%. The maximal, or peak, concentration
change was not reported. However, when the experimental 533/133 mg dose
of lopinavir/ritonavir was combined with efavirenz, the lopinavir concentrations
achieved were similar to those taking the 400/100 mg dose without efavirenz.
The drug levels of efavirenz in the current study were reported to be
the same in both study arms. Due to the viral load results and drug
interaction studies, the authors reported that all ongoing participants
subsequently have been placed on the 533/133 mg dose of lopinavir/ritonavir
There are some limitations in these results. It would have been helpful
to see the rates of HIV undetectability using an ultrasensitive test.
The CD4 cell increase was not spectacular, but will likely continue
to increase among those who remain in the study and who have persistently
undetectable viral loads or who maintain lower levels than baseline.
Of some concern were the rates of severe or life-threatening increases
in cholesterol and triglycerides in approximately one-third of subjects,
even though there was little change in the overall total cholesterol/HDL
cholesterol ratio. It would be helpful if drug interaction studies could
be performed using one or more of the "statin" drugs (used
to treat high cholesterol) and lopinavir/ritonavir, with and without
efavirenz. The intent would be to ensure that drug levels are not altered
Study M97-765, also presented in Durban, concerned lopinavir/ritonavir
in persons with a detectable viral load after taking their first PI
combination. The regimen also included nevirapine and two NRTIs. The
lead author was Melanie Thompson, MD, from the AIDS Research Consortium
Participants, comprising 70 HIV positive persons (10% women, 34% non-White),
had to have been naive to NNRTIs and to at least one NRTI that was included
in the new regimen. Dosing was lopinavir 400 mg/ritonavir 100 mg (for
36 subjects) or 400/200 mg (for 34 subjects). The median baseline HIV
RNA for the 70 participants was 4.0 log (10,000) copies/mL with a CD4
cell count of 349 cells/mm3.
The 72-week results were as follows. Using a strict intent-to-treat
analysis (including all study enrollees), 57% achieved an undetectable
viral load (limit 50 copies/mL). Using a lower limit of 400 copies/mL,
73% had an undetectable viral load. However, it was reported that among
the 24 participants who had a detectable viral load at week 72, half
of them could be explained by "documented noncompliance, early
discontinuation, or interruption of therapy." Five additional subjects
who had a detectable viral load (limit 50 copies/mL) did have fewer
than 400 copies/mL. The mean CD4 cell increase was 154 cells/mm3.
Baseline phenotypic drug resistance information was available for 81%
of participants. Among those, 63% had at least a 4-fold decreased susceptibility
(resistance) to their previously used PI drug. Phenotypic drug resistance
testing was performed using the Antivirogram test from Virco.
The most common adverse events classified as moderate or worse were
similar to those in the first lopinavir report above. Those included
diarrhea (more than three loose stools daily) in 23%, abnormal stools
(three or fewer loose stools daily) in 4%, nausea in 4%, asthenia (weakness)
in 6%, headache in 1%, and vomiting in 1%. Laboratory abnormalities
that were severe or life-threatening (grade 3-4) included increases
in the following: cholesterol greater than 300 mg/dl (28%); increased
triglycerides greater than 750 mg/dl (25%); GGT greater than five times
the upper normal limit (28%); ALT greater than five times the upper
normal limit (14%); and AST greater than five times the upper normal
limit (9%). Cofactors that might have contributed to the increase in
liver enzymes, including infection with HCV or HBV, were not reported.
The discontinuation rate was 17%, including 4% due to adverse events
and 13% due to other reasons (unrelated to viral load). The three participants
who discontinued due to adverse drug-related events included two due
to gastrointestinal (stomach-colon) symptoms and one due to rash that
might have been caused by efavirenz. Nine participants discontinued
for other reasons, including myocardial infarction (heart attack) in
one subject on day 1 of the study (therefore unrelated to the study
medications), personal reasons, nonadherence, lack of participation
in follow-up, and death due to lung cancer or rhabdomyolysis (destruction
of muscle cells) leading to kidney failure.
These results demonstrate significant potency of the regimen containing
lopinavir/ritonavir plus nevirapine and two NRTI drugs for those participants
with a detectable viral load who were taking their first PI drug combination
and who had never taken an NNRTI. As with all regimens, maximal adherence
to dosing is a key factor in viral load undetectability.
Clumeck, N. and others. ABT-378/ritonavir (ABT-378/r)
and efavirenz: 24-week safety/efficacy evaluation in multiple PI-experienced
patients. Abstract and poster presentation TuPeB3196.
Kempf, D. and others. Identification of clinically relevant
phenotypic and genotypic breakpoints for ABT-378/Ritonavir in multiple
PI-experienced, NNRTI-naïve patients. 4th
International Workshop on HIV Drug Resistance and Treatment Strategies.
Sitges, Spain. June 12-16, 2000. Abstract and oral presentation 89.
Sun, E. New frontiers in antiretroviral therapy. Satellite
symposium sponsored by Abbott Laboratories.
Thompson, M. and others. Analysis of duration of virologic
response in two phase II studies of ABT-378/ritonavir (ABT-378/r) at
72 weeks. Abstract and poster presentation TuPeB3197.
The final, 48-week results of the Atlantic Study were presented in
a late-breaker poster in Durban. This study combined a backbone of two
NRTIs, d4T (Zerit) and ddI (Videx), with a third drug. The third drug
was either nevirapine (an NNRTI), indinavir (a PI), or 3TC (Epivir,
an NRTI ). Overall, the results showed a better outcome in the nevirapine-
and indinavir-containing arms, as compared with the 3TC-containing arm.
The lead author was Kathleen Squires, MD, of the University of Alabama
This open-label and randomized study enrolled 298 (20% women) HIV positive,
treatment-naive persons. Entry criteria were a CD4 cell count greater
than 200 cells/mm3, a viral load greater than 500
copies/mL, and no prior HIV-related symptoms. Standard dosings were
used for all medications except ddI and nevirapine, which were dosed
At baseline, the median HIV RNA viral load was 4.3 log (17,782) copies/mL
with a CD4 cell count of 406 cells/mm3. A high baseline
viral load (greater than 100,000 copies/mL) was detected in 13% of participants.
Baseline characteristics were relatively equal among the three study
Results after 48 weeks revealed the following. Using a strict intent-to-treat
(ITT) analysis, an undetectable viral load (limit 50 copies/mL) was
achieved in 49% of both the nevirapine- and indinavir-containing arms
and in 40% of the 3TC-containing arm. The differences when comparing
any two of the arms were not statistically significant. However, using
an on-treatment analysis (excluding drop-outs), there was a significant
difference when comparing the indinavir- and 3TC-containing arms, with
a trend towards a significant difference when comparing the nevirapine
and 3TC-containing arms. There was no significant difference when comparing
the nevirapine- and indinavir-containing arms. The median CD4 cell count
increase was approximately 140 cells/mm3 in the
nevirapine- and indinavir-containing arms and approximately 160 cells/mm3
in the 3TC-containing arm.
In a separate analysis, Dr. Squires evaluated the viral load response
for those with a high baseline level in the upper quartile, or greater
than 58,519 copies/mL. In an ITT analysis, the percentage with an undetectable
viral load (limit 50 copies/mL) was 48%, 28%, and 26% in the indinavir-,
nevirapine- and 3TC-containing arms, respectively; however, the differences
were reported as insignificantly different. In an on-treatment analysis,
the percentage undetectable was 80%, 56%, and 42%, respectively for
the same three arms, with a trend towards a statistically significant
difference. There was no reported information about adhering to dosing
Adverse events were reported as including all grade 1-4 effects (mild
to life-threatening) that occurred among at least 5% of enrollees. (Note
that most other studies usually do not report mild adverse events, so
the following percentages may appear to be high.) Gastrointestinal side
effects occurred among 74%, 48%, and 53% of the indinavir-, nevirapine-
and 3TC-containing arms, respectively. These included nausea/vomiting
in 31%, 19%, and 17%, and diarrhea in 25%, 15%, and 13%. Rash or redness
of the skin occurred in 4%, 12%, and 0%. Numbness or tingling (neuropathy,
paresthesia) occurred in 10%, 15%, and 15%. Systemic effects (assumed
to be malaise, weakness, and/or flu-like symptoms) occurred in 32%,
24%, and 21%. Discontinuations due to drug toxicities were reported
to be no different in the three arms, without percentages given.
Abnormal laboratory tests were not reported. However, an interim analysis
of the first 235 participants (79%) who completed 48 weeks was presented
at last years 39th Intersci-ence Conference on
Antimicrobial Agents and Chemotherapy (ICAAC). Severe or life-threatening
adverse events at that time revealed nothing surprising that had not
been reported previously for each of the study drugs. In the indinavir-containing
arm, 5% of subjects developed a kidney stone(s). Severe or life-threatening
laboratory toxicities were as follows: increased liver enzymes occurred
in 5%, 13%, and 6% of the indinavir-, nevirapine-, and 3TC-containing
arms, respectively. Increased amylase occurred in 4%, 4%, and 7%.
Twenty-five percent of participants in the indinavir arm, 17% in the
nevirapine arm, and 29% in the 3TC arm discontinued the study early
as of that preliminary analysis. Adverse events were responsible for
42% of study discontinuations. Other common causes for discontinuation
included participant request or lack of participation in follow-up.
The interim results had been presented by Robert L. Murphy, MD, of Northwestern
University in Chicago.
Results of the Atlantic Study after one year indicate that a regimen
with three NRTIs that includes 3TC, ddI, and d4T does not perform as
well as triple therapy arms that included ddI and d4T with either nevirapine
or indinavir. Those two latter arms performed rather similarly, with
a trend towards a better outcome for those with a high baseline viral
load (greater than 58,519 copies/mL) that favored the indinavir-containing
arm. The adverse event profile of each arm was somewhat different, reflecting
known side effects for the drugs used. All three regimens were similarly
well tolerated with no significant differences in discontinuation rates
when comparing the three arms. This study is ongoing and will continue
for a total of roughly three years (144 weeks).
Murphy, R.L. and others. The Atlantic Study: a randomized,
open-label trial comparing two protease inhibitor (PI)-sparing antiretroviral
strategies versus a standard PI-containing regimen, 48 week data. 39th
Interscience Conference on Antimicrobial Agents and Chemotherapy. San
Francisco. September 26-29, 1999. Abstract and late-breaker oral presentation
Squires, K. and others. The Atlantic Study: a randomized,
open-label study to evaluate the efficacy and safety of three triple-combination
therapies aimed at different targets in anti-retroviral naïve HIV-1
infected patients, final 48 week analysis. Abstract and late-breaker
poster presentation LbPeB7046.
Two hundred fifty-nine abstracts (5% of the total) addressed adherence
to dosing of anti-HIV medications. This is an extremely important issue
in terms of achieving and maintaining an undetectable viral load. However,
100% adherence is very difficult for many people, particularly after
a prolonged period of taking medications.
Interim results of one presentation highlighted the ease and preference
of twice-daily dosing of medications, as compared with three-times-daily
dosing. Specifically, researchers from the NICE study (M99-047) have
reported that persons who switch to a double PI combination with indinavir
and ritonavir (400 mg of each twice daily) plus two NRTIs prefer that
regimen and are more adherent to medication dosing. Before switching,
participants were taking standard indinavir dosing of 800 mg three times
daily plus two NRTI drugs. When compared with the nonswitched arm of
the randomized, controlled study, those who switched were significantly
more likely to report that 1) it was easier to take their PIs as prescribed,
2) they missed fewer doses, 3) the new regimen was easier to take at
the same time each day, and 4) it was easier to coordinate dosing with
meals. The presenting author was Edwin DeJesus, MD, from the IDC Research
Initiative in Altamonte Springs, FL.
The NICE study has planned to enroll a total of 500 participants who
are taking standard three-times-daily indinavir (800 mg) plus two NRTIs
and who have an undetectable HIV RNA viral load (using a test used at
a practitioners local laboratory). Four hundred subjects will be randomized
to switch to twice-daily indinavir/ritonavir (400/400 mg) plus two NRTIs,
while the other 100 subjects will be randomized to maintain their current
regimen. Those in the switching arm may take their medications without
meal restrictions or fluid requirements. After 12 weeks of the study,
participants may cross over to either arm, depending upon individual
or physician preference. The 400 mg twice-daily dosing of indinavir/ritonavir
has been associated with an extremely low rate (i.e., only in rare anecdotal
cases) of kidney stones -- a significant side effect of indinavir that
still occurs with other dosing (indinavir 800 mg/ritonavir 100-200 mg,
each twice daily, or mono-PI drug therapy with indinavir).
At the time of interim analysis, 215 participants randomized to the
switching arm and 60 participants randomized to the nonswitching arm
had completed four weeks of the study. Among all randomized subjects,
7-17% were women and 30-40% were non-White. The mean baseline CD4 cell
count was 558-572 cells/mm3. As indicated, all participants
had an undetectable viral load at baseline.
Those who completed four weeks were given a standardized "Medication
Taking Survey." One question in the survey was "In the past
two weeks, on a [Likert] scale of 1 ("very easy") to 5 ("not
easy"), how easy has it been for you to take your PI medicine as
prescribed?" Significantly more persons in the switching arm reported
"very easy" after four weeks (59%) compared with baseline
(48%), as compared with the nonswitching arm (52% after four weeks and
at baseline, i.e., no change).
Another question was "In the past two weeks, how many times do
you think you missed taking your PI medication?" Significantly
more persons in the switching arm reported "none" after four
weeks (73%) compared with baseline (62%), as compared with the nonswitching
arm (57% after four weeks and 52% at baseline, i.e., a 5% increase).
Also, after four weeks 98% of the switching arm reported zero, one,
or two doses missed, as compared with 90% of the nonswitching arm.
Yet another question was "In the past two weeks, when did you
miss at least one dose of your PI medication?" The three choices
were morning, midday, and bedtime. At baseline, 23% of the switching
arm and 30% of the nonswitching arm indicated that they missed the midday
dose. After four weeks, 4% of the switching arm indicated midday (on
a twice-daily regimen, none should have had a midday dose) with 30%
of the nonswitching arm still indicating midday (i.e., no change). After
four weeks, 26% of the switching arm admitted to missing at least one
dose anytime (in the morning, midday, or at bedtime), compared with
47% of the nonswitching arm.
There were no interim results for viral loads or CD4 cell counts to
correlate with the study questionnaire results. However, the entire
enrollment had not yet been filled.
One potential limitation of the study is that the results are based
upon information reported by participants; this is the case with many
studies measuring adherence. Other studies have shown that reported
adherence by participants is not always the same as adherence measured
by MEMS caps (computerized medication bottle caps that record each time
the container is opened). One way to validate peoples self-reports
would be to measure drug levels in blood (see "Therapeutic
Drug Monitoring"). Regardless, the statistically significant
improvements in adherence issues that were measured in the switching
arm (to twice-daily indinavir/ritonavir) when compared with little or
no change in the nonswitching arm of the NICE study strongly suggests
that participants may have been quite truthful in their responses. These
results may also apply to other twice-daily drug regimens (see below).
Of course, the significance will be underscored when viral load and
CD4 cell counts are reported after longer follow-up.
Several other studies at Durban indicated easier and improved adherence
with twice-daily dosing of PI drugs, many of which included twice-daily
nelfinavir after participants were switched from three-times-daily dosing.
One study found an equivalent level of adherence when comparing twice-daily
nelfinavir in combination therapy with once-daily efavirenz combination
DeJesus, E. and others. A randomized, controlled, open-label
study comparing the adherence and convenience of continuing indinavir
Q8H vs. switching to Norvir/indinavir 400 mg/400 mg BID (The NICE Study).
Abstract and oral presentation WeOrB482.
Dhingra, R. and others. Twice daily nelfinavir results
in greater durability and higher CD4 counts than TID dosing. Abstract
Hugen, P. and others. Compliance to HIV protease inhibitors
is more accurately measured by combining various methods, including
MEMS (electronic monitoring) and therapeutic drug monitoring [measuring
drug levels in blood]. Abstract ThPeB5029.
Morris, A.B. and others. The efficacy and durability
of BID nelfinavir in two clinics. Abstract WePeB4153.
Novak, R. and others. Effect of change from TID to BID
nelfinavir on viral load, CD4 count and adherence. Abstract WeOrB483.
A meta-analysis of 23 studies with HAART in treatment-naive (not previously
treated) persons was presented by John A. Bartlett, MD, of Duke University
Medical Center in Durham, NC. Dr. Bartlett showed that the total number
of daily pills is significantly inversely associated with HIV viral
load undetectability after 24 or 48 weeks. This means that a lower number
of daily pills is associated with a higher likelihood of achieving an
undetectable viral load. It also means that a higher number of daily
pills or capsules is associated with a lower chance of achieving viral
load undetectability. Dr. Bartlett had presented a similar meta-analysis
at this past Februarys 7th Conference on Retroviruses
and Opportunistic Infections (CROI). The study suggests that adherence
might be easier with a lower number of daily pills or capsules.
Bartlett, J.A. Correlation between antiretroviral pill
burden and durability of virologic response -- a systematic overview.
Abstract and poster presentation ThPeB4998.
Mitochondria, and Anti-HIV Drugs
Researchers from Perth, Australia, presented an interesting late-breaker
poster that provided some evidence to link lipoatrophy (fat loss under
the skin) with anti-HIV drug therapy and changes in the mitochondria
(energy producers) of cells. Skin biopsies from the hip or "buffalo
hump" area of HIV positive persons taking nucleoside reverse transcriptase
inhibitors (NRTIs) with or without PIs have abnormal appearances of
fat cells (adipocytes). These cells under the microscope or electron
microscope showed "abnormal adipocyte ultrastructure with mitochondrial
abnormalities, cytoplasmic [outside the nucleus] lipid [fat] accumulation,
and loss of adipocyte volume." In addition, there was associated
fat cell loss and lipogranuloma formation. Those who were taking both
NRTIs and a PI drug had more severe changes than those taking only NRTI
drugs. Also, S. Mallal, MD, from Royal Perth Hospital in Australia found that
these changes were seen in regions of fat loss (lipoatrophy) and accumulation
("buffalo hump"). (Note, however, that fat loss under the
skin can still be present when there is deeper fat accumulation, as
has been shown in the abdominal area.) HIV positive subjects without
any anti-HIV treatment had no abnormalities on electron microscopy,
but occasional lipogranulomata were seen on regular microscopy. Mitochondrial
toxicity has been proposed as a common mechanism of side effects from
certain drugs in the NRTI class. This is the first visual evidence of
possible anti-HIV drug toxicity associated with so-called lipodystrophy
(body fat changes).
Mallal, S. and others. Light and electron microscopy
findings in subcutaneous fat in antiretroviral treated and naive HIV-infected
patients. Abstract and late-breaker poster presentation LbPeB7054.
Predisposition to Lipodystrophy
In a late-breaker poster presentation, Dr. A. Alfirevic and colleagues
from the University of Liverpool in the UK found evidence for a genetic
predisposition to lipodystrophy. A specific gene variation (i.e., 238
polymorphism genotype) in the "promoter" region of tumor necrosis
alpha (TNF-alpha) was statistically associated with lipodystrophy in
HIV positive persons taking anti-HIV therapy. Dr. Alfirevic concluded
that the gene variation represents a susceptibility factor for developing
HIV-related lipodystrophy. These results need to be confirmed in a larger
Alfirevic, A. and others. Tumor necrosis factor-alpha
(TNF-alpha) promoter region gene polymorphism in patients with HIV-1
associated lipodystrophy. Abstract and late-breaker poster presentation
Two-Dose Nevirapine (Viramune) around Newborn Delivery Still Shows Significant Benefits at 12 Months
Attendees were pleased to hear additional follow-up of the landmark
HIVNET 012 study that had used only two doses of nevirapine to help
prevent HIV transmission from mother to newborn. Among the 311 mother-infant
pairs who received nevirapine (one dose for mother at onset of labor
and one dose for the infant within three days after birth), the HIV
transmission rate to those infants was 16%. Among the 308 mother-infant
pairs who received AZT (Retrovir) during labor and for the infants
first week of life, the transmission rate to those newborns was 24%. The difference between the two groups was statistically significant.
Among those mother-infant pairs who completed 12 months of the study,
95% of the infants were breast-fed. Among the 65% of mother-infant pairs
who completed 18 months, there were no additional infants who became
HIV positive in the nevirapine arm, while an additional four subjects
in the AZT arm became infected. The presenting author was M. Owor, MD,
from Mulago Hospital in Kampala, Uganda. However, attendees were disappointed
by the results of the PETRA trial (AZT plus 3TC) to prevent mother-to-child
transmission (see below).
Immediately prior to the Durban conference, Boehringer Ingelheim (BI)
Pharmaceuticals announced that the company will offer free nevirapine
for five years to resource-poor countries to help prevent HIV transmission
from mother to newborn. In a press release, BI said, "The initiative
is part of [the companys] commitment to the collaborative effort with
five companies (BI, Bristol-Myers Squibb, Hoffmann-La Roche, Glaxo Wellcome,
and Merck & Co.), United Nations Agencies (World Health Organization
[WHO], World Bank, UNICEF, UNFPA, and UNAIDS), and committed governments
to explore practical ways of working together to make HIV/AIDS care
available and affordable to a significantly greater number of people
in developing countries." This donation by BI is rather generous.
Countries with the greatest need for the medication usually do not have
the infrastructure to allow for appropriate HIV-related education, counseling,
blood testing, drug distribution, and follow-up of HIV positive women,
their infants, and sexual partners.
Boehringer Ingelheim press release. Boehringer Ingelheim
offers Viramune (nevirapine) free of charge to developing countries
for the prevention of HIV-1 mother-to-child transmission. July 7, 2000.
Owor, M. and others. The one year safety and efficacy
data of the HIVNET 012 trial. Abstract and late-breaker oral presentation
AZT plus 3TC Ineffective at 18 Months
One of the more disappointing studies presented in Durban was the 18-month
follow-up of the PETRA trial. Previously, the PETRA trial showed that
short-course AZT plus 3TC was able to reduce HIV transmission by 52%
to newborns at age six weeks. The dosing started at week 36 of pregnancy,
then continued during delivery and for one week after delivery for mother
and infant. Unfortunately, those benefits essentially are lost by the
time the infant reaches 18 months and is breast-feed without any continuous
anti-HIV therapy taken by infant or mother. Continuing to drink breast
milk infected with HIV outweighs the six-week benefits of short-course
AZT plus 3TC. The results were not necessarily unexpected given what
is known about HIV transmission via breast-feeding.
The double-blinded (i.e., medications were not disclosed to treating
physicians or study subjects), randomized, and placebo-controlled PETRA
study enrolled a total of 1,457 mothers and 1,501 infants from Uganda,
Tanzania, and South Africa (Durban and Johannesburg). The trial was
sponsored by UNAIDS (United Nations Programme on AIDS), with researchers
from the Netherlands and the three African countries. One-third of the
infants were delivered by cesarean ("C") section and 71% were
Six-week results were as follows. HIV infection or death occurred in
9% of the treatment arm and 21% of the placebo arm. (Shorter durations
or dosing combinations led to intermediate rates of HIV infection or
death.) The decreased relative risk was 0.48 for the treatment arm,
when compared with placebo; the results were statistically significant.
After 18 months, however, the difference was no longer statistically
different. The rate of HIV infection or death in the treatment arm was
21%, compared with 27% in the placebo arm. The relative risk in the
treatment arm was 0.78, i.e., not statistically significant. The results
show that AZT/3TC treatment around the time of infant delivery decreases
HIV infection rate or death at 6 weeks of age, but not at 18 months,
in a population in which a majority of women breast-feed. Additional
analyses may show benefits for those who did not breast-feed. The results
were presented by Glenda Gray, MD, from Baragwanath Hospital in Johannesburg
during a late-breaker session. Note that these results are different
from short-course nevirapine to prevent HIV transmission to newborns
Potential solutions will be to find a way to make breast-feeding safer
or to allow the substitution of safe, nutritious alternatives. Both
will prove challenging in many of the countries where the infrastructure
for sanitary food preparation and clean water is a problem.
Gray, G. and others. The PETRA study: early and late
efficacy of three short ZDV/3TC combination regimens to prevent mother-to-child
transmission of HIV-1. Abstract and late-breaker oral presentation LbOr5.
Nonoxynol-9 (N-9) Increases HIV Transmission
As a result of a study of female sex workers from Africa and Thailand,
UNAIDS has recommended that women at risk for HIV infection not use
N-9 products in the vagina. N-9 is a common spermicide (sperm-killing
agent) used in the vagina to help prevent pregnancy. It also has some
microcidal effects (i.e., it kills certain bacteria and/or viruses),
including HIV and other sexually transmitted infections, in laboratory
tests. In the U.S. and China, N-9 is available under the trade name
"Advantage S." The results of the triple-blind, randomized,
multicenter study of N-9 were discussed by Dr. Joseph Perriens and reviewed
by Dr. Isabelle de Zoysa during a plenary session in Durban.
The study enrolled 990 HIV negative women from Thailand, South Africa,
and Côte dIvoire (Africa). They were given HIV counseling, condom
promotion information, free condoms, and free treatment of sexually
transmitted diseases (STDs). The women were randomized to receive N-9
gel or the same gel vehicle without N-9 (a placebo) used intravaginally
before heterosexual vaginal intercourse.
The rate of new HIV infections per 100 "person-years"* was
10.2 in the placebo arm and 15.5 in the N-9 arm. During the observation
period, 41 women in the placebo arm and 59 in the N-9 arm became HIV
positive. However, the two study arms had a lower incidence (rate) of
new HIV infections than did control women who were not in the study.
Interestingly, the N-9 arm had higher rates of both gonorrhea
and chlamydiae cervical infections, but the differences were not statistically
significant. The trial was sponsored by UNAIDS.
In previous studies, N-9 has been shown to increase vaginal inflammation
(swelling with redness due to increased blood flow with increased white
blood immune cells). Sometimes, the top layer of cells was eroded or
no longer present (due to inflammation) which would mean an absence
or decrease of the normal protective barrier to infection.
A prior study (known as the VCF trial) published by Dr. Roddy and colleagues
found similar results in 1998. As a result of these studies, "UNAIDS
believes that women at high risk of HIV infection should not use N-9
[products], given that the bulk of the data now suggests that it is
either ineffective or harmful as an anti-HIV agent [in heterosexual
vaginal transmission]." Meanwhile, at least 13 other vaginal microbicides
are in the research pipeline as possible female-controlled products
to help decrease HIV transmission through the vagina. Some examples
are alkyl sulfates, Buffergel, and others.
* A person-year is the number of persons multiplied by the years (or
fractions of years) of follow-up, to allow for fair or equal comparisons.
For example, one person followed for two years equals two person-years,
as is two people followed for one year or four people followed for one-half
de Zoysa, I. Track C plenary rapporteur session.
UNAIDS press release. UNAIDS calls for continued commitment
to microbicides. July 12, 2000.
Viral Loads Are Similar among Women and Men
Previously, there had been conflicting information about HIV viral
load differences when comparing women with men. Now, a meta-analysis
of six clinical trials confirms that women have no significant differences
in HIV RNA viral load when compared with men. Women with advanced HIV
infection had insignificantly lower viral loads than men with the same
CD4 cell counts. Conversely, at higher CD4 cell counts, women had insignificantly
higher viral loads than men with similar CD4 cell counts. The lead author
was Dr. Starley B. Shade from the Terry Beirn Community Programs for
Clinical Research on AIDS (CPCRA) and the University of California,
Shade, S.B. and others. Gender differences in viral
load: results from six clinical trials. Abstract and poster presentation
APRICOT Study Begins
A randomized, placebo-controlled trial of 741 persons with HIV/hepatitis
C virus (HCV) coinfection began this past summer. The purpose of the
study is to compare the potential benefits of adding anti-HCV combination
therapy in coinfected persons who are already taking HAART for HIV.
Subjects in the three study arms taking HAART will add peginterferon
alfa-2a (Pegasys) with or without ribavirin (Rebetol), or interferon
alfa-2a (Roferon-A) with ribavirin. The pegylated form of interferon
alfa is an experimental, long-acting version that is dosed once weekly
by injection. The dose of ribavirin will be 800 mg, which has been used
more commonly in HIV-HCV-coinfected persons. The standard dose is 1,000
mg (in persons 165 lbs or less) or 1,200 mg (in people greater than
165 lbs) in HCV positive persons without HIV infection. Therapy will
be taken for 48 weeks with additional follow-up 24 weeks later to measure
the sustained virologic response.
Due to in vitro antagonism (canceling effects), there have been
some concerns about adding ribavirin (a nucleoside analog) to HAART
regimens including either d4T or AZT. Francesca J. Torriani, MD, of
the University of California, San Diego, described the new study during
a satellite symposium called "Fabric of the Future." Dr. Torrianis
presentation was entitled, "New Developments in the Management
of HIV Co-Infections: HCV and CMV."
Torriani, F.J. New developments in the management of
HIV co-infections: HCV and CMV. Satellite symposium.
HCV Coinfection Increases HIV DiseaseProgression after HAART
While HIV has been shown to increase HCV disease progression, the effects
of HCV upon HIV disease are somewhat less clear. Now, results of a large
cohort study from Switzerland show a significant progression of HIV
disease after HAART was started in coinfected subjects. Anti-HIV therapy
was started in 1,157 subjects (34% women), who were compared with 1,954
persons with HIV monoinfection (without HCV) who started treatment.
The large Swiss Cohort was followed for more than four years. Results
after three years of treatment showed that the proportion who were alive
and without clinical progression of HIV disease was 80% among HIV-HCV
coinfected persons who continued injecting drugs, 85% among HIV-HCV
coinfected persons who stopped injecting drugs, and 90% among those
who were only infected with HIV and not injecting drugs. These differences were highly statistically significant. HIV-HCV coinfected
participants had a 1.7 "relative hazard" of HIV/AIDS progression
or death when compared with persons infected only with HIV in a "regression
(statistical) analysis" that included other potential cofactors,
including HCV viral load. The researchers found that coinfected persons
had a reduced ability to increase CD4 cell counts after achieving HIV
RNA viral undetectability, when compared with HIV monoinfected subjects.
The lead author was G. Greub, MD, of the University Hospital in Lausanne,
Greub, G. and others. Negative impact of HCV infection
on HIV progression, survival, and immune restoration in the Swiss HIV
cohort studies. Abstract and poster presentation MoPeB2139.
Acute Infection with Hepatitis B Virus (HBV) Is Six Times More Frequent Among Those with HIV Infection
The Centers for Disease Control and Prevention (CDC) has reported that
those with HIV infection have a significantly higher rate of acute infection
with HBV when compared with the general population. In people with HIV
infection (and much less commonly among those without HIV infection),
HBV infection can be lethal. HBV is transmitted by the same mechanisms
More than 11,000 HIV positive persons from 11 U.S. cities in the Adult
and Adolescent Spectrum of HIV Disease Project (ASD) were followed between
1997 and 1998. Only 11% of enrollees with no history of acute or chronic
HBV had one or more doses of HBV vaccine. Current guidelines by the
U.S. Department of Health and Human Services/Infectious Disease Society
of America (USPHS/IDSA) recommend the HBV vaccine series for all HIV
positive persons with a negative test for HBV core antibody. Among participants,
74% had taken 3TC as a part of anti-HIV therapy. (3TC also has anti-HBV
activity and is one of two drugs that is FDA-approved to treat chronic
HBV infection.) There was a 54% decreased risk of acute HBV infection
among persons without previous HBV infection who had taken 3TC.
Kellerman, S.E. and others. Incidence of acute hepatitis
B in HIV infected individuals and the protective effect of hepatitis
B vaccination and lamivudine. Abstract and poster presentation MoPpA1082.
Harvey S. Bartnof, MD, has been a member of the Scientific Advisory
Committee of the San Francisco AIDS Foundation since 1987.
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