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Past Issues
Volume 14, number 9/10
September/October 2000
Contents
The Durban Conference
A South African looks at the issues facing his country
Eliminating Mother-to-Child Transmission
What's really possible now?
Body Fat Changes
New research, many questions
Reading Durban
Our guest editor reads the conference proceedings
What Happened in Durban?
A South African Perspective
By Nathan Geffen
Durban, South Africa's port city on the Indian Ocean, sits at the
epicenter of one of the world's largest and most complex HIV epidemics.
Like South Africa's other major cities, it encompasses a mix of
the first and the third world. Interspersed among fine hotels, the
huge and modern International Conference Center and a wonderful
array of gardens, restaurants and shopping malls, one finds hundreds
of people living on the street, many of them sleeping under plastic
covers on the Durban Beach front. Just a short drive from the city
center, one comes across the densely populated townships, their
underlying poverty deceptively disguised by the omnipresent sub-tropical
vegetation of Kwazulu-Natal, notorious for being, until recently,
the venue of some of South Africa's most violent political clashes.
The 13th International AIDS Conference, which took place in Durban
in July, dominated the main pages of the country's newspapers and
the prime slots on TV, an indication that South Africans are becoming
increasingly aware of the damage this disease, and the lack of an
appropriate response to it, is causing to the social and economic
fabric of this society.
The enormous cost of the entrance tickets to the conference prevented
many South Africans from attending. A ticket cost approximately
$700, an amount exceeding the monthly salaries of even many middle-class
South Africans. There were three groups of South Africans who managed
to get tickets: (1) those who knew the right people, (2) the incredibly
wealthy and (3) those with access to a high-quality color photocopying
machine, useful for making fraudulent tickets. The inappropriate
opulence of the event was evident at the opening ceremony, which
was punctuated with dance and song routines more suitable for the
gala opening of the Olympics. It was concluded with a fireworks
display. It is perhaps not entirely ironic that those denied access
to treatment were also denied access to the conference and the fireworks
show.
Despite the expense and inappropriate celebratory atmosphere of
the opening ceremony, the conference had many memorable events,
including speeches by Judge Edwin Cameron, a judge on the South
African High Court, and Winnie Mandela, ex-wife of the country's
first democratic president and one of the most popular political
figures in the country, who both criticized the pharmaceutical industry
for its role in worsening the HIV epidemic. Both urged the South
African government to lead the fight to bring affordable HIV medication
to South Africa. A speech by Nelson Mandela later called for a mother-to-child-transmission
prevention program.
Other memorable events included a free satellite conference, organized
by Doctors without Borders and the Treatment Action Campaign, on
access to treatment. The satellite meeting was attended by over
a thousand people from around the world, as well as many sectors
of South African society. Other important events included an overwhelming
consensus among diverse scientists, academics, governments and laypeople
that affirmed the causal link between HIV and AIDS, and clear findings
from both Uganda and South Africa on the efficacy of both AZT and
nevirapine (NVP) as prevention in mother-to-child transmission of
HIV.
However, the Global March for Treatment Access, organized by the
Treatment Action Campaign and the Health-GAP Coalition, must be
considered the highlight of the conference. Thousands of people,
most of them economically marginalized, working-class South Africans,
marched through the streets of Durban, demanding access to affordable
and decent health care. It was a remarkable demonstration of power
by ordinary South Africans and represented the mobilization of civil
society in a maturing democracy. The international contingent at
the march, which comprised many activists from developing countries,
emphasized the global nature of HIV and the need to form worldwide
alliances to overcome it.
The march culminated in the handing over a memorandum to representatives
of UNAIDS, the South African government and the organizers of the
International AIDS Conference. Conspicuous by their absence were
Harvey Bale, chairperson of the International Federation of Pharmaceutical
Manufacturers Associations, and Sandra Thurman, director of the
United States Office of National AIDS Policy, who were both invited
to receive the memorandum. The world's media reported extensively
on the march and its aims, which contributed to ensuring that access
to treatment became one of the primary focuses of discussion during
the remainder of the conference.
The 1999 annual survey of women attending public antenatal clinics
indicated a sero-prevalence rate of 22.8 percent. Extrapolating
from this survey, the government estimates that 4.2 million South
Africans have HIV. The seriousness of the HIV epidemic in South
Africa and the potential catastrophe resulting from it cannot be
doubted; the Durban marchers deserve to be answered. The problems
affecting treatment access in South Africa need to be analyzed and
resolved. There are four major obstacles to treatment access: (1)
the high price of medication due to pharmaceutical company profiteering,
(2) government intransigence, (3) health-care infrastructure issues
and (4) lack of knowledge concerning HIV at a grassroots level.
High Prices of Medication Because of Profiteering
The price of medication is the biggest obstacle to treatment access.
This writer recently calculated that the cheapest amount for which
a South African could legally obtain triple-drug antiretroviral
therapy is over $285 per month. More than 50% of South African households
have an income of less than $200 per month. Even a middle-class
South African household would struggle to cover the price of treatment
of one person. Taking triple-drug therapy is inconceivable to all
but a small minority of people, who are either very wealthy or on
a drug trial.
The cost of many opportunistic infection drugs are also exorbitant.
Systemic thrush and cryptococcal meningitis are two common opportunistic
infections associated with HIV. Both are often fatal if left untreated.
Pfizer sells fluconazole to the South African government for approximately
$4 per 200 mg pill. Usually two pills are needed a day. When one
considers that cryptococcal meningitis patients need to take fluconazole
for the rest of their lives, the inaccessibility of the drug becomes
apparent.
Pharmaceutical companies, like Pfizer, are profiteering from life-saving
medications. High-quality generic fluconazole is available from
Thailand (and other countries) at less than $0.29 per 200 mg pill,
but Pfizer is using its patent on the drug in South Africa to monopolize
the market and prevent generic competition. Almost every nucleoside
and non-nucleoside antiretroviral drug is also available cheaper
from generic manufacturers, though the price differential on fluconazole
is a particularly staggering example. Through long-running, ongoing
legal action by the pharmaceutical industry and bullying tactics
by the US and EU governments, the South African government has been
intimidated out of its attempts to use legislation which would allow
it to grant compulsory licenses for the manufacture or importation
of these essential medications. Therefore, these cheaper drugs are
unavailable to the vast majority of the South African public.
The main thrust of TAC's campaign has been to highlight profiteering
via patent abuse of pharmaceutical companies. Earlier this year,
a campaign was launched to get Pfizer to drop the price of fluconazole
to less than $0.60 per tablet or to grant a voluntary license to
import the drug from a generic manufacturer. Pfizer responded by
offering to donate fluconazole for free to patients with cryptococcal
meningitis (systemic thrush is excluded), but despite months of
negotiations with the government, the offer has still not gone into
effect.
It is against this background that TAC has decided to take legal
action against Pfizer on the grounds of abuse of patent and to begin
a defiance campaign by importing high-quality generic fluconazole
into South Africa, which TAC is distributing free to doctors and
patients. This is being done on humanitarian grounds in order to
save human lives. Many TAC volunteers are in urgent need of fluconazole
and many doctors have indicated that they are in dire need of the
drug for their patients.
Government Intransigence
The South African government has implemented an excellent legal
framework for dealing with HIV/AIDS. It has also invested substantially
in prevention campaigns and condom distribution. However, in other
respects their response has been less than adequate. Besides the
well-publicized flirtations of President Mbeki with AIDS denialists
(which undermines the prevention campaign), the government is doing
its utmost to avoid implementing a mother-to-child-transmission
prevention (MTCTP) program. An mtctp program using nevirapine (NVP)
or AZT would prevent approximately 14,000 babies a year from contracting
HIV. Despite the success of a pilot program in Khayelitsha (Cape
Town), the recently completed SAINT trials (which tested the efficacy
of NVP) and the results of trials that have taken place in Botswana,
Kenya and Uganda, the government continues to use red herrings,
such as the resistance profile of NVP and transmission of the virus
through breast-feeding, to avoid fulfilling its responsibilities.
A recent study at the University of Cape Town demonstrated that
the government would save money by implementing an mtctp program.
The cost of treating HIV children far exceeds the fraction (less
than 1%) of the health budget it would require to prevent them from
contracting the virus.
TAC is mobilizing a campaign, comprising protests, pamphleteering,
educational workshops and legal action to ensure that a countrywide
MTCTP program is implemented. The legal case for compelling the
government to implement MTCTP is based on a number of constitutional
rights upon which the government's current stance is infringing:
(1) the right to healthcare, (2) the best interests of the child,
(3) the right to equality and dignity and (4) the right of a woman
to make reproductive choices.
Health-Care Infrastructure
There is currently a two-tier health-care system in South Africa
— one private and one public. Private healthcare in South Africa
is generally excellent and very profitable, but the cost ensures
that a minority of people has access to it. Service in the public
health-care system is uneven with many centers of excellence and
many appalling wards and institutions. Many rural areas are under-serviced,
and often lack access to clean water.
But it is not only the rural areas. TAC volunteers recently visited
a volunteer sick with cryptococcal meningitis in a ward in King
Edward Hospital in Durban, which has a reputation of being one of
the country's finest hospitals. They were appalled to find the walls
of an overcrowded ward smeared in vomit and the floors damp with
urine, a situation that was remedied after a complaint was laid.
This is the result of a system where hospitals and clinics are understaffed.
Health-care workers are underpaid and have become demoralized by
visibly increasing death rates often due to a lack of access to
essential medication.
The situation is definitely not hopeless. There has been some investment
into the primary health-care infrastructure by the post-apartheid
government. Tuberculosis treatment is free, widely available and
implemented using the Directly Observed Treatment Short Course program.
South Africa has been recognized by the World Health Organization
as one of the countries making progress in tuberculosis control.
Interestingly, apologists for the pharmaceutical industry often
argue that infrastructure is the biggest obstacle to access in South
Africa and that the conditions do not exist for ensuring adherence
to anti-retroviral drug regimens. However, they fail to point out
that adherence is a problem in the US and the EU as well, and that
the same adherence argument could be applied to TB treatment in
South Africa. Yet, no one would suggest that triple-drug therapy
should be stopped in the developed world or that TB treatment should
not be given in South Africa. There is no empirical evidence that
socioeconomic status is correlated with adherence.
Addressing infrastructure problems is difficult and will require
substantial investment by the government, as well as a greater contribution
by private health-care users to the public health-care system. But,
lowering drug prices will provide much needed funds. Campaigning
for conditional third-world debt relief linked to the development
of health-care infrastructure and other essential social services
might be a strategy worth considering in this regard. The South
African government is considering making a $200 million loan from
the World Bank to improve the health-care infrastructure. This is
a fraction of the $6.8 billion that South Africa spends on servicing
its debt, most of this incurred by the apartheid government.
Lack of Knowledge/Social Stigma
Extreme examples of the social consequences of the stigma against
HIV in South Africa include the murders of Mpho Motloung and Gugu
Dlamini. Ms. Motloung was murdered by her husband when both went
for their HIV test results. Ms. Dlamini, an openly HIV-positive
advocate, was stoned to death by a mob. Fear and ignorance are the
catalysts for such brutal behavior. This situation is exacerbated
by the continuous message coming through in both the media and the
government prevention campaign that HIV is a death sentence, a view
strongly opposed by TAC. Not only has this message resulted in much
misery (and abuse of women as in the Motloung and Dlamini cases),
but it also discourages people from having HIV tests or disclosing
their HIV status. It also undermines prevention because people with
HIV are discriminated against and believe their situation is hopeless.
TAC is combating this stigma in a number of ways. At the Durban
March, the marchers wore t-shirts with the words "HIV Positive."
The HIV Positive t-shirt was first used to protest the death of
Gugu Dlamini and has since become a symbol of openness and activism.
Many TAC volunteers are open about their HIV status and are spreading
the message that HIV does not imply a death sentence.
Treatment Knowledge
Many South Africans do not realize that HIV can be treated or that
their health can be improved through lifestyle changes. TAC holds
regular treatment workshops in townships. These workshops involve
educating people about how to live healthier with the disease and
that there are treatments that can help them live much longer, if
the prices of these treatments could be brought down. However, the
organization does not have the money to implement this on a large
enough scale. Government, civil society and the private sector should
be investing more resources into treatment education.
TAC has received many requests by people living in the United States
who wish to know how they can help. There are many ways. Organizations
like Health-GAP and the Consumer Project on Technology have worked
on campaigns and issues with TAC. The Treatment Action Group has
assisted us by providing us with technical information on treatment.
The European and US media often points out the negative role of
the South African government in the epidemic, justifiably so, but
very little is said about the roles of the European and US governments
as well as the pharmaceutical industry. Only citizens of the EU
and the US can change this inequity in coverage. It is worth organizing
campaigns to highlight the negative role of the pharmaceutical industry
in the epidemic. Too few people in the world's developed countries
are aware of the misery caused by some of their institutions and
corporations. Let us work together to change this and to overcome
the health gap.
Success in Preventing
Mother-to-Child Transmission Not a Reality for All
By Jill Cadman and Donna Kaminski
One of the most important themes at the International AIDS Conference
in Durban was the prevention of mother-to-child transmission of
HIV (MTCT). This was very appropriate given that one in four South
African women in their peak child-bearing years — between the
ages of 20 and 29 — are HIV-positive.1 In addition,
rates of HIV infection in prenatal clinics in sub-Saharan Africa
can run as high as 43%.2 While progress to reduce the
rates of MTCT continues to move steadily forward, the conference
highlighted the global disparities between developed and developing
countries in implementing such interventions.
Rates of transmission in developed countries have dramatically
decreased due to widespread efforts to provide pregnant women with
access to HIV testing and counseling and information on the benefits
of antiretroviral therapy and the risks of breast feeding. In contrast,
many developing countries are still struggling to implement small
pilot programs and studies that reach only a tiny fraction of HIV-positive
pregnant women. Many women in developing countries still have little
access to education, testing and counseling and no option but to
breast feed, another factor that leads to transmission. While in
the US, the emphasis of the Public Health Service Guidelines for
the Use of Antiretroviral Agents in Pregnant Women is on the best
treatment for the woman's health; in Africa, the focus is solely
on preventing MTCT. The only option most African women have is to
try and obtain a small amount of antiretroviral medication during
pregnancy. While this may interrupt transmission, it does nothing
to help the mother combat HIV and there is generally no additional
antiretroviral medication available to her after the birth of her
baby.
Spreading the Good News
After the results of the pivotal ACTG 076 trial were announced
in the mid-1990s, the standard of care for treating pregnant women
dramatically changed to incorporate the use of AZT starting between
the 14th and 34th week of pregnancy and continuing intravenously
during labor and in the newborn for six weeks after delivery. Results
of ACTG 076 demonstrated that the AZT regimen could reduce the risk
of MTCT by two-thirds. As reported in Durban, widespread implementation
of this regimen and other, more potent combination regimens has
led to impressive reductions in levels of transmission in industrialized
nations.
While the largest proportion of information available is still
on the prenatal use of AZT monotherapy, and the longest follow-
up has been in AZT-exposed infants, more and more women are using
combination therapy during pregnancy. In addition, women are increasingly
on treatment prior to conception and are continuing throughout the
pregnancy with no interruption during the first trimester. This
has raised concerns about possible toxicity of the other antiviral
agents. Several studies reported in Durban from the US, Puerto Rico
and Europe examined the safety and efficacy of combination therapy.
Carmen Zorilla, MD, from the University of Puerto Rico School of
Medicine presented a chart review of 77 women between 1997 and 1999.
By 1999, 86% of women were on protease inhibitor-containing regimens.
One third of women were on therapy prior to the time of conception
and did not discontinue treatment at any time during the pregnancy.
The transmission rate was zero in all women and perinatal outcome
was good. Most common adverse events in infants were anemia (18%)
and candidiasis (13%). The rate of elective cesarean sections increased
over time to a peak of 100% in 1998 and 89% in 1999. While C-sections
are discussed with each patient, Dr. Zorilla stated, "It is an offer...It
is becoming more and more accepted that a C-section is not as useful
in women with undetectable viral loads on HAART and vaginal delivery
is a real option." The American College of Obstetricians and Gynecologists
advised in an official statement in May 2000 that data are insufficient
to demonstrate a benefit of elective C-sections for pregnant women
with viral loads less than 1,000 copies. The rate of preterm deliveries
(<37 weeks) was 20%. However, Dr. Zorilla pointed out that 95% of
infants were delivered at 35 weeks or more. While this is considered
preterm, she stated that at 35 weeks the infants' chances of survival
are as good as at full term (40 weeks), as they usually do not need
an incubator, have acceptable birth weight and few morbidity risks.
Some of the women who delivered prematurely had risk factors for
preterm birth, such as intravenous drug use. (Abstract WePpB1303.)
Dr. Thorne from the Institute of Child Health in London presented
data on 2,633 women enrolled and prospectively followed in the European
Collaborative Study between 1985 and 1999. Whereas in 1994 all women
received AZT monotherapy, by 1998/9 24% received double therapy
and 41% triple or quadruple therapy. A growing number of women became
pregnant while on therapy (12% in 1998/9). These women had been
on antiretrovirals for an average of 25 months before pregnancy.
Antiretroviral exposure in utero was not associated with prevalence
or pattern of congenital abnormalities but was associated with moderate
to severe anemia in the infant. The overall rate of MTCT was 5.4%
in 1998/9 compared with 16% before 1994. Dr. Thorne is currently
working on an updated analysis including infants delivered up to
June 2000, which demonstrates that the rate of MTCT since 1998 has
dropped even further to 2.1%. (Abstract MoOrC240.) Finally, in a
late breaker presentation from the Institute of Human Virology,
results were reported from WITS (Women and Infants Transmission
Study) on 1,482 women prospectively followed from 1990 to 1999.
MTCT rates markedly declined based on potency of the antiretroviral
combination: 20.7% for no treatment; 7.7% for AZT monotherapy following
the 076 protocol; 3.9% for combination therapy without protease
inhibitors and 1.1% for HAART. Transmission rates increased with
increasing viral loads at delivery: 0.9% for under 400 copies; 6.4%
for 400-3,000 copies; 11.3% for 3,000 - 40,000 copies; 21.1% for
40,000 - 100,000 copies and 30.1% for over 100,000 copies. There
were two women whose viral loads were less than 400 at delivery
who transmitted: one received HAART for one month before delivery
but was taking illicit drugs during pregnancy; the other received
combination therapy but the duration of membrane rupture (time since
breaking of the bag of waters) was greater than 24 hours. (According
to previously reported WITS data, the risk of MTCT nearly doubles
when the membranes rupture more than four hours prior to delivery.3)
(Abstract LbOr4.)
All in all, good progress was reported toward maximal reduction
of MTCT. Some conference presenters even referred to the potential
"elimination" of pediatric HIV in the developed world. This was
largely based on the widespread acceptance of HIV testing in pregnant
women and the use of HAART. One CDC study in close to 6,500 perinatallyHIV-exposed
children born in 1994 to 1998, documented that the percentage of
mothers tested for HIV before birth had increased from 80% to 96%
(Abstract MoOrC239). Once a woman knows her HIV status, she can
make an informed decision about treatment options for herself and
her baby. This was reflected in the increasing use of HAART during
pregnancy. The use of more potent regimens does not appear to be
associated with increased adverse events in mother or child and
does appear to be associated with reduced transmission (independent
of viral load at delivery). The theme at the conference was how
these interventions could be modified for the developing world for
women who do not have access to the wide range of drugs available
in industrialized nations.
Encouraging Results from MTCT Studies in the Developing World
Results from numerous international studies showed promise in reducing
MTCT with simpler and less-expensive regimens than those used in
developed countries. Thailand has been especially progressive in
designing and implementing prevention programs to address MTCT.
At the conference, data were reported on the Perinatal HIV Prevention
Trial, a large-scale placebo-controlled trial comparing four treatment
regimens using different durations of AZT therapy: (1) long-long
arm: AZT starting at 28 weeks for mother, oral AZT during labor
and for six weeks in the infant; (2) long-short arm: AZT starting
at 28 weeks for mother, oral AZT during labor and for 3 days in
the infant; (3) short-long arm: AZT starting at 35 weeks for mother,
oral AZT during labor and for 6 weeks in the infant; (4) short-short
arm: AZT starting at 35 weeks for mother, oral AZT during labor
and for 3 days in the infant.
After an interim analysis, the short-short regimen was found to
be significantly less effective than the long-long and was dropped.
When further analysis was undertaken to evaluate the other three
treatment arms in the 1,437 women enrolled, transmission rates across
the regimens were found to be comparable. MTCT was as follows: 6.5%
in the long-long arm, 4.7% in the long-short arm and 8.6% in the
short-long arm. However, while equivalence between the long-long
and long-short arms was established, equivalence with the short-long
arm was only border-line. Shortening the maternal treatment period
was associated with reduced overall efficacy and higher infection
rate at birth (5% for short maternal treatment, 1.8% for long treatment).
The authors conclude that both the long-short and long-long regimen
appear safe and effective and are simpler and cheaper than the original
076 protocol. While treatment of the infant for six weeks may not
add benefit when the mother receives longer prenatal treatment,
it may prevent some infections when mothers receive shorter treatment.
(Abstract LbOr3.)
While the shorter course Thai regimens cost significantly less
than 076, they are still too costly for many parts of the developing
world. In response to the need for even less expensive interventions,
HIVNET 012 was undertaken. This trial examined the safety and efficacy
of very short course AZT versus even shorter course nevirapine in
a breastfeeding study population in Uganda. The nevirapine regimen
consisted of single dose to the mother at the onset of labor and
a single dose to the infant within 72 hours of birth. The AZT regimen
consisted of an oral dose administered at the onset of labor and
continued through delivery and one week of AZT twice daily to the
infant.
Nevirapine has several important characteristics that make it a
good candidate for use in preventing MTCT. It is considerably more
potent than AZT and able to suppress HIV replication much more effectively
and quickly. It is rapidly absorbed when taken orally, entering
the bloodstream and beginning to work almost immediately. It has
been well established that nevirapine can cross the placental barrier.
It also has a long half-life (61 to 66 hours in pregnant women and
45 to 54 hours in babies), meaning that therapeutic levels of the
drug persist and continue to work days after the drug is taken.
Preliminary data from HIVNET 012 were released last year (see Treatment
Issues, Winter 1999/2000, pages 14-17). Final transmission rates
and safety data were presented in Durban for 619 women through infant
age 12 months. Results were not significantly different to the preliminary
analysis. Transmission rates at birth were essentially equivalent
in both arms: 8.1% for nevirapine versus 10.3% for AZT. However,
after 12 months in this breast feeding population, MTCT rates had
increased to 15.7% in the nevirapine arm versus 24.1% in the AZT
arm. Nevirapine showed a 39% reduction in MTCT compared to AZT.
In addition, the benefits of nevirapine occurred despite breast
feeding by the women in the study. The reason for this is unclear.
Both regimens appear to be well tolerated. According to the researchers
no adverse event was definitely or probably related to the study
drugs. (Abstract LBOr1.)
An eagerly anticipated report at the conference was from the South
African Intrapartum Nevirapine Trial (SAINT). This large study examining
short-course treatments in over 1,300 women was particularly relevant
because it was conducted in South Africa. The successful outcome
of the trial indicates that the positive results demonstrated in
HIVNET 012 and other international trials are reproducible in South
African women. SAINT randomized study participants to receive either
nevirapine or AZT/3TC. The SAINT nevirapine regimen was slightly
different to that used in HIVNET 012 in that the mother received
two doses instead of one. Not all women breast fed, 40% opted to
bottle feed.
The nevirapine arm consisted of one dose during labor and a second
dose 24 to 48 hours after delivery to the mother and a single dose
to the infant. The AZT/3TC arm consisted of AZT/3TC at onset of
labor and through delivery and then twice daily to the mother and
infant for one week. Rates of MTCT between the arms were comparable
at birth: 8.2% for nevirapine and 6.8% in the AZT/3TC arm. By week
eight, transmission had increased to 14% in the nevirapine arm and
10.8% in the AZT/3TC arm. This difference was not statistically
significant. Both regimens appeared relatively safe. There were
no serious treatment-related adverse events in either regimen in
infants or mothers. Neither liver problems nor significant skin
rash were documented in the mothers. Two children experienced skin
rashes, but these were not clinically significant. (Abstract TuOrB356.)
Finally, another interesting study from South Africa looked at
short courses of antiretroviral agents that have not been as widely
investigated as AZT, 3TC and nevirapine. Glenda Gray, MD, of the
Chris Hani Baragwanath Hospital in Soweto, presented results of
study A1455-094, which was sponsored by Bristol-Myers Squibb to
look at the safety and efficacy of its two drugs, ddI and d4T, in
comparison to an AZT monotherapy arm. The regimens consisted of
ddI versus d4T versus ddI/d4T versus AZT initiated in the mother
at 34 to 36 weeks gestation and continued through delivery and for
six weeks exclusively in the infants. This study is being conducted
in a non-breast feeding cohort, which, in conjunction with the fact
that the infants are receiving treatment for a full six weeks, may
account for the very favorable outcomes. In the preliminary data
analysis of about 200 women at six weeks, there was a significant
reduction in transmission to 3.6% in the overall study group. Rates
of MTCT were equivalent across all study arms. Maternal and infant
safety evaluations demonstrated no significant treatment-associated
toxicities. Dr. Gray stated that there was good transfer of the
drugs across the placenta. This is encouraging early data and shows
that other antiretroviral agents appear safe and effective and give
women additional options. However, estimated cost of the regimens
are $60 to $100 per mother/infant pair, which is higher than the
HIVNET 012 regimen. (Abstract TuOrB355.)
Access to Nevirapine for the Developing World
The cost of the HIVNET 012 nevirapine regimen is only about $4
US per mother/infant pair. This makes it "one of the few deliverable
and sustainable strategies for prevention of HIV transmission resource-poor
settings," according to the investigators of the study in a 1999
Lancet article.4 In addition, safety data from about
700 mother/infant pairs has shown no important adverse reaction
with single dose nevirapine, according to a more recent Lancet article.5
The National Institute of Allergy and Infectious Diseases (NIAID),
the sponsor of the HIVNET 012 study, issued a press release last
year stating that if the single-dose nevirapine regimen is "implemented
widely in developing countries, it potentially could prevent some
300,000 to 400,000 newborns per year from beginning life infected
with HIV."6
Immediately before the International AIDS Conference in July, Boehringer
Ingelheim, the manufacturer of nevirapine, announced that it would
make the drug available free of charge to developing countries for
a period of five years for the prevention of MTCT. While this lowers
the cost barrier for offering this intervention, other obstacles
still remain. Access to health care services is required: such basics
as voluntary counseling and testing are not available to all pregnant
women in developing countries. In addition, many women who are tested
refuse to return for their results. Presumably, the availability
of affordable and effective interventions to reduce the risk of
MTCT would be an incentive for more women to agree to counseling
and testing. A combination of counseling and testing, with the immediate
provision of nevirapine, could increase the number of women treated.
However, the South African government seems reluctant to commit
to making nevirapine more widely available. The South African Minister
of Health has stated, "Nevirapine currently should not be used outside
approved research environments,"and instead offered only to "expand
the research sites on nevirapine to all the provinces so that we
can improve our understanding of the operational challenges that
would attend any introduction of antiretrovirals to prevent MTCT
in the public health system." The South African group TAC is calling
for stronger measures from the government to make the drug more
widely available.
The Downside of Nevirapine Use
While the efficacy and low cost of short-course nevirapine has
generated much excitement throughout the global community, recent
data presented at the Durban conference unmasks a drawback associated
with its use as described in HIVNET 012: drug resistance. Two studies
demonstrated development of nevirapine-resistant mutations in the
virus of the mother and the infant after exposure to the single-dose
regimen.
J. Brooks Jackson, MD, from the Johns Hopkins Medical Institutes
in Baltimore, presented resistance data from HIVNET 012. Genotyping
was conducted on 30 treatment-naive study subjects who received
a single dose of nevirapine at the onset of labor. This revealed
that at six weeks postpartum, seven (23%) of the 30 women had developed
nevirapine mutations. The common K103N resistance mutation, which
confers cross-resistance to all non-nucleoside analogs (NNRTIs),
was found in all seven of the women. This raises the question of
whether nevirapine would be effective in preventing MTCT in a second
pregnancy. Data were presented demonstrating that the presence of
the nevirapine resistance mutations tended to decline in the mothers
over time (two-six months). Whether resistant virus would reemerge
quickly enough after nevirapine dosing in a second pregnancy to
impede efficacy is unclear. The investigators expressed the opinion
that the HIVNET 012 regimen could probably be used effectively in
subsequent pregnancies. The nevirapine-resistance mutations were
also detected in three of the seven infected infants. The clinical
significance of the mutations in the infants is as unclear, with
no effect on one-year mortality rates. (Abstract LbOr13).
John Sullivan, MD, from the University of Massachusetts Medical
School, presented a second study about nevirapine resistance. Dr.
Sullivan analyzed genotypes of NNRTI-naive women participating in
the US trial PACTG 316, which evaluated the efficacy of a single
dose of nevirapine versus placebo to the mother and infant to reduce
MTCT in women receiving open-label antiretroviral treatment. Genotyping
was conducted on 37 women for resistance mutations. The investigators
found that a nevirapine-resistance mutation was found in one woman
prior to administration of nevirapine, and three of the 37 women
developed nevirapine resistance post-nevirapine administration.
It is important to note that this study is still blinded so investigators
do not know if the women with the nevirapine mutations were being
dosed with the drug or placebo. (Abstract LbOr14.)
These findings are disappointing because they suggest that a single-dose
administration of nevirapine may set women and HIV-positive infants
at a future disadvantage to not only nevirapine but to the entire
class of NNRTIs prior to ever starting antiretroviral therapy. However,
in resource-poor settings where NNRTIs are not expected to be available
in the near future, the costs and operational advantages of the
nevirapine regimen may make it an attractive option. Both Drs. Jackson
and Sullivan stressed that the occurrence of the resistance mutations
should not be used as an excuse by governments to delay implementation
of short-course regimens to prevent MTCT in the developing world.
While single-dose nevirapine may still be advantageous in preventing
MTCT in developing countries, it is probably not a good option for
women in developed countries who are already on effective treatment.
The only case where the benefit might outweigh the risk of resistance
to US women would be for an HIV-positive woman whose status was
identified late in her pregnancy. In this scenario, according to
the Public Health Service (PHS) Guidelines, a women would be offered
four options, one of which is a single dose of nevirapine at the
onset of labor followed by a single dose for the newborn at age
48 hours. (The other three options consist of short-course AZT/3TC,
AZT monotherapy or AZT/nevirapine.) Women would be evaluated after
delivery to determine if antiretroviral treatment would be indicated
for their own health.
Lynne Mofenson, MD, of the National Institutes of Health, suggested
some theoretical ways that one might reduce the likelihood of the
development of resistance. "The hypothesis is that if one kept viral
replication very low in the mother during the period that nevirapine
drug levels decrease and become negligible (probably about one week
or so) than resistance shouldn't develop. Adding Combivir (AZT/3TC)
for one week to the mother (and then stopped) is one possible choice
because of ease of administration. Another choice would be the initiation
of HAART very soon after delivery. This should inhibit viral replication
and hence development of resistance as well, if not better, than
my hypothetical Combivir suggestion. HAART would continue in the
mother for therapeutic purposes. My suggestion of one week of Combivir
(in conjunction with single dose nevirapine) is more relevant to
developing countries where HAART is not available. In actuality
in the US, for most women, it would be recommended that the mother
initiate HAART postpartum and continue it for her own treatment."
About the "M" in MTCT and Breast feeding
The whole issue of short-course regimens that provide antiretroviral
medication to the mother only during pregnancy generated a great
deal of controversy at the Durban conference. The keynote speaker
of one session paraphrased this concern with his question "Where
is the 'M' in MTCT (mother-to-child transmission)?" A short-course
treatment is basically an intervention that uses the woman's body
to deliver treatment to the fetus. It is of no benefit to the woman
and as stated above, may increase viral resistance. This could actually
make things worse for the woman by limiting future treatment options.
In addition, it was noted that only providing MTCT interventions
without continued treatment for the mother will increase the number
of AIDS orphans who frequently become street children. With the
number of AIDS orphans worldwide at over 10 million, it seems in
the best interests of the infants and the communities to address
the mother's health needs. (Session Sy03.)
Dr. Gray, an investigator in many of the South African studies,
posed several questions. Is it ethical to implement MTCT interventions
without treating the mother? Is it ethical not to offer voluntary
testing and counseling if there are no treatment options? Is it
ethical not to inform pregnant women they are at risk for HIV? She
advocated that women have a right to information and education,
no matter what their circumstances are. And while there are ethical
dilemmas to overcome, there are also viable interventions to prevent
MTCT right now. She concluded by stating, "let us not find another
reason not to prevent MTCT." (Session Sy03.)
One such dilemma relates to breast feeding. While the short-course
interventions may prevent MTCT at birth, in most cases the protective
benefit seems to fade with time. This effect is most marked in the
PETRA study. PETRA is a very large multi-site African study evaluating
several different short-course AZT/3TC regimens. The majority of
mothers in the study breast fed (70%). PETRA basically demonstrated
that the two-drug combination initiated at 36 weeks, during delivery
and for one week postpartum for mother and infant reduced transmission
by 50% at six weeks to 9.2% when compared to placebo. However, more
recent data from Durban indicate that this benefit is essentially
lost during breast feeding. At month 18, there was no statistically
significant difference between any of the treatment arms when compared
to placebo arm: rates of MTCT had risen to 20% to 25% in the treatment
arms compared to 26% in the placebo arm. (Abstract LbOr5.)
The high cost of formula, social stigma associated with not breast
feeding and lack of sanitary conditions make formula feeding an
infeasible option for many women in the developing world. A recent
study done by Dr. Anna Coutsoudis has for this reason looked at
exclusive breast feeding as a means to reduce post-delivery MTCT.
In exclusive breast feeding, mother's milk is the only intake the
child has for the first six months of life. In mixed feeding, mother's
milk is supplemented by juice, water, and solids. In her study,
Dr. Coutsoudis compared rates of MTCT among 551 HIV- positive women
who were divided into exclusive breast feeding and non-breast feeding
arms. Her study found that exclusive breast feeding for three months
compared to mixed breast feeding lowers risk of MTCT by 44%. Dr.
Coutsoudis said that "mixed" breast feeding had the potential to
introduce contaminants, which could irritate the babies' stomach
lining and allow easier access of the virus through the babies'
gut. (Abstract LbOr6 and Session DB05.)
While Coutsoudis' results are culturally appealing for many women,
there is also contradictory evidence that suggests that exclusive
breast feeding may not have a protective effect. Exclusive breast
feeding needs further evaluation before it can be identified and
promoted as a means to reduce MTCT in the developing world. Additional
technologies are being developed to pasteurize expressed milk (LbPp122)
and to add alkyl sulfides to inactivate HIV in expressed milk (LbPp123),
which may offer other options. Breast feeding of any kind is not
recommended for women in developed countries who have access to
formula.
In Africa the rate of MTCT is estimated at 21-43%. It is irrefutable
that many of the short-term treatments studied can reduce these
rates significantly. Widespread implementation of these regimens
would have a huge impact on the hundreds of thousands of HIV-positive
infants born in the developing world each year. The South Africa
government and others have been presented with compelling evidence
to act. While the breast feeding debate will continue and the emergence
of drug resistance requires further research, there was a resounding
consensus at the conference that these uncertainties should not
interfere with the implementation of comprehensive MTCT-prevention
programs. It should also be clear that preventing MTCT is only the
first step and progress must be made towards providing care for
the mother herself, so that the M is no longer missing from MTCT.
As demonstrated by studies from industrialized nations, which show
rates MTCT dropping lower and lower towards zero, what is best for
the mother's health is best for the baby.
Footnotes
1. UNAIDS Fact Sheet HIV/AIDS in Africa ww.unaids.org/fact_sheets/files/Africa_Eng.html
2. UNAIDS Report on the Global HIV/AIDS Epidemic, June 2000, p.
126
3. Landesman S et al. The New England Journal of Medicine. June
20, 1996; 334(25):1617-23
4. Guay LA et al. The Lancet. September 4, 1999; 354(9181):795-802
5. Wood E et al. The Lancet. June 17, 2000; 355(9221): 2095-100
6. Department of Health and Human Services, July 14, 1999: http://www.niaid.nih.gov/cgi-shl/simple/release.cfm
The Body Habitus in
Durban
By Gabriel Torres, M.D.
The mystery of change in body habitus, accumulation of fatty tissue
in areas such as the trunk, the neck, the breasts and the upper
back accompanied by atrophy of adipose tissue in the face (Bichat's
fat pad), the limbs and the pelvis/butt, was not resolved in Durban.
But various studies addressed its probable etiology, pathogenesis,
prevalence, and some studies addressed potential preventive strategies
with a handful actually suggesting a therapeutic intervention. A
panel of experts did not reach a consensus opinion on the definition
of the syndrome, and controversy reigned when it came to how to
use diagnostic tools to evaluate the syndrome. Patients tend to
report more severe findings associated with the syndrome as compared
to physicians, as was noted in a study conducted by Toby Kasper
from GMHC (Abstract 1380). Anthropomorphic measurements like waist
to hip ratio lacked specificity (Abstract 4246) in one study, whereas
brachial and malar sonography had 85-88% sensitivity and 75-84%
specificity (Abstract 4280); others argued for simpler office procedures
such as measuring the waist circumference or obtaining serial photographs
of patients to follow their change in body habitus.
Etiology and Pathogenesis
Various old theories which postulated a homology between the protease
enzyme and several proteins involved in fat metabolism have been
discarded as new studies indicate a potential role for mitochondria
toxicity in the pathogenesis of the fat mal-distribution and the
the metabolic irregularities. Mitochondrial toxicity is an acquired
decrease in mitochondrial function (mitochondria are organelles
within cells which produce ATP, the energy substrate of most living
organisms) induced by NRTIs. This can result in several clinical
syndromes like myopathy, neuropathy and lactic acidosis and possibly
fat and lipid metabolism aberrations such as adipose tissue loss.
Mallal and Nolan from Perth,Australia, showed in a late breaker
poster session (LB7054) impressive electron microscopy pictures
of adipose tissue, taken from patients with clear symptoms of lipodystrophy.
Both in patients treated with or without protease inhibitors (but
always NRTIs), there were clear abnormalities in mitochondrial structure,
together with an accumulation of lipid droplets (steatosis), compared
with control specimens. Furthermore, there was an unexplained deposition
of granular material on the inner aspect of the adipocyte membrane.
Nucleoside analogues have been associated with lactic acidosis and
hepatic steatosis, which is thought to relate to mitochondrial dysfunction
caused by these agents inhibiting mitochondrial DNA polymerase gamma.
This problem has been reported with all the available nucleoside
analogue combinations. Inhibition of this enzyme has been suggested
to also be important in the pathogenesis of fat redistribution syndrome.
A difference in relative incidence of lactic acidosis or hyperlactatemia
between combinations has not been established. In a cross sectional
survey of 211 asymptomatic patients, 161 (76%) of whom were on nucleoside
analogue therapy, mild hyperlactatemia (defined as 2.1-5mmol/l)
was present in 23% of treated and 8% of untreated patients. Serious
hyperlactatemia (>5mmol/l) was observed in only one patient, which
normalized without alteration of therapy. Of the patients with hyperlactatemia,
19% of ZDV recipients therapy, and 28% of d4T recipients had hyperlactatemia
(Abstract 1234). The presence of elevated lactate in the absence
of therapy is intriguing but may reflect laboratory issues, sampling
variation (for example, use of cuffs or not), use of other mitochondrial
toxins (such as alcohol), familial mitochondrial disease, recent
exercise or the possibility that HIV infection alone may impact
mitochondrial function.
A similar survey of 70 treated patients found lactate levels were
>2.1 in 36% of patients and the anion gap widened in 19%. Three
of four patients with lactate >3mmol/l and an anion gap of >12 had
symptoms suggestive of drug toxicity such as fatigue, weight loss
or myopathy (Abstract 1233). In eight patients with clinical lipodystrophy
who were exercised to assess oxidative and glycolytic capacity in
skeletal muscle tissue using ergometer cycling, oxygen consumption
(VO2) and blood lactate (L) was measured. Before and after exercise,
muscle biopsies were obtained to measure activity of citrate synthase
(CS) and hydroxyacyl-CoA dehydrogenase (HD) to assess mitochondrial
oxidative capacity. The HAART treated HIV patients performed less
work than healthy controls and had significantly higher baseline
and post exercise lactates. Muscle biopsy data did not differ from
controls. The absence of muscle abnormalities suggest that lactate
elevations may have related to diminished hepatic clearance of lactate
rather than excess production (Abstract 1232).
Bernasconi et al. (Abstract 703) confirmed earlier observations
from other cohorts of an association between the development of
lipoatrophy and the exposure to either d4T (OR 2.1) or d4T/ddI (OR
1.5). They furthermore showed a significant association between
lipoatrophy and increased lactate levels, which was lacking in the
situation of fat accumulation. In a multivariate analysis for fat
accumulation only age >41 and intravenous drug use were associated.
The association of fat loss and older age was noted by various studies,
as were the use of stavudine or indinavir or ritonavir and the overall
duration of HIV infection (Abstracts 704, 4215, 4245, 1382, 4242).
The SMART study (systematic monitoring of antiretroviral therapy)
cohort of 207 subjects in Amsterdam found that only duration of
ART, older age and weight at the time of initiation of HAART therapy
were significantly associated with d4T use (Abstract 4247). In this
study, however, the prevalence of lipodystrophy was low (15.5%)
and the patients changed meds liberally due to side effects etc.
or clinical parameters. Thus it was difficult to implicate a single
class of drugs.
All in all, the weight of the evidence seems to suggests that d4T
is implicated in fat loss especially in older persons. On the other
hand, protease inhibitors are more strongly associated with fat
accumulation and lipid disorders as was demonstrated by several
studies (Abstracts 4281, 4232) where patients on PI-containing regimens
were compared to those on PI-sparing regimens and found to have
more frequent elevations in triglycerides and cholesterol and truncal
adiposity. Women seem to experience more fat accumulation than men,
who seem to suffer from more fat loss. This was reported by three
groups of investigators (Abstracts 4212, 4273, 4272); one found
fat loss in 44% of males and 23% of females. The difference among
the genders remains unexplained.
Treatments
Various investigators in Durban discussed treatment for the various
aspects of the lipodystrophy syndrome, although a treatment for
the underlying cause or a preventative strategy is still unavailable.
The use of protease-sparing regimens was actively discussed and
overall seemed to show a beneficial effect in the incidence of the
syndrome without a negative effect on clinical or virological outcome,
although the results were all preliminary and long-term outcome
data are still not available. Lipid -lowering agents are being actively
used to treat the lipid disorders and should be used with caution
as many will interact with HAART; simvastatin levels, for example,
can be elevated 2,500-fold in the presence of ritonavir and saquinavir.
Thus pravastatin is recommended for treatment of hypercholesterolemia
since it does not require the cytochrome p450 system for metabolism
and was shown in several studies to effectively lower cholesterol
levels in lipodystrophy patients (Abstracts 1438, 4277).
Treatments for fat atrophy are mostly cosmetic in nature, with
cosmetic surgery and implants of human collagen or autologous fat
implants being the most common, none of which received much attention
in Durban. Stopping the HAART regimen was studied at the NIH among
26 male patients with viral loads <400 copies/ml sustained for one
year; after 5.9 weeks of stopping therapy declines in lipid levels
were noted (Abstract 4221), but there were no changes in insulin
resistance and anthropomorphic measurements.
Deborah Cotton reviewed six studies that evaluated changing from
a protease inhibitor to an NNRTI-containing regimen with a total
of 307 patients and noted a mean decrease in cholesterol of 16%
and in triglyceride levels of 27.6% in six months. Changes in body
habitus were not uniform. In one sudy, where the PI was substituted
for nevirapine, there were declines in serum triglycerides and increases
in HDL cholesterol levels, but no change in LDL cholesterol and
only a trend in reduction in fat as measured by DEXA.
These studies all are limited by the fact that they were uncontrolled
and only the PI was substituted and lipodystrophy was already present,
which may be irreversible once established, despite the potential
causative agent being removed. Since it is unclear which of the
classes of drugs are involved, or whether both are responsible,
the inconsistent changes are not entirely unexpected.
Another potential agent for treatment of fat accumulation, which
received some attention in Durban, was recombinant human growth
hormone Serostim. This writer described 36 patients with lipodystrophy
treated with Serostim for an average of 16 months, of whom 89% responded
within 4 to 12 weeks with reductions in truncal adiposity, breast
size and buffalo humps, without any significant changes in lipid
levels or peripheral or facial fat loss (Abstract 4234). Bioelectric
impedance analysis (BIAs) and serial photographs were used to follow
changes in body habitus. Side effects included hyperglycemia, joint
pains and carpal tunnel syndrome, most of which were reversible
upon drug discontinuation or dose reduction. Most patients relapsed
once the drug was stopped and required maintenance therapy with
low dose Serostim to maintain the lipolytic effect.
Another investigator, Engelson, reported on the use of growth hormone
and was able to demonstrate a 46% decrease in visceral adiposity
and an 18% decrease in subcutaneous fat using DEXA and total body
K+ (Abstract 1437). In a placebo-controlled trial Furrer showed
that growth hormone reduced mean truncal fat by 2.4 kg, total mean
fat by 2.6 kg but found no effect in subcutaneous fat or fasting
lipid levels. All the effects were reversed upon drug discontinuation,
except in one patient who continued arduous exercise in the gym
(Abstract LB114).
The main problem associated with growth hormone in addition to
the adverse effects is its exorbitant cost, which puts it out of
reach to most patients; in addition its lipolytic effects may worsen
the fat loss in the periphery or the face, yet to date it is the
only agent which has a definitive effect in reducing the visceral
and truncal fat accumulation which is most troublesome to patients.
In terms of the long-term cardiovascular complications of hyperlipidemia
little was reported in Durban that would alter our thinking in terms
of early intervention with HAART. One study suggested an abnormal
carotid artery intima-medial thickening in patients with lipodystrophy,
yet not significantly (Abstract 761). In addition, another study
did not find the incidence of myocardial infarction to be significantly
elevated although the length of follow-up was not adequate since
it can take decades before the effects of hypercholesterolemia and
hypertriglyceridemia are evident. In any case, elevated lipid levels
should be treated aggressively in HIV-positive patients as their
longevity is bound to be longer or as long as those of middle age
or older HIV negative adults who develop this disorder during late
adulthood.
One agent which recently received a lot of attention was metformin,
an insulin sensitizing agent which has been used in diabetes mellitus
as an oral hypoglycemia agent. The published study in JAMA was a
pilot study of 26 individuals with HIV-associated lipodystrophy
syndrome.1 The authors report that metformin (500 mg twice daily)
as compared to placebo reduced waist circumference, reduced visceral
abdominal fat but no change was seen in VAT-SAT (subcutaneous adipose
tissue) ratio. There was no significant effect of treatment on waist-hip
ratio. Sixty-four percent (n=9) complained of mild to moderate diarrhea,
which was reported to improve for most within 4 weeks, whereas 3
(27%) of 11 placebo patients experienced new or worsening diarrhea.
There was no increase in lactate level associated with metformin
therapy and both groups had mild decreases in lactate levels at
three months. All patients in this study were receiving concomitant
NRTIs; therefore, the absence of a significant effect on lactate
levels provides some reassurance that low-dosage metformin can be
used safely in this population.
Overall, our understanding of the lipodystrophy syndrome has improved
after Durban, despite the innumerable of unanswered questions; practical
diagnostic tests and procedures and simple interventions or strategies
may help avert the complications or at least stall them temporarily.
Early intervention in the recognition and treatment of the syndrome
is required as long-standing aberrations in lipid metabolism or
grotesque body habitus deformities due to fat accumulation or loss
are bound to be irreversible.
Reading Durban
By Derek Link
Few Americans who attended the Durban AIDS meeting left without
a profound of sense of transformation. AIDS activists marched through
the streets of Durban, and the country's newspapers and televisions
were dominated by AIDS coverage. The American advocates who attended
the meeting spoke of feeling energy similar to the beginning of
AIDS activism here, but in a wholly different context and with a
wholly different set of challenges. Many left with broadened notions
of what is possible in the fight against the global AIDS pandemic.
Unfortunately (and shamefully), many prominent American researchers
simply did not go, depriving the conference attendees of their scientific
expertise and depriving themselves of an experience of profound
importance in the global fight against this disease. Most notable
among the no-shows were Dr. Robert Schooley, chairman of the US-funded
AIDS clinical Trials Group, the $70 million network that develops
new treatments for AIDS and its related conditions, and Dr. Constance
Benson, chair of the ACTG's scientific agenda committee.
The lack of high-level scientific participation was evident in
the scientific proceedings. The abstracts from the conference are
notably light, with most HIV science having shifted to the annual
retrovirus meeting held early each year in the United States. Nevertheless,
the conference proceedings did contain much behavioral data, and
many presentations by researchers from developing countries that
discuss the problems and opportunities they face.
Writing about the science at a meeting where context was more important
than content required a new approach. To make some sense of the
proceedings, this article provides an overview of presentations
by New Yorkers who attended the Durban meeting, and has a particular
focus on research related to New York's gay male communities.
New York in Durban
Researchers at Columbia University submitted 48 abstracts to the
Durban meeting, more than any other institution in New York. The
abstracts included several studies of zidovudine use in children
born to HIV-infected mothers, and a large number of behavioral studies
conducted in an HIV-infected population in the Rakai district of
Uganda. Physicians at Harlem Hospital, which is affiliated with
Columbia University, reported on a peer support program at their
hospital for antiretroviral drug adherence. (Abstract WePeD4577.)
The hospital trained 14 HIV-infected peer educators to serve as
role models and liaisons with other HIV-infected patients at the
hospital. The hospital staff report that, after 14 months, the program
has assisted 52 patients, and has been a success.
The New York State AIDS Institute submitted eight abstracts to
the conference. One abstract (Abstract ThPeB4982) reported on the
progress of a treatment adherence demonstration project that enrolled
over 600 HIV-infected patients with advanced immune-suppression.
One abstract (Abstract ThPeC5326) described the current epidemiology
of perinatal HIV infection in New York, and another abstract (Abstract
MoPeC2359) reported on the success of further reducing perinatal
HIV transmission in New York, but pointed to a lack of universal
prenatal care for all pregnant women as a crucial barrier to further
success.
Other abstracts submitted by the state health department looked
at the design of HIV prevention programs for older adults (Abstract
TuPpD1255) and described prevention projects for transgendered people
(Abstract WePeE4927). One abstract looked at HIV RNA viral load
levels over time in cohort of 1,284 HIV-infected women (Abstract
MoPeB2182). This study found low CD4 levels were associated with
the development of AIDS-related conditions, and high viral RNA levels
were correlated with faster progression to AIDS. "These findings
may help guide HIV treatment strategies" the authors conclude. Another
abstract reported on the decline of HIV prevalence among intravenous
drug users in New York, and credits this, in part, to syringe exchange
programs (abstract MoPpD1124.) The health commissioner of New York
reported (Abstract MoPeB2161) on the importance of maintaining confidentiality
of state-collected HIV surveillance data.
The New York City Health Department submitted seven abstracts to
the conference, two of which (on successes in perinatal prevention
and needle exchange) were submitted jointly with the state health
department. The city health department presented information on
a community-based prevention program for transgendered people (Abstract
ThPeD5682.) The city also reported on trends in HIV prevalence among
gay men, which is reported below.
The city health department reported a study of foreign-born HIV-infected
people in New York City (Abstract MoPeC2360). This is an issue of
some considerable importance in New York City, where about 40% of
the population is foreign-born. The study found that HIV-infected
people who are foreign-born present for medical care at a far more
advanced stage of immune suppression. The city health department
also reported on the growing number of perinatally HIV-infected
children who are living into adolescence (Abstract TuPeC3351). With
improved treatments, more than 7,000 HIV-infected children are likely
to enter adolescence over the next five years, according to the
study.
The city health department reported on trends in AIDS mortality
in New York from 1990 to 1998 (Abstract TuPeC3385). During this
period, deaths from AIDS declined by 88%, from 406 per 1000 persons
to 44 per 1,000 persons, the city health department reported. Deaths
from all non-AIDS-defining causes among reported AIDS cases declined
by 82% from 74 per 1,000 in 1990 to 13 per 1,000 in 1998, with the
largest declines for pneumonia/influenza (92%), infectious/parasitic
diseases (89%), malignancy (85%) and cardiovascular diseases (79%).
In 1998, mortality from AIDS was higher among females than males,
higher among blacks and Hispanics than whites, higher among male
heterosexuals than female, and higher among intravenous drug users
than men who have sex with men.
New York's Gay Men in Durban
Most observers agree the scientific reports at the Durban conference
were light, emphasizing behavioral research over new drug development
and basic science. Perhaps that makes all the more surprising the
dearth at the conference of behavioral information about the HIV
epidemics ravaging New York's gay male communities. Few populations
in the industrialized world have HIV prevalence rivaling those of
gay men in New York. But this was not evident from reading the scientific
reports at Durban. Of 4,958 abstracts submitted for the conference
proceedings, only 24 mentioned gay men in New York at all (0.004%),
and most of these did so only to say New York's gay men had been
receiving too much attention.
Despite all this, a few studies about New York's gay male epidemics
were presented. One of the most interesting abstracts on New York's
gay male population came from Ron Stall at the University of California
at San Francisco. (Abstract ThOrC716.) His team has developed a
new method of measuring HIV prevalence and HIV risk factors in gay
males using validated telephone survey techniques. Dr. Stall conducted
the first household-based sample of gay residents in four cities
with a known density of gay men greater than 1.6%, including New
York. The researchers use a random dial phone methodology, and a
validated interview technique, to determine if the residents reached
on the phone are men who have sex with men. The researchers asked
about sexual and drug using practices, and also HIV testing and
infection. The survey methods have been validated by in-person HIV
testing using oral testing techniques in a subset of the sample.
The survey found an overall HIV prevalence of 18% in the complete
sample of 2,881 men. Validation by oral HIV testing techniques found
these self-reported results to be 100% specific and 98% sensitive.
HIV prevalence was significantly higher among men with a history
of injection drug use, men who reported at least weekly non-intravenous
drug use, less closeted men, men with lower educational levels,
African American men, men of middle age or older, and homosexually
identified men.
The New York City Health Department reported on HIV seroprevalence
trends in men who have sex with men who sought treatment at city-funded
sexually transmitted disease clinics from 1990 to 1998 (Abstract
WePeC4374). During this period, 3,640 men who have sex with men
attended a city STD clinic, 42% of whom were black, 16% Hispanic,
30% white, and 10% of other or mixed race/ethnicity. Two-thirds
were over 30 years old, and 19% were over 40. Overall HIV prevalence
declined from 47% in 1990 to 19% in 1998, matching the seroprevalence
level found in Stall's telephone survey.
Among racial groups, HIV prevalence declined from 34% in 1990 to
10% in 1998 among white men, 47% to 13% among Hispanic men, 56%
to 32% in African American men, and 44% to 23% in bisexual men.
Men with gonorrhea or syphilis had stable HIV prevalence over the
study period, at 40% to 50%. HIV prevalence in men with all other
STDs declined from 44% to 15%. HIV prevalence in men with no STD
dropped from 48% to 10%. In the study, HIV infection was most heavily
associated with black race/ethnicity, age under 25 years, and a
diagnosis of gonorrhea or syphilis. Men with gonorrhea or syphilis
were less likely to accept HIV testing than men with other diagnoses,
gonorrhea was diagnosed four times more frequently in seropositive
than seronegative men, and syphilis was diagnosed twice as often
in seropositives as seronegatives. The city health department concludes
that HIV prevalence in these men has declined significantly during
the study period, but wide racial disparities were observed. The
health department advises the use of gonorrhea and syphilis as sentinel
markers for HIV risk.
Gay and lesbian youth in New York City remain at high risk for
HIV, because of their sexual and drug-taking behaviors, concludes
Joyce Hunter of the Center for HIV Clinical and Behavioral Studies
at Columbia University, who interviewed 72 gay male adolescents
and 52 lesbian adolescents. (Abstract TuPeC3485.) The youth, who
were recruited through youth services agencies, were asked about
their sexual and drug-taking behaviors in the previous six months.
The interviews found three-quarters of the young men surveyed had
multiple sex partners in the previous six months, and one-quarter
had had unprotected anal sex. Among the young women interviewed,
one-quarter had had unsafe intercourse with a male partner in the
previous six months. Virtually all the youth surveyed (95%) had
used drugs or alcohol in the previous six months.
Most gay and lesbian youth in New York who are at risk for HIV
infection do not discuss HIV with their sex partners, nor do they
disclose their HIV status or enquire about their partner's, concludes
Ron Klitzman, another researcher at Columbia's Center for HIV Clinical
and Behavioral Studies, who questioned 144 gay and lesbian adolescents
(Abstract WePeD4655.) About 60% of the young men and women do not
discuss HIV with their same-sex sex partners, and about three-quarters
do not discuss HIV with opposite-sex sex partners. One-third of
the adolescents usually do not use condoms during anal or vaginal
sex, and about one-half use condoms inconsistently. Factors associated
with increased discussion and disclosure of HIV among the adolescents
was "high self esteem," previous HIV testing history, and discussions
with a parent about HIV. The study found no gender differences,
except that young males were somewhat more likely to have been tested
for HIV.
Young Latino men who have sex with men in New York feel more connected
to their ethnic community than to the gay community, and are relatively
open with their friends and mothers, but not their fathers, about
their sexual practices, concludes A. San Doval, of the Educational
Development Center, who surveyed a random sample of 528 young men
in New York City. (Abstract ThPeD5602.) The men were recruited at
gay venues outside the "central gay-identified area of lower Manhattan."
One-third of the men were under age 21, and almost half had been
foreign-born. Almost 60% of the young men said most of their friends
knew they had sex with men, and 53% said their mothers knew. About
one-third felt a strong connection to the organized gay community,
and another one-third felt no connection at all. Two-thirds said
they felt very connected to their ethnic community. The author concludes
ethnic affiliations are strong, pointing to the need to take advantage
of these community ties in targeting HIV prevention services.
Gay identity among young Latino men who have sex with men in New
York does not promote safer sexual behavior, according to another
analysis of the same survey population by the Educational Development
Center (Abstract WePeD4749.) Over half of the sample had a high
school education or less, most (70%) identified as gay, 21% identified
as bisexual, and the rest were unsure. Unsafe sex was very common.
Three-quarters of the men had unsafe anal sex with another man within
three months of the survey period. No differences in behavior were
found between gay-identified and bisexual men in this survey.
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