NEW STUDY SHOWS AIDS DRUGS EQUALLY EFFECTIVE AS POVERTY AND MALNUTRITION
By Rodney Richards
26 March 2002
If antiretroviral drugs are dramatically improving survival in those
infected with HIV, then shouldn't we see dramatically reduced survival in
those who have no access to these drugs? Surprisingly, this is not what is
observed. In the March 8, 2002 issue of the journal AIDS, scientist from
the Medical Research Council, and the Uganda Virus Research Institute in
Uganda (MRC/UVRI), report that untreated HIV infected Ugandans are surviving
"considerably longer than has been expected."(1)
In fact, this is an understatement. The untreated Ugandans in the above
study are actually surviving just as long as their medicated counterparts in
the developed world, according to data published in the April 1, 2000 issue
of The Lancet.(2) This latter study was conducted by the Collaborative
Group on AIDS Incubation and HIV Survival Group (Collaborative Group), which
analyzed data from 13,030 individuals (with known dates of seroconversion)
from Europe, North America, and Australia to estimate time from
seroconversion to AIDS and death.
Specifically, "median time from seroconversion to death was 9.8 years"(1) in
the Ugandan study, as compared to 10.1 years for aged matched individuals in
the Collaborative Group study; and median time from seroconversion to AIDS
was 9.4 and 9.3 years for the two studies, respectively (see Note 1).
Even more miraculously, for individuals infected at age 15-24 in these
studies, 10-year survival was substantially better in antiretroviral-free
Ugandans than it was in their medicated counterparts living in Europe, North
America and Australia (78% vs 66%, see note 2).
Could it be that these particular rural Ugandans are living in abundance
with good nutrition and the necessary resources to provide for an
environment conducive to fending off the opportunistic infections waiting to
take advantage of their failing immune systems?
The authors give us the answer in a separate report, which was published two
months earlier under the covers of a different journal (BMJ). "Most of the
population" in their study area "lives in poverty; food is often in limited
supply, there is no electricity, and there is poor access to any, let alone
clean, water. Malaria is endemic, and infections other than HIV, especially
bacterial infections, are common."(3)
Interestingly, the BMJ publication doesn't even talk about time to AIDS or
death. Rather it focuses on symptoms in these HIV infected individuals and
paradoxically concludes, "[d]isease progression associated with infection
with HIV-1 seems to be rapid in rural Uganda." Only in the world of
HIV/AIDS can "rapid" disease progression be correlated with "considerably
longer" survival. The apparently schizophrenic conclusions in these two
publications, which are derived from the same patient population, are
discussed further in Note 3.
The authors of the Ugandan study(1) attempt to divert attention from the
extraordinary survival rates observed in their subjects by emphasizing they
are, "comparable to survival times in industrialized countries *prior* to
the widespread use of antiretroviral therapy." (*emphasis* mine) Well, this
is technically true, but only because survival times haven't changed since
the widespread use of antiretroviral therapy!
The Collaborative Group study analyzed data for 13,030 individuals who
seroconverted in the pre-HIV-era (before 1983), the prophylaxis-era
(1983-1987), the AZT-era (1987-1990), the monotherapy-era (1990-1993), and
the combination therapy-era (1993-1996); and contrary to all expectations,
they inform us, "[we] found no evidence of a difference in survival or time
to the diagnosis of AIDS for individuals who seroconverted in 1983-96."(2)
How can this be? First, we were told prophylaxis against PCP and MAC slows
progression to AIDS and death, then we were told AZT dramatically slows
progression to AIDS and death further yet, and then we were told combination
therapy dramatically slow progression to AIDS and death even further yet!
But, what do we see when we put all of this additive benefit together?
Well this is not quite true, for there was one group in the Collaborative
Group study that did enjoy significantly better survival; namely, those who
seroconverted before 1983. So technically, it is not fair to say
prophylaxis, mono-therapy, and combination therapy did "nothing." Those who
seroconverted in years when these drugs were immediately available actually
did significantly worse. The authors offer the following incoherent
rationalization to account for this: "The apparently better survival for
individuals seroconverting before 1983 may be an artefact, because these
individuals seroconverted before the discovery of HIV-1 as the causative
agent for AIDS."
Rather than focusing on the fact that their data offers 13,030 examples
demonstrating a complete lack of benefit to any of the antiretrovirals used
alone or in combination up to 1996, the authors instead present this data as
a summary of the situation, "before the widespread use of [HAART]."
Apparently holding out the implication that now things are most certainly
different. Yet the authors offer no data of their own, or even a reference
to a single publication, which tells us how patients who seroconverted in
the HAART era are doing.
Today, nearly two years later, the PubMed data base still list no published
comments on the results of the Collaborative Group study; and I am still
unaware of any publication that reports data for survival or time to AIDS in
persons with known dates of seroconversion after 1996, in the era of
ostensibly better HAART therapy.
Even if such data were to become available, and even if the data looked
good, were still left with the fact that the 513,486 AIDS patients reported
to the CDC(4) prior to 1996, needlessly consumed billions of dollars worth
of useless antiretrovirals that seriously compromised their quality, and
perhaps even quantity, of life.
Do these more than a half-million individuals, or their families and loved
ones, deserve to know that all the promised benefits of these drugs, which
were aggressively promoted by the pharmaceutical industry, our public health
institutions, and uncritical journalist, were nothing more than illusions?
That the only thing real that resulted from their dedicated compliance to
consuming these chemicals was the compromised quality of life and
debilitating side-effects they suffered? Or do we simply marginalize and
divert attention from their senseless pain and suffering by shining the
light of hope on the new unproven drugs of the HAART-era?
Aside from the tragic story implicit in the results of the Collaborative
Group study; they do, never the less, help us understand why untreated
Ugandans are surviving just as long as their infected counterparts in the
developed world. Namely, according to the Collaborative Group study, the
drugs are demonstrably worthless at best. But still, even if these drugs
are worthless, shouldn't HIV positive Americans and Europeans who have full
access to food, water and health care still be doing far better than their
impoverished Ugandan counterparts? Is there anything that can explain the
remaining part of this paradox?
The Ugandans enrolled in the above studies did have access to regular
check-ups, diagnostic testing, and free medication for routine health-care,
which might have contributed to survival. However, when the researchers
studied matched HIV positives outside of the study cohort, who did not have
access to these amenities, survival times were no different. A
"disappointing" finding for which, "we do not have a good explanation,"(1)
according to the authors. Perhaps access to health-care and medicine is of
little use to the malnourished with no access to food or clean water?
Perhaps it be possible that the Ugandans in these studies are not surviving
surprisingly long, but rather, the subjects in developed countries on
antiretrovirals are actually dying surprisingly fast. Perhaps these
antiretrovirals are not worthless, but are actually harmful to the same
degree as poverty and malnutrition.
To check this hypothesis, I would propose giving some of the Ugandans in the
above studies access to food and water. I would predict we would see their
median survival significantly surpass that of their medicated counterparts
in the developed world. It's not unethical to give Africans food is it?
Median time from seroconversion to AIDS and death in poor, starving
rural Africans (without access to health care, purified water or
electricity) living in the Masaka District of Uganda (where malaria,
dysentery and measles are endemic) is no different than that observed in
Europeans, North Americans, or Australians who have full access to proper
nutrition, health-care, "live-prolonging" antiretrovirals, and prophylaxis
against opportunistic infections (OI)!
These observations are consistent with the hypothesis that
antiretrovirals are killing people just as fast as poverty and malnutrition.
1. Progression to AIDS and death in the Collaborative Group study was
significantly correlated with age at seroconversion. Therefore, the authors
report disease progression according to age groups. Median time to AIDS
ranged from 11.0 to 5.0 years for those aged 15-24 to 65+, respectively; and
median time and death ranged from 12.5 to 4.0 years for those aged 15-24 to
65+, respectively. Based on the age distribution of subjects in the Ugandan
study (1), age matched median time to AIDS and death is calculated to be 9.3
and 10.1 years, respectively, in the Collaborative Group study.
2. This data is approximated from the graphs in the respective
publications. See Fig. 2 in the Ugandan study, and Fig, 1 in the
Collaborative Group study.
3. The Ugandan studies use the WHO Staging system to define disease
progression. (WHO. Wkly Epidemiol Rec 1990; 65:221-8.) Unlike the Bangui
definition of AIDS (WHO. Wkly Epid Rec 1986; 61:72-73.), which is based on
clinical symptoms without an antibody test, the WHO staging system requires
a positive anti-HIV test. It then attempts to gage disease progression
according to four Stages. Stage 1: asymptomatic; Stage 2: mild symptoms,
including weight loss of as little as 5%; Stage 3: weight loss greater than
10%, or treatable opportunistic infections; and Stage 4, which is synonymous
with AIDS. Stage 4 includes many, but not all of the illnesses used by the
CDC to define AIDS.
The staging system is progressive, hence when a person progresses to a
higher stage, they cannot go back even if the condition is resolved. So
when the authors report, "only 17% of participants remained symptom-free
five years after seroconversion," this is not striking. In fact, the vast
majority of participants may actually be symptom-free as we speak. A single
bout of sinusitis, dermatitis, or bacterial infection, or even a 5% weight
loss (in a month), over this 5 year period leaves the subject classified as
symptomatic, regardless if they recover or not.
The fact that disease progression to Stages 2 and 3 is remarkably rapid,
while disease progression to Stage 4 (AIDS), or death, is remarkable slow,
leaves one wondering, "of what value is this Staging system?"
1. Morgan D et al. HIV-1 infection in rural Africa: Is there a difference in
median time to AIDS and survival compared with that in industrialized
countries? AIDS. 2002; 16:597-603.
2. Collaborative Group on AIDS incubation and HIV Survival including the
CASCADE EU Concerted Action. Time from HIV-1 seroconversion to AIDS and
death before widespread use of highly-active antiretroviral therapy: a
collaborative re-analysis. Lancet 2000; 355:1131-37.
3. Morgan D et al. Progression to symptomatic disease in people infected
with HIV-1 in rural Uganda: prospective cohort study. BMJ. 2002 Jan 26;
4. CDC. Year end HIV/AIDS Surveillance Report 1995; Vol 7:No. 2.