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? Absolutely nothing!

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?

Summary

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)!

Conclusion

These observations are consistent with the hypothesis that antiretrovirals are killing people just as fast as poverty and malnutrition.

Notes:

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?"

References:

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; 324:193-6.

4. CDC. Year end HIV/AIDS Surveillance Report 1995; Vol 7:No. 2.