|HIV drugs||AZT/PIs||Ineffectiveness||Disease progression|
|Uniform risk of clinical progression despite differences in utilization of highly active antiretroviral therapy:Swiss HIV Cohort Study.|| ||Junghans C et al.
| ||“During 7007 person-years of follow-up 2285 (69%) patients started HAART and 318 (10%) developed a new AIDS event. In multivariable analysis controlling for CD4 cell count, viral load and disease stage at baseline, the probability of starting HAART was lower in injection drug users compared with men who have sex with men... The deferred initiation of therapy in these patients does not, however, appear to translate into an increased risk of clinical disease progression.”|
| ||AIDS. 1999 Dec 24;13(18):2547-54.||1999|
|Long-Term Highly Active Anti-Retroviral Therapy in an Anti-Retroviral Experienced Population.|| ||Ramirez CM, Gottlieb MS.
| ||“We examined 304 anti-retroviral-experienced patients who were placed on HAART for a period of 18 months... At baseline, 39% were classified as asymptomatic, 33% were symptomatic, and 28% had an AIDS defining illness. The HAART regimens included 3-5 anti-retroviral agents at least one of which was a protease inhibitor...After 18 months, 14% of the population remained asymptomatic, 10% of which had an undetectable viral load. 39% were symptomatic and 47% of the population had an AIDS defining illness... [i.e. HAART did not prevent disease progression]”|
| ||AIDS Weekly Plus. 1999 Jun 28.||1999|
|Gap between biology and reality in AIDS.|| ||Carr A, Cooper DA.
| ||“Despite biological plausibility, studies of protease inhibitors which evaluate survival benefit have not yet been carried out.”|
| ||Lancet. 1998 Dec 19;352(S5):16.||1998|
|Survival in HIV-infected patients who have received zidovudine: comparison of combination therapy with sequential monotherapy and continued zidovudine monotherapy.|| ||Graham NMH et al.
| ||“The median prolongation of survival associated with changing therapy was, at best, 3 to 6 months...Mortality within [3.5-4.9 years, depending on starting CD4 cell counts] was 100%, regardless of treatment group or landmark...Overall long-term survival [in a study comparing AZT monotherapy with various combination therapies] was grim, even among patients who changed therapy; this finding indicates the continued need for newer, more active antiretroviral regimens.”|
| ||Ann Int Med. 1996;124:1031-8.||1996|
|New study shows AIDS drugs equally effective as poverty and malnutrition.|| ||Richards Rodney
| ||Study 1) report that untreated HIV infected Ugandans are surviving "considerably longer than has been expected." In fact, they are actually surviving just as long as their medicated counterparts in the developed world, according to data published in the study 2) 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" 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. 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%) even though "most of the population" in study 1) area lives in poverty; food is often in limited supply, there is no electricity, there is poor access to any, let alone clean, water and where malaria is endemic, and infections other than HIV, especially bacterial infections, are common. 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. Nota : the staging system in study 1) 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. study 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, study 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.|
|Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis.|| ||Collaborative Group on AIDS incubation and HIV Survival including the CASCADE EU Concerted Action.
| ||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."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 except for 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... 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 thousands of AIDS patients reported to the CDC prior to 1996, needlessly consumed billions of dollars worth of useless antiretrovirals that seriously compromised their quality, and perhaps even quantity, of life.|
| ||Lancet 2000; 355:1131-37.||2000|