Numerous clinical trials as well as observational data (i.e. studies from clinical practice) have demonstrated beyond reasonable doubt that the benefits of antiretroviral treatment for people with HIV/AIDS far outweigh their risks. Antiretrovirals are an extremely well tested class of medicines. We present some of the evidence demonstrating that their benefits outweigh their risks here.
The current standard of care for people with HIV indicated for treatment, is a combination of three or more antiretroviral drugs taken everyday for life, known as Highly Active Antiretroviral Treatment (HAART). People with HIV generally do not need to begin antiretroviral treatment until their disease reaches an advanced stage. The World Health Organisation treatment guidelines for resource-limited settings explain when HAART should be commenced and what precise combination of antiretrovirals should be used.
In the United States, the standard of care for adults and adolescents, as well as children, is described by the US Department of Health and Human Services.
In South Africa, the standard of care is described in the Southern African HIV Clinicians Society's antiretroviral treatment guidelines.
Antiretrovirals have also been shown to reduce the risk of women transmitting the virus to their infants. Here are the US guidelines and the World Health Organisation guidelines.
This meta-analysis of 54 antiretroviral clinical trials has demonstrated that:
Using one antiretroviral reduced progression to AIDS or death by 30% against placebo.
Using two antiretrovirals reduced progression to AIDS or death by 40% against one antiretroviral
Using three antiretrovirals reduced progression to AIDS or death by 40% against two antiretrovirals
AIDS denialists say that the risks of antiretrovirals outweigh their benefits. If this is the case, then why do people do better when they take more antiretrovirals? The denialists cannot rationally explain this.
This randomised trial compared patients who took HAART continuously to patients who took structured treatment breaks. The rate of progression to AIDS or death in the continuous treatment arm was half the structured treatment break arm.
AIDS denialists say that the risks of antiretrovirals outweigh their benefits. If this is the case, then why do people who take antiretrovirals all the time do better than people who take them occasionally? The denialists cannot rationally explain this.
This important study demonstrated how effective HAART was in clinical practice. Quoting from the abstract:
"Mortality among the patients declined from 29.4 per 100 person-years in 1995 to 8.8 per 100 person-years in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit ..." [our emphasis]
Using leading-edge statistical techniques, the authors calculated that the risk of progression to AIDS or death for patients on HAART in the Swiss Cohort was 14% of patients not on HAART.
Based on excellent results for patients who started HAART with very low CD4 and high viral load counts, The authors concluded "[HAART] can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV."
This study compared patients on HAART and not on HAART in Cape Town, South Africa. It found that "HAART was associated with decreased AIDS [adjusted rate ratio [ARR], 0.16; 95% confidence interval (CI), 0.08-0.31) and death (ARR, 0.10; 95% CI, 0.06-0.18)."
This study of over 9,000 patients in Europe, Argentina and Israel showed the decline in deaths and AIDS as a result of the introduction of HAART. The authors conclude "The initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS."
This list of clinical trials demonstrating the efficacy of specific
antiretrovirals is incomplete. Currently, we neither list all the
available antiretrovirals nor, in some cases, all the phase III trials
for a particular antiretroviral. We hope to make this list more
complete with time.
This trial is described as follows by NIAID: "A clinical trial known as BW 002 compared AZT with placebo in 282 patients with AIDS or advanced signs or symptoms of HIV disease. In this study, which led to the approval of AZT by the FDA, only one of 145 patients treated with AZT died compared with 19 of 137 placebo recipients in a six month period. Opportunistic infections occurred in 24 AZT recipients and 45 placebo recipients. In addition to reducing mortality, AZT was shown to have reduced the frequency and severity of AIDS-associated opportunistic infections, improved body weight, prevented deterioration in Karnofsky performance score, and increased counts of CD4+ T lymphocytes in the peripheral blood (Fischl et al., 1987; Richman et al., 1987). Continued follow-up in 229 of these patients showed that the survival benefit of AZT extended to at least 21 months after the initiation of therapy; survival in the original treatment group was 57.6 percent at that time, whereas survival among members of the original placebo group was 51.5 percent at nine months (Richman and Andrews, 1988; Fischl et al., 1989)."
This study is described as follows by NIAID: "In another placebo-controlled study known as ACTG 016, which enrolled 711 symptomatic HIV-infected patients with CD4+ T cell counts between 200 and 500 cells/mm3, those taking AZT were less likely to experience disease progression than those on placebo during a median study period of 11 months (Fischl et al., 1990). In this study, no difference in disease progression was noted among participants who began the trial with CD4+ T cell counts greater than 500/mm3."
Concorde was the biggest AZT monotherapy study over the longest period of time. But it showed unequivocally that AZT is not the cause of AIDS. Concorde only examined people with HIV WITHOUT symptoms of AIDS. It compared two strategies: Approximately half the trial participants took AZT immediately and the other half took placebo UNTIL they developed AIDS. Once patients progressed to AIDS, they were unblinded from the trial and given AZT. The participants taking AZT immediately had slower disease progression in the first year, but this dissipated with time resulting in no statistical difference in progression to AIDS. Since a large, approximately equal, number of participants in both arms progressed to AIDS, it clearly shows that AZT was no more harmful than placebo and therefore cannot be the cause of AIDS.
The denialists misrepresent the following about the Concorde trial: In a long-term follow up of the Concorde patients those who deferred AZT treatment until they got AIDS were less likely (slightly, but statistically significantly) to die than those who took it immediately. But at this point the researchers were no longer comparing placebo against AZT.
As a scientist involved in the Concorde trial explained in an affidavit rebutting AIDS denialist Anthony Brink in a South African court case which Brink pulled out of, Concorde was not testing whether AZT was better than placebo; this was already known. It was only trying to determine whether AZT should be taken before one developed AIDS symptoms. It concluded that one should not.
If the patients in the placebo arm stayed on placebo and never took AZT when they got AIDS, then a comparison would have been possible (and we can conclude from the trials described above that such hypothetical patients would have done very badly). But this is not what happened: patients on placebo indeed started AZT treatment when they developed AIDS because AZT had previously been shown unequivocally to be beneficial for people with AIDS.
Also, if the patients who took AZT immediately progressed to AIDS faster than the placebo group then one could conclude that AZT in patients without AIDS symptoms is dangerous. But the study show the opposite result, albeit with reduced benefit over time.
We now know why taking AZT as a monotherapy before developing symptoms of AIDS was an unsuccessful strategy. Patients taking one antiretroviral develop a strain of HIV resistant to the virus in very short time (a few months on average). Consequently the drug stops destroying HIV and patients then experience the side-effects without the benefits. Then when they do eventually get AIDS, the drug no longer has a useful effect. With today's standard of triple-drug therapy, resistance takes, on average, a few years to develop, but resistance is probably not inevitable. When resistance happens, patients have to switch to a new antiretroviral regimen. The current medical consensus is that treatment should still be deferred until a CD4 count of between 200 and 350 or an AIDS-defining illness occurs.
It should also be noted that when AZT was originally prescribed as a monotherapy, it was prescribed in very high doses (1500mg per day). Nowadays it is prescribed in much lower doses (usually 500mg per day).
This trial showed that adding lamivudine to AZT containing regimens slowed HIV progression and improved survival.
We include this study to debunk a denialist lie that didanosine was registered by the US Food and Drug Administration (FDA) without a clinical trial being conducted. The FDA registered didanosine before this trial was published but the regulator had access to the trial data and results when registration took place.
Clinical trials demonstrating the efficacy of nevirapine in reducing HIV viral load and increasing CD4 counts are described in the drug's FDA package insert.