|Viral load||Inconsistent surrogate marker||Correlation with health||General|
|The use of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection: Impact on medical, palliative care, and quality of life outcomes|| ||Brechtl et al.
| ||“Improvements in viral load but no corresponding improvements in quality of life”.|
| ||J Pain Symptom Manage. 2001;21:41-51.||2001|
|Inflammatory Reactions in HIV-1-Infected Persons after Initiation of Highly Active Antiretroviral Therapy.|| ||DeSimone JA et al.
| ||“Inflammatory reactions involving opportunistic infections, AIDS-associated malignant conditions, and other noninfectious diseases (mycobacterium avium complex, acute hepatitis, cirrhosis, herpes zoster, Graves disease, autoimmune thyroiditis, systemic lupus erthematosus, lymphoma and Kaposi sarcoma) have recently been described in patients infected with HIV-1. These conditions often appeared shortly after the introduction of HAART and were associated with pronounced reductions in plasma HIV-1 viral load ... [normally considered signs of success of therapy]”|
| ||Ann Int Med. 2000 Sep 19;133(6):447-454.||2000|
|High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.|| ||Piatak M Jr et al.
| ||This study showed that viral load test results do not correlate with illness|
| ||Science. 1993 Mar 19;259:1749-54.||1993|
|Reassessing the goal of antiretroviral therapy in the heavily pre-treated HIV-infected patient.|| ||Deeks SG, Martin JN.
| ||“Even if it can be accepted that an undetectable viral load is an appropriate surrogate marker for clinically relevant outcomes in treatment-inexperienced patients who are initiating combination therapy, it cannot necessarily be accepted without proof that it is a useful surrogate in heavily pre-treated patients...Therefore, until controlled trials are able to prove the utility of an undetectable viral load as a surrogate marker for clinically relevant outcomes in heavily pre-treated patients, we believe that clinicians should show caution before striving for complete viral suppression at any cost”|
| ||AIDS. 2001;15(1):117-9.||2001|
|Detection of human immunodeficiency virus type 1 provirus in mononuclear cells by in situ polymerase chain reaction.|| ||Bagasra O et al.
| ||"...we were able to... show a relation between viral load and the stage of HIV-1 clinical infection. Patients in Stage II [HIV+, but no symptoms] had a significantly lower percentage of HIV-1-positive PBMC than those in Stage III and Stages IV-A to IV-C" [but the authors neglect to mention that this is only true of the average value, there was considerable overlap between individual values. More importantly, they also do not mention that the average value at Stage III (lymph gland enlargement) was higher than at Stage IV-A to C (AIDS) and much higher than at Stage IV-D (Kaposi’s Sarcoma)]. Patients in Stage IV-D (who had Kaposi’s sarcoma only) had relatively low numbers of HIV-1-infected cells.”|
| ||NEJM. 1992;326(21):1385-91.||1992|
|Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: a meta-analysis.|| ||HIV Surrogate Marker Collaborative Group.
| ||Comparisons of studies showing positive effects from lowered viral loads show another inconsistency: dramatic reductions in viral load do not offer any better clinical benefit than small reductions. An analysis of all 16 randomized trials that compared outcomes based on drug-induced lowering of viral load found that drugs that cause marked lowering of viral loads do not show better clinical results than studies with only mild reductions and drugs that cause similar reductions in viral loads have widely varying clinical outcomes. "Short-term changes in these markers (HIV-1 RNA) are imperfect as surrogate end points for long-term clinical outcome because two randomized treatment comparisons may show similar differences between treatments in marker changes but not similar differences in progression to AIDS/death."|
| ||AIDS Res Hum Retroviruses 2000 Aug 10;16(12):1123-33||2000|
|Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy.|| ||Hogg et al.
| ||This study followed 1219 people who were started on "antiretroviral" drugs for the first time. They were followed for 3 years, and mortality was compared among people who started with high and low CD4 counts and high and low "viral loads". They found that the person's initial viral load had no effect on mortality after adjusting for other variables.|
| ||JAMA 286(20); 2568-2577.November 28, 2001||2001|
|Liver Function Tests Independently Predict Survival|| ||Youle Mike
| ||"The role of surrogate markers to predict survival or other outcomes in HIV disease has been an area of interest for many groups, especially as the epidemic has advanced and the range of potential markers has increased. When quantitation of viral load became possible in the mid-1990s, it was widely believed that this would provide the ultimate marker of the risk of HIV progression and death. In fact, this has not proved to be the case, and there has therefore been renewed attention to other, perhaps simpler and cheaper measures of risk. The laboratory measures that are routinely evaluated in HIV-infected patients include hemoglobin levels as a marker of anemia, and liver function tests" [neither anemia nor liver diseases are blamed on hiv]|
| ||Medscape coverage of: XIV International AIDS Conference, 2002||2002|