New research

The results from the DART trial, reported this week in The Lancet, provide important evidence for HAART programmes in resource-constrained settings. From commentary by Phillips & Oosterhout published alongside the results:

In much of sub-Saharan Africa, the scale-up of use of antiretroviral therapy has been so far achieved without routine laboratory monitoring of drug toxicity and efficacy. Until now, there has not been substantive evidence about the consequences of delivering antiretrovirals without such routine monitoring.

In The Lancet today, the DART Trial Team present the Development of AntiRetroviral Therapy in Africa (DART) trial. In DART at enrolment, all participants started triple-drug antiretroviral therapy and were randomised to clinically driven monitoring versus laboratory plus clinical monitoring for toxicity (haematology and biochemistry) and efficacy (CD4-cell counts). Over 5 years, the proportions who had one or more serious adverse events were almost identical, while there was a somewhat higher proportion in the group on clinically driven monitoring who had disease progression or death (28%, compared with 21% in the other group; hazard ratio 1·31, 95% CI 1·14—1·51). This benefit of laboratory plus clinical monitoring is probably due to the use of CD4 count rather than presence of clinical symptoms alone to decide on when to switch to a second-line regimen. This criterion for switching on the basis of CD4 count is just one of the CD4-count switch criteria recommended by WHO; the other criteria (on the basis of CD4-count change from baseline and from peak) are problematic to implement without a baseline CD4 count and frequent CD4 counts being available thereafter.

The other particularly striking result from DART is the 5-year survival in both groups: 87% for clinical monitoring and 90% for laboratory plus clinical monitoring. Such rates of survival are for people in whom the initial median CD4-cell count was 86 cells per μL. For comparison, the survival in the Entebbe cohort of untreated HIV-positive people in 5 years was below 10% (data presented in the DART report), which emphasises the huge clinical benefits of antiretroviral therapy. The DART Trial Team concluded from their results that antiretroviral therapy can be delivered safely with good-quality clinical care, which would allow treatment delivery to be decentralised, and that there is a role for CD4 testing from the second year on antiretrovirals to guide the switch to second-line therapy, which should encourage accelerated development of simpler and cheaper point-of-care CD4 tests. The DART investigators should be complimented for exceptional achievement by completing this important trial with such a low loss to follow-up (7%) in challenging circumstances, which shows that excellent trials can be done in Africa.

The results from DART are very important for antiretroviral programmes, no matter what their current level of routine laboratory monitoring. Programmes that currently deliver antiretrovirals without any laboratory monitoring can be reassured that the vast majority (but not all) of the potential survival benefit of such therapy can be realised with the use of such a simple approach (albeit with particularly intensive and high-quality clinical monitoring, which is a substantial challenge to achieve in routine settings throughout sub-Saharan Africa). Similarly, no antiretroviral programme should enhance laboratory monitoring at the expense of putting more people in need on these drugs. Those clinics that do use routine measurement of biochemistry and haematology can reduce their laboratory costs to enable spending on other aspects of the programme (which has already started in some programmes). Programmes that monitor people on antiretrovirals with CD4 counts should consider adopting the switch criterion used in DART of CD4 count below 100 cells per μL (ie, only this one of the WHO-recommended criteria, rather than all three), and apply this criterion to people who have been on therapy for at least 2 years. Such a delay should help to reduce the number of people in whom a switch is made when viral load is actually suppressed.

Read the commentary at The Lancet (open access; registration required)

Details on the main paper below:

Also see the comment piece Still Crazy After All These Years (open access) by Nicoli Nattrass that appears in the same issue of AIDS & Behavior.

Update (22/01/2010): See AIDS Denialism Under Fire From Researchers by Nora Proops in The AIDS Beacon.

AIDS & Behavior. 2010 Jan 8. [Epub ahead of print]

AIDS Denialism and Public Health Practice

Chigwedere P, Essex M.

In this paper, we respond to AIDS denialist arguments that HIV does not cause AIDS, that antiretroviral drugs are not useful, and that there is no evidence of large-scale deaths from AIDS, and discuss the key implications of the relationship between AIDS denialism and public health practice. We provide a brief history of how the cause of AIDS was investigated, of how HIV fulfills Koch's postulates and Sir Bradford Hill's criteria for causation, and of the inconsistencies in alternatives offered by denialists. We highlight clinical trials as the standard for assessing efficacy of drugs, rather than anecdotal cases or discussions of mechanism of action, and show the unanimous data demonstrating antiretroviral drug efficacy. We then show how statistics on mortality and indices such as crude death rate, life expectancy, child mortality, and population growth are consistent with the high mortality from AIDS, and expose the weakness of statistics from death notification, quoted by denialists. Last we emphasize that when denialism influences public health practice as in South Africa, the consequences are disastrous. We argue for accountability for the loss of hundreds of thousands of lives, the need to reform public health practice to include standards and accountability, and the particular need for honesty and peer review in situations that impact public health policy.

PMID: 20058063

Read the full article on SpringerLink (open access)

J Acquir Immune Defic Syndr. 2010 Jan;53(1):86-94.

Brady MT, Oleske JM, Williams PL, Elgie C, Mofenson LM, Dankner WM, Van Dyke RB; for the Pediatric AIDS Clinical Trials Group219/219C Team.

CONTEXT: Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited.

OBJECTIVES:: To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C.

DESIGN, SETTING, AND PARTICIPANTS:: Multicenter, prospective cohort study designed to evaluate long-term outcomes in HIV-1-exposed and infected US children. There were 3553 HIV-1-infected children enrolled and followed up between April 1993 and December 2006, with primary cause of mortality identified in the 298 observed deaths.

MAIN OUTCOME MEASURES:: Mortality rates per 100 child-years overall and by demographic factors; survival estimates by birth cohort; and hazard ratios for mortality by various demographic, health, and antiretroviral treatment factors were determined.

RESULTS:: Among 3553 HIV-1-infected children followed up for a median of 5.3 years, 298 deaths occurred. Death rates significantly decreased between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained relatively stable through 2006. After adjustment for other covariates, increased risk of death was identified for those with low CD4 and AIDS-defining illness at entry. Decreased risks of mortality were identified for later birth cohorts, and for time-dependent initiation of highly active antiretroviral therapy (hazard ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000. All OI mortality declined during the study period. However, a greater decline was noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths from "End-stage AIDS," sepsis and renal failure increased.

CONCLUSIONS:: Overall death rates declined from 1993 to 2000 but have since stabilized at rates about 30 times higher than for the general US pediatric population. Deaths due to OIs have declined, but non-AIDS-defining infections and multiorgan failure remain major causes of mortality in HIV-1-infected children.

PMID: 20035164.

Read at JAIDS.

Science 11 December 2009: Vol. 326. no. 5959, pp. 1476 - 1477

Dozens of studies have been examining people who fend off HIV despite repeated exposures in an effort to find genetic or immunologic factors that can help guide AIDS vaccine research. But all too often the leads point in contradictory directions, in part because investigators use different assays to probe their samples, and there is little coordination among them. Many labs also use wildly varying criteria to decide who qualifies as HIV-resistant, making it difficult to sort out which study subjects were truly exposed and uninfected, were exposed and have an occult infection, or were never exposed in the first place. At the first-ever meeting on natural immunity to HIV, held from 15 to 17 November, researchers attempted to hammer out these and other issues.

Read the article at Science.

doi: 10.1126/science.326.5959.1476

AIDS. 2010 Jan 2;24(1):123-37.

HIV-CAUSAL Collaboration.

OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication. DESIGN: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication. RESULTS: Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001). CONCLUSION: We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

PMID: 19770621

Mortality Rate Still Higher Than for Children without HIV

The death rates of children with HIV have decreased ninefold since doctors started prescribing cocktails of antiretroviral drugs in the mid-1990s, concludes a large-scale study of the long-term outcomes of children and adolescents with HIV in the United States. In spite of this improvement, however, young people with HIV continue to die at 30 times the rate of youth of similar age who do not have HIV, found researchers from the National Institutes of Health and other institutions.

Earlier studies have shown that adults with HIV are living longer because of improved multi-drug antiretroviral regimens known as highly active antiretroviral therapy (HAART). However, limited information has existed about the effectiveness of HAART in improving the survival of children with HIV. The current analysis, published in the Dec. 15 issue of the Journal of Acquired Immune Deficiency Syndromes, delineates the effects of HAART on the rates and causes of death for HIV-infected children and adolescents.

AIDS. 2010 Jan 2;24(1):139-46.

Yotebieng M, Van Rie A, Moultrie H, Meyers T.

OBJECTIVES: Construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4 percentage (CD4%) in children initiating ART, and to assess the association between lower percentiles and subsequent ART responses. DESIGN: Cohort of 1394 HIV-infected children initiating ART between April 2004 and March 2008, Johannesburg, South Africa METHODS: The generalized additive model for location, scale, and shape was used to construct percentile curves for 6-month gain in weight, height, CD4 cell count, and CD4%. Cox proportional models were used to assess the association between lower percentiles of each distribution and death, virological suppression, and treatment failure between 6 to 36 months post-ART initiation. RESULTS: Lower percentiles for gain in weight, CD4, and CD4% count after 6 months of ART, but not height, were associated with poor subsequent treatment outcomes independent of baseline characteristics, with increasing strength of association as percentiles decreased. Age-specific 6-month post-ART weight gain in our cohort was substantially higher compared with 6-month weight gain in non-HIV-infected American children of the Fels Institute cohort and the attained weight-for-age at 6 months post-ART plotted on WHO weight-for-age growth charts were not associated with subsequent treatment outcomes. CONCLUSION: Gain in CD4% in the first 6 months of ART was the best predictor of poor subsequent ART outcomes. In areas with limited access to CD4%, weight gain post-ART using our newly developed reference distributions for HIV-infected children on ART is a good alternative to CD4%, and clearly superior to the commonly used 'Road-to-Health' weight-for-age charts.

PMID: 19940744

A new study has found poorer adherence to antiretroviral therapy among African-American men with HIV who hold conspiracy beliefs, e.g. that HIV is a man-made virus designed to kill Africans.

JAIDS. 2009 Dec 09.

Conspiracy Beliefs About HIV Are Related to Antiretroviral Treatment Nonadherence Among African American Men With HIV

Bogart, Laura M PhD; Wagner, Glenn PhD; Galvan, Frank H PhD; Banks, Denedria MSW

Background: Medical mistrust is prevalent among African Americans and may influence health care behaviors such as treatment adherence. We examined whether a specific form of medical mistrust-HIV conspiracy beliefs (eg, HIV is genocide against African Americans)-was associated with antiretroviral treatment nonadherence among African American men with HIV.

Methods: On baseline surveys, 214 African American men with HIV reported their agreement with 9 conspiracy beliefs, sociodemographic characteristics, depression symptoms, substance use, disease characteristics, medical mistrust, and health care barriers. Antiretroviral medication adherence was monitored electronically for one month postbaseline among 177 men in the baseline sample.

AIDS. 2010 Jan 2;24(1):123-37.

The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals

The HIV-CAUSAL Collaboration

Abstract

Objective: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.

Design: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication.

AIDSTruth contributor Nicoli Nattrass writes in AIDS and Behavior:

In his new book, Denying AIDS, Seth Kalichman observes that people are surprised by the persistence of AIDS denialists: “Are they still around?”[1, p. 1] he is often asked. And it is a good question. Given the large body of scientific and clinical evidence on HIV disease and treatment (expertly summarized by Chigwedere and Essex in this issue of AIDS and Behavior) it is indeed strange that Peter Duesberg and his followers still claim HIV is harmless and that antiretrovirals cause rather than treat AIDS. While such dissident views were intellectually respectable in the 1980s when HIV science was new, they make little sense today. Thus Joseph Sonnabend, a doctor who treated some of the earliest AIDS cases in New York and was well known for arguing that environmental factors may be more important than a virus in driving AIDS, was quick to change his mind once antiretroviral treatment was shown to act against HIV and transform the health of his patients [2, p. 25]. Peter Duesberg, by contrast, refused to accept the evidence, thereby earning the label ‘denialist’ rather than ‘dissident’ [1, 2].

We endorse this call for mandatory disclosure.

Mandatory Disclosure of Pharmaceutical Industry-Funded Events for Health Professionals

Robertson J, Moynihan R, Walkom E, Bero L, Henry D (2009) PLoS Med 6(11): e1000128. doi:10.1371/journal.pmed.1000128

Summary Points

• There are moves internationally to ensure greater disclosure of gifts and educational events for doctors paid for by pharmaceutical manufacturers. However, there is no agreement on appropriate standards of disclosure. In Australia, since mid-2007, there has been mandatory reporting of details of every industry-sponsored event, including the costs of any hospitality provided.
• Examination of the Australian data shows that although expenditure at individual events is often modest, cumulative expenditure is high, particularly in the case of medical specialists prescribing high cost drugs—oncologists, endocrinologists, and cardiologists.
• Although a significant advance, the new Australian reporting standards do not allow assessment of the educational value of sponsored events, and do not include details of speakers or educational content for most events. However, doctors in training are often present at these events.
• At present, the standards of disclosure are inadequate and should not be tied to an arbitrary monetary value of gifts or sponsorship. Reporting standards should require the names of the speakers presenting, whether sponsors played a role in suggestion or selection of speakers or the development of the content of presentations, and the nature of any direct or indirect financial ties between the speakers and the sponsors.
  

Michael Carter writes on aidsmap:

Results of US research “challenge the notion that nevirapine is uniquely associated with hepatotoxicity during pregnancy.” The study did however show that pregnancy itself increased the risk of liver toxicities in women with HIV. The research is published in the November 27th edition of AIDS.

Read more on aidsmap.

AIDS. 2009 Nov 27;23(18):2425-30.

Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure.

Ouyang DW, Shapiro DE, Lu M, Brogly SB, French AL, Leighty RM, Thompson B, Tuomala RE, Hershow RC.

OBJECTIVE: To estimate whether the association between nevirapine (NVP) and hepatotoxicity differs according to pregnancy status in HIV-infected women. METHODS: The present analysis included HIV-infected pregnant women on antiretroviral therapy (ART) from two multicenter, prospective cohorts - the Women and Infants Transmission Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1025 - and HIV-infected nonpregnant women from one multicenter, prospective cohort - the Women's Interagency HIV Study. Using multivariate Cox proportional hazards regression, the interaction between NVP and pregnancy status in terms of hepatotoxicity was investigated. NVP use was dichotomized as use or no use and was further categorized according to ART exposure history. We investigated two outcomes: any liver enzyme elevation (LEE; grade 1-4) and severe LEE (grade 3-4). RESULTS: Data on 2050 HIV-infected women taking ART were included: 1229 (60.0%) pregnant and 821 (40.0%) nonpregnant. Among the pregnant women, 174 (14.2%) developed any LEE and 15 (1.2%) developed severe LEE as compared with 75 (9.1%) and 5 (0.6%), respectively, of the nonpregnant women. In multivariate adjusted models, NVP was not significantly associated with risk of LEE, regardless of pregnancy status; however, pregnancy was associated with an increased risk of any LEE (relative risk 4.7, confidence interval = 3.4-6.5) and severe LEE (relative risk 3.8, confidence interval = 1.3-11.1). The association of pregnancy and LEE was seen, regardless of prior ART and NVP exposure history. CONCLUSION: No significant association between NVP and LEE was observed, regardless of pregnancy status, but pregnancy was significantly associated with increased hepatotoxocity in HIV-infected women.

PMID: 19617813 [PubMed - in process]

What are the causes of AIDS denialism? What are the factors that lead to a loss of public confidence in medical science? Often on aidstruth.org we have focused on debunking the false propaganda of prominent AIDS denialists, but there are other very important causes of people with chronic illnesses choosing to forsake scientifically based medical advice. A crucial one is the often substandard quality of care people receive from their medical practitioners. In the United States, tens of millions of uninsured and under-insured people experience the health system as uncaring and unproviding. In South Africa, where AIDS denialism had its worst effects, a study by Jane Goudge and colleagues at the Centre for Health Policy on the University of Witwatersrand found that "Poor provider-patient interaction led to inadequate understanding of illness, inappropriate treatment action, 'healer shopping', and at times a break down in cooperation, with the patient 'giving up' on the public health system." Healer shopping, or perhaps more appropriately quack shopping, is a consequence of poor health services characterised by disrespectful behaviour from overworked health staff, long waiting lists, queues, and the unavailability of essential medicines and diagnostics.

A number of studies showing a benefit to starting antiretroviral therapy earlier have been reported recently. These have resulted in important changes to guidelines including that infants should be treated immediately upon diagnosis and that adults should be treated as soon as their CD4 counts fall below 350 cells/mm3.

Determining the optimal time to start treatment is one of the most important unanswered questions about antiretroviral treatment. A large open-label treatment trial called START has begun and will likely answer this question within the next few years. It is open to HIV-positive volunteers with CD4 counts > 500 cells/mm3. Volunteers will be randomised to either start treatment immediately or defer treatment until their CD4 counts drop to below 350 cells/mm3 or treatment is clinically indicated.

A few of the studies showing the benefits of earlier treatment than guidelines previously recommended are listed below:

Effect of early versus deferred antiretroviral therapy for HIV on survival

N Engl J Med. 2009 Apr 30;360(18):1897-9.

Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, Hogg RS, Deeks SG, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Goedert JJ, Benson CA, Collier AC, Van Rompaey SE, Crane HM, McKaig RG, Lau B, Freeman AM, Moore RD; NA-ACCORD Investigators.

BACKGROUND: The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS: We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS: In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS: The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy. 2009 Massachusetts Medical Society

PMID: 19339714

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies

Lancet. 2009 Apr 18;373(9672):1314-6. Free full-text article.

When To Start Consortium, Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, Funk MJ, Geskus RB, Gill J, Dabis F, Miró JM, Justice AC, Ledergerber B, Fätkenheuer G, Hogg RS, Monforte AD, Saag M, Smith C, Staszewski S, Egger M, Cole SR.

BACKGROUND: The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies. METHODS: We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for inclusion if they had started combination antiretroviral therapy (while AIDS-free, with a CD4 cell count less than 550 cells per microL, and with no history of injecting drug use) on or after Jan 1, 1998. We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989-95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups. We compared the effect of deferred initiation of combination therapy with immediate initiation on rates of AIDS and death, and on death alone, in adjacent CD4 cell count ranges of width 100 cells per microL. FINDINGS: Data were obtained for 21 247 patients who were followed up during the era before the introduction of combination therapy and 24 444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251-350 cells per microL was associated with higher rates of AIDS and death than starting therapy in the range 351-450 cells per microL (hazard ratio [HR] 1.28, 95% CI 1.04-1.57). The adverse effect of deferring treatment increased with decreasing CD4 cell count threshold. Deferred initiation of combination therapy was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR 1.13, 0.80-1.60, for deferred initiation of treatment at CD4 cell count 251-350 cells per microL compared with initiation at 351-450 cells per microL). INTERPRETATION: Our results suggest that 350 cells per microL should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.

PMID: 19361855

AIDS denialists have claimed that the lack of disease progression in chimpanzees infected with HIV is evidence that the virus is at worst a passenger in human beings and cannot be the cause of AIDS. This was, for example, implied by the journalist Celia Farber in her AIDS denialist piece published in Harper's in 2006.

In the response to Farber, to which several of the AIDSTruth.org team contributed, we wrote:

It is true that HIV replicates inefficiently in chimpanzees, to a much lower level than it does in humans so it usually does not cause disease. However, there are recorded examples of HIV causing immunodeficiency in these animals.

Many agents which cause disease in man are unable to cause disease in a host of other species because they fail to infect, or infect poorly, or produce a different response. HIV has probably been in the chimpanzee population for a very long time. Therefore it is plausible that natural selection has rendered it less harmful.

Former South African President Thabo Mbeki disputed that there was a large AIDS epidemic in South Africa. (1) This was a cornerstone of his promotion of denialist policies. It was echoed by journalist Rian Malan in articles he wrote in Rolling Stone, the Spectator and Noseweek. (2) Mbeki expressed his scepticism when a state institution, the Medical Research Council, released a report titled Adult Mortality in South Africa. It presented unequivocal evidence that HIV was a growing and major cause of death in the country. (3) Mbeki's health minister, Manto Tshabalala-Msimang, tried to suppress the publication of this report. (4)

Over the last decade, the evidence of the country's large AIDS epidemic has accumulated. It is perhaps most succinctly explained with this graph, which demonstrates the unusual and disturbing changing age-pattern of death among adult women in South Africa from 1997 to 2004 , that can only be explained by the AIDS epidemic:

Aidsmap reports:

HIV-positive patients who return to care after being lost to follow-up are five times more likely to die in the short term than patients who remain in HIV care, French investigators report in the online edition of AIDS.

“Increased efforts are needed to reduce loss to follow-up and encourage those patients who no longer attend clinic to return to care,” recommend the authors.

Thanks to effective antiretroviral treatment, the prognosis of many HIV-positive individuals is now near-normal. However, despite the benefits of treatment and care some patients stop attending their HIV clinic.

Read the full article on Aidsmap.

Ndiaye B et al. Characteristics of and outcomes in HIV-infected patients who return to care after loss to follow-up. AIDS 23 (online edition), 2009. doi: 10.1097/QAD.0b013e32832e3469

Korenromp EL, Williams BG, Schmid GP, Dye C (2009) Clinical Prognostic Value of RNA Viral Load and CD4 Cell Counts during Untreated HIV-1 Infection—A Quantitative Review. PLoS ONE 4(6): e5950. doi:10.1371/journal.pone.0005950

The purpose of the study was to determine if the current World Health Organisation criteria for commencing HAART are appropriate. The study abstract concludes:

Findings support the current WHO recommendation (used with clinical criteria) to start antiretroviral treatment in low-income settings at CD4 thresholds of 200–350 cells/µL, without pre-treatment RNA monitoring – while not precluding earlier treatment based on clinical, socio-demographic or public health criteria.

Interestingly, the authors found:

Mean relative risks per 10-fold higher RNA were 2.0 (95% confidence interval (CI): 1.8–2.5) for AIDS (12 studies, 17 datapoints) and 2.5 (2.1–3.0) for death (9 studies, 10 datapoints). These prognostic risks did not vary over time after seroconversion, or with duration of follow-up, geographical region, baseline CD4, use of antiretroviral mono-/bi-therapy, or average clinical progression rates.

They also found:

NIH/National Institute of Allergy and Infectious Disease

Interim review leads to early end of clinical trial in Haiti

A clinical trial has demonstrated that HIV-infected adults in a resource-limited setting are more likely to survive if they start antiretroviral therapy (ART) before their immune systems are severely compromised.

On May 28, 2009, an independent data and safety monitoring board (DSMB) met to conduct a planned interim review of an ongoing clinical study known as CIPRA HT 001, which is being conducted in Haiti. The DSMB found overwhelming evidence that starting ART at CD4+ T cell counts—a measure of immune health—between 200 and 350 cells per cubic millimeter (mm3) improves survival compared with deferring treatment until CD4+ T cells drop below 200 cells/mm3. In light of these results, the DSMB recommended that the trial sponsor—the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health—end the trial immediately, before its scheduled conclusion. NIAID agreed with the DSMB recommendation, and all study participants who have fewer than 350 CD4+ T cells/mm3 will be offered ART.

In what is surely a serious blow to AIDS denialists, researchers have published video microscopy of HIV transferring between T-cells: