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NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASE (NIAID)

http://www.niaid.nih.gov

 

FOR IMMEDIATE RELEASE
Monday, June 8, 2009
 
Media Contact: Laura Sivitz
(301) 402-1663
sivitzl@niaid.nih.gov
 
 

 
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 counts­a measure of immune health­between 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 sponsor­the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health­end 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.
 
The study investigators say this new finding has the potential to change the standard of care for HIV infection in dozens of countries around the world where ART is initiated only when CD4+ T cell counts drop below 200 cells/mm3. Like the results of several recent epidemiologic studies in developed countries that examined the optimal time to begin ART, the new finding underscores the importance of identifying people who are HIV-infected earlier in the course of their infection and starting ART earlier.
 
“The public health community now has evidence from a randomized, controlled clinical trial­the gold standard­that starting ART at CD4+ T cell counts between 200 and 350 cells/mm3 in resource-limited settings yields better health outcomes than deferring treatment until CD4+ T cell counts drop below 200 cells/mm3,” says NIAID Director Anthony S. Fauci, M.D.
 
“The number of people who meet the medical criteria for receiving ART likely will grow as treatment guidelines are revised as a consequence of this finding, challenging the global community to supply antiretroviral drugs to all who need them,” adds Carl Dieffenbach, Ph.D., director of the NIAID Division of AIDS. “Today, only 30 percent of HIV-infected individuals in low- and middle-income countries who need ART are receiving it.”
 
The clinical trial CIPRA HT 001 began in 2005. It is funded by NIAID through the Comprehensive International Program of Research on AIDS (CIPRA) and is being carried out by the Haitian Group for the Study of Kaposi’s Sarcoma and Immune Deficiency Disorders (GHESKIO) Centers in Port-au-Prince, Haiti. The principal investigator is Jean William Pape, M.D., the director of the GHESKIO Centers and a professor of medicine at Weill Medical College of Cornell University.
 
The trial enrolled 816 HIV-infected adults ages 18 and older with early HIV disease and CD4+ T cell counts between 200 and 350 cells/mm3. Half of the participants were assigned at random to begin ART within two weeks of enrollment, and the other half were assigned to defer treatment until their CD4+ T cell counts dropped below 200 cells/mm3 or they were diagnosed with AIDS. This deferred treatment is in keeping with the standard of care in Haiti and the current guidelines of the World Health Organization (WHO). The first-line treatment regimen consisted of the anti-HIV drugs zidovudine, lamivudine and efavirenz.
 
At the time of the DSMB interim review, six participants in the early treatment group had died, while 23 participants in the standard-of-care group had died­nearly four times as many. The DSMB also found that, among participants who began the study without tuberculosis (TB) infection, 18 people in the early treatment group had developed TB, while 36 people­twice as many­in the standard-of-care group had developed TB. These results were statistically significant.
 
In light of these results, the DSMB recommended that NIAID end the trial immediately and that the study team offer ART to all participants in the standard-of-care group who have fewer than 350 CD4+ T cells/mm3. The DSMB also recommended that the study team continue to follow all participants for another year and make every effort to ensure that participants receiving ART continue their therapy. NIAID concurred with these recommendations.
 
The study investigators are notifying all participants and have notified institutional review boards and national ethics committees involved with CIPRA HT 001 as well as the Haitian Ministry of Health about the findings of the DSMB. Investigators also have shared the information with WHO, the U.S. President’s Emergency Plan for AIDS Relief, and the Global Fund to Fight AIDS, Tuberculosis and Malaria.
 
For more information about CIPRA HT 001, see Questions and Answers: The CIPRA HT 001 Clinical Trial.
 

For more information about HIV/AIDS prevention, treatment and research, go to www.aids.gov.

NIAID conducts and supports research­at NIH, throughout the United States, and worldwide­to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov. 
 
The National Institutes of Health (NIH)­The Nation's Medical Research Agency­includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
 
 

 
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IAPACrec JIAPAC 2009.pdf

 

Reseracher Science 2009.pdf

HIV Child Science 2009.pdf

AIDS case reporting: do we still need it?

John M Kaldor, Valerie Delpech, Rebecca J Guy

The world cares about HIV because it causes AIDS, a disease which is fatal in the absence of treatment. The leading international HIV journal is AIDS, and the megaevent that brings people together every 2 years to review and boost the worldwide response to the HIV pandemic is known as the International AIDS Conference. It may therefore seem appropriate that, more than 25 years into the pandemic, public-health agencies in almost every country continue to document, analyse, and publish the occurrence of AIDS.1,2 In fact, for most people with HIV infection who receive eff ective treatment, development of AIDS is now a rather infrequent and generally reversible event. Policy makers in many countries do not make use of AIDS case counts anymore, but now focus on new HIV diagnoses as their basic surveillance indicator. In resource-restricted settings, AIDS case reports have long been regarded as so under-reported that they do not have any value,3 and repeat prevalence surveys have been adopted to monitor the HIV epidemic.4 The defi nition of AIDS is not even internationally consistent; in the USA, AIDS cases are defi ned on the basis of typical illnesses or a CD4-positive cell count under 200 per μL,5 whereas in Europe6 and Australia7 the defi nition relies only on the illnesses. Resource-restricted countries can record AIDS cases on clinical criteria without the requirement of an HIV positive test, or can use a defi nition that is based on a
symptom score if HIV testing is available.8 In these circumstances, AIDS case reporting may be
placing an unnecessary burden on clinicians and stretching the scarce resources of health departments for little purpose. We review the reasons why AIDS case reporting was introduced in the fi rst place, examine whether it should continue to be used in the routine
surveillance of HIV infection and, if so, consider ways to improve its interpretability. History enables us to distinguish three distinct eras in AIDS reporting. In the beginning, back in 1981, there was only AIDS. Its defi nition as a cluster of characteristic infections and malignant diseases was established with the fi rst cases identifi ed.9 During the next 3 years, reporting
AIDS cases was the only way that health authorities could track this new and frightening epidemic. Although an infectious cause was postulated, no evidence existed for a specifi c agent. It is impressive that the primary modes of HIV transmission, and hence the key prevention strategies, were identifi ed on the basis of epidemiological linkages discovered through investigations of very small numbers of AIDS cases.9 The second era of AIDS reporting began with the introduction of tests for HIV antibody in 1984. The discovery that the presence of HIV antibodies was synonymous with active HIV infection10 opened up new possibilities for population monitoring. With this powerful diagnostic test, HIV reporting might have quickly replaced AIDS reporting, but there were several counterarguments. First, there was a real concern about the potential for discrimination.11 Although public-health procedures and regulations were implemented to protect the privacy of HIV-related records, there were also voices calling for mandatory testing and coercive measures for those found positive. In this environment, there was strong opposition to the use of any information about an HIV diagnosis beyond an individual’s clinical needs, coupled with a concern that reporting of HIV diagnoses might discourage people from seeking testing.12 AIDS case reporting was seen as a somewhat diff erent matter, because it was already in place, and perhaps also because
there was seen to be a greater legitimacy for authorities to obtain statistical information about people with a serious illness and frequent contact with health services, whose survival was likely to be short. Epidemiological principles provided an additional rationale for AIDS case reporting. Access to HIV testing was expanding but still patchy, so the description of the epidemic derived from analyses of new diagnoses of HIV would be highly biased because of its dependence on testing access and uptake. In contrast, people with AIDS would inevitably need to access the health system; therefore, AIDS could be recorded and analysed in a way
that mirrored the true population pattern of its occurrence. AIDS cases were only the tip of the iceberg that was the HIV epidemic. However, at least we knew we were only looking at the tip, whereas with HIV case reporting we could not know which part of the iceberg we were viewing. AIDS case reporting was also regarded as the preferable international standard because many countries of the developing world that had no access to HIV testing could use the syndromic AIDS case defi nition for surveillance.8 Counts of AIDS cases could show the presence of the HIV epidemic in these countries, and hence at least had advocacy value.Even though some countries adopted HIV case reporting at the end of the 1980s, all countries continued to report AIDS cases.1,13,14 WHO established procedures that provided the basis for inter-country comparisons and tracking time trends, understanding that the under-reported AIDS counts from resource-restricted settings could not be compared with those from resource-rich countries.3,15 In countries with good reporting practices, AIDS case counts
became important as the raw material for historical reconstruction of the HIV epidemic,16,17 through the method of mathematical back-projection.18 The third era of AIDS case reporting began in 1996, with the introduction of combination antiretroviral treatment.

Soon after, AIDS case counts fell dramatically1,2,19 in countries where these treatments were accessible. Whereas AIDS had once meant that a person was in the late stages of HIV infection with a high probability of dying within 1–2 years, the improved treatment options
could postpone AIDS occurrence indefi nitely, or provide a substantial amelioration of immunological function in people diagnosed with advanced disease. AIDS no longer signifi ed an irreversible stage in the progression of HIV. Illnesses that qualifi ed as AIDS still arose in people on antiretroviral drugs, but they indicated poor adherence to treatment or development of resistance rather than the underlying iceberg of HIV infections in the wider population. The new treatments had such a great eff ect on slowing the time to development of AIDS that they eff ectively rendered back-projection obsolete. When combination antiretroviral treatment fi rst
appeared, it was assumed to be too expensive for resourcerestricted countries, even though they had the highest number of people with HIV infection. This assumptionwas widely challenged and was overturned by the establishment of major bilateral and multilateral funding
programmes for HIV treatments.20,21 As the availability of treatment has expanded, many developing countries have also greatly increased their ability to diagnose HIV infection, both for individual clinical purposes22 and for epidemiological surveillance. Despite all these changes, AIDS case reporting still exists as a formal surveillance mechanism separate from whatever systems may now be used for HIV case reporting, almost everywhere in the world.
It is now apparent that AIDS case reporting has never been a valid international standard for monitoring the HIV epidemic, because of the variable, high, and unquantifi able under-reporting in many developing countries. With established HIV case reporting systems in most industrialised countries and the treatment revolution having entirely changed the epidemiological meaning of AIDS, should doctors still be required to report the first AIDS clinical event in their patients to public-health authorities? In resource-rich countries, where most people have access to eff ective treatment, the answer is clear: there is now little reason to maintain the separate and systematic recording of all AIDS events, many of which happen after many years of treatment. The illness that we call AIDS is no longer a defi ni tive marker of irreversible disease progression, and most people who develop it fully recover if treated appropriately. Resource-rich countries can now focus on their HIV case reporting systems, and
ensure that these systems comprehensively describe the demographic, behavioural, and clinical characteristics of people who are diagnosed with the infection. The main rationale for keeping systems for reporting AIDS cases may be related to those resource-rich countries in which HIV case reporting is not well established. Many large European countries—notably, Italy and Spain—still do not have national reporting of HIV diagnoses.1 In the USA, some key states have taken some time to adopt HIV reporting, despite its national endorsement.23 The decision to eliminate the separate reporting of AIDS by prespecified dates may in fact provide a strong incentive to accelerate the implementation of HIV case reporting. From a public-health perspective, AIDS in resource-rich countries is now of interest only if it arises in people who
have never previously been diagnosed with HIV infection. Such AIDS cases are a subset of new HIV diagnoses and, similar to low CD4-positive cell counts at HIV diagnosis, indicate the presence of late presenters—ie, subpopulations with poor access to testing and a corresponding need to improve relevant services. The present AIDS surveillance systems in many resource-rich countries are not yet able to monitor this need, because they do not routinely distinguish cases detected at the time of HIV diagnosis from those that develop at a later stage. However, resource-rich countries with HIV case reporting systems should in fact have no diffi culty in defi ning the clinical stage of newly reported cases, either by linking clinical
and laboratory records, or by seeking information directly from doctors responsible for reporting new HIV diagnoses. In Australia, UK, and parts of Europe, cases of HIV presenting with one or more AIDS-defi ning illness are now more than half the reported diagnoses of AIDS, and their number has remained steady for several years.2,24,25 AIDS-related illness that develops some time after HIV diagnosis is mainly of clinical rather than public-health
importance, indicating poor adherence to treatment or development of resistance to antiretroviral drugs. AIDS case reporting was used in the past to describe the spectrum of illnesses arising in people with HIV infection, and diff erences in this spectrum across population groups and over time. However, it has always provided an incomplete picture because it captures only the first AIDS-related events in individuals. Clinical cohort studies
and obser vational databases have, to a large extent, taken over the task of defi ning the spectrum of HIV-related illnesses,26 and are also increasingly used in developing countries to investigate treatment uptake and outcome.3 Cohorts are also suited to monitoring the occurrence of AIDS in people who have not received treatment despite an earlier HIV diagnosis, an indicator of barriers, or inadequate access to medical services. For resource-restricted settings, further discussion about the role of AIDS case reporting systems might be needed. There are a few countries that still rely on AIDS case counts as their core surveillance system for monitoring HIV epidemic, and publish regular analyses of these counts in their public-health bulletins. Such counts might be misleading because of a combination of under-reporting, under-diag nosis, and probably some over-diagnosis. Nevertheless, they have an undoubted advocacy role in the absence of other forms of systematic surveillance. Although many developing coun tries no longer routinely publish AIDS case counts, most still have procedures for reporting AIDS cases and do not have systems for routine HIV case reporting. Even developing countries that make extensive use of HIV prevalence surveys may be cautious
about abandoning AIDS case reporting in the absence of systematic proced ures for HIV case reporting. Public-health case reporting in resource-rich countries should now focus on new diagnoses of HIV infection, including monitoring and analysis of clinical and immunological status at fi rst HIV diagnosis. In these countries, there is no longer a place for separate AIDS
reporting systems that do not distinguish between cases detected at fi rst HIV diagnosis and those that arise after years of treatment. For resource-restricted settings, consideration of the role of AIDS case reporting may not be an immediate priority, but could form part of the ongoing, widespread discussion about the future direction of national surveillance systems for tracking the HIV epidemic and its related risk factors.

If there is to be a substantial change to the way we report on AIDS cases, countries should consider the associated logistical issues and respond in a systematic way. Removing AIDS from the list of notifi able diseases may be seen as sending the wrong message to senior policy makers and politicians, and reduce the profi le of HIV as an important public-health issue. The world does not want to give the impression, even inadvertently, that it no loger cares about
AIDS cases; rather, the change in focus should indicate that the wellbeing of people with HIV infection is of paramount importance. Although there will always be some diversity among countries in their HIV surveillance systems, any action that changes reporting procedures or reaches a consensus about how to present data derived from surveillance systems will ideally be taken on an international basis, after appropriate consultation and negotiation. Conflict of interest statement We declare that we have no confl ict of interest. Acknowledgments This manuscript arose from a presentation made at the 2006 meeting of the Annecy group, which was held in Berlin, Germany. The National Centre in HIV Epidemiology and Clinical Research is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, University of New South Wales, NSW, Australia.

References

1 EuroHIV. European Centre for the Epidemiological Monitoring of
HIV/AIDSWHO and UNAIDS Collaborating Centre on HIV/AIDS.
HIV/AIDS Surveillance in Europe, Mid-year report 2006 No 74.
Saint-Maurice: French Institute for Public Health Surveillance, 2007.
2 National Centre in HIV Epidemiology and Clinical Research.
HIV/AIDS, viral hepatitis and sexually transmissible infections in
Australia. Annual Surveillance Report 2006: National Centre in HIV
Epidemiology and Clinical Research, The University Of New South
Wales, 2006. http://www.nchecr.unsw.edu.au/NCHECRweb.nsf/
page/Annual%20Surveillance%20Reports (accessed July 22, 2008).
3 Diaz T, Loth G, Whitworth J, Sutherland D. Surveillance methods to
monitor the impact of HIV therapy programmes in
resource-constrained countries. AIDS 2005; 19 (suppl 2): S31–37.
4 WHO Regional Offi ce for Africa. HIV/AIDS Epidemiological
Surveillance Report for the WHO African Region 2005 Update.
http://www.who.int/hiv/pub/epidemiology/afroreport/en/index.
html (accessed May 1, 2008).
5 Centers from Disease Control and Prevention. 1993 revised
classifi cation system for HIV infection and expanded surveillance
case defi nition for AIDS among adolescents and adults.
MMWR Recomm Rep 1992; 41: 1–19.
6 Ancelle-Park RA, Alix J, Downs AM, Brunet JB. Impact of 1993
revision of adult/adolescent AIDS surveillance case-defi nition for
Europe. National Coordinators for AIDS Surveillance in
38 European countries. Lancet 1995; 345: 789–90.
7 Australian Government Department of Health and Ageing.
Communicable Diseases Network Australia. Australian National
Notifi able Diseases Case Defi nitions. 2004. http://www.health.gov.
au/internet/wcms/publishing.nsf/Content/cda_
surveil-nndss-dislist.htm (accessed 27 June, 2006).
8 World Health Organization. WHO case defi nitions for AIDS
surveillance in adults and adolescents. Wkly Epidemiol Rec 1994;
69: 273–80.
9 Centers for Disease Control and Prevention. Current Trends Update
on Acquired Immune Defi ciency Syndrome (AIDS)—United States.
MMWR Weekly 1982; 31: 507–14.
10 Curran JW, Lawrence DN, Jaff e H, et al. Acquired
immunodefi ciency syndrome (AIDS) associated with transfusions.
N Engl J Med 1984; 310: 69–75.
11 Kegeles SM, Catania JA, Coates TJ, Pollack LM, Lo B. Many people
who seek anonymous HIV-antibody testing would avoid it under
other circumstances. AIDS 1990: 4: 585–88.
12 Forbes A. Mandatory name-based reporting: impact and
alternatives. AIDS Policy Law 1996: 1–4.
13 Monitoring the AIDS Pandemic Network (MAP). AIDS in Asia: face
the facts—a comprehensive analysis of the AIDS epidemics in Asia.
Geneva: Monitoring the AIDS Pandemic Network, 2004. http://
www.fhi.org/en/hivaids/pub/survreports/aids_in_asia.htm
(accessed July 22, 2008).
14 Sladden T. Twenty years of HIV surveillance in the Pacifi c—what do
the data tell us and what do we still need to know?
Pacifi c Health Dialog 2005; 12: 23–37.
15 World Health Organization. Global AIDS surveillance—part I.
Wkly Epidemiol Rec 1997; 72: 357–58.
16 Centers for Disease Control and Prevention. HIV Prevalence
Estimates and AIDS Case Projections for the United States: Report
Based upon a Workshop—Appendix A. MMWR Wkly 1990;
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17 The incidence and prevalence of AIDS and prevalence of other severe
HIV disease in England and Wales for 1995 to 1999: projections using
data to the end of 1994. Commun Dis Rep CDR Rev 1996; 6: R1–21.
18 Brookmeyer R, Damiano A. Statistical methods for short-term
projections of AIDS incidence. Stat Med 1989; 8: 23–34.
19 The UK Collaborative Group for HIV and STI Surveillance. Testing
Times — HIV and other Sexually Transmitted Infections in the
United Kingdom: 2007. London: Health Protection Agency, Centre for
Infections, 2007. http://www.hpa.org.uk/web/HPAweb&HPA
webStandard/HPAweb_C/1203084355941 (accessed July 22, 2008).
20 World Health Organization. Progress on Global Access to HIV
Antiretroviral treatment: An Update on “3 by 5”. Geneva:
WHO, 2006. http://www.who.int/hiv/fullreport_en_highres.pdf
(accessed July 22, 2008).
21 The United States President’s Emergency Plan for AIDS Relief.
Bringing Hope: Supplying Antiretroviral Drugs for HIV/AIDS
Treatment. Washington, DC: Offi ce of the US Global AIDS
Coordinator, 2006. http://www.state.gov/documents/
organization/66513.pdf (accessed July 22, 2008).
22 World Health Organization. Guidance on provider-initiated HIV
testing and counselling in health facilities. Geneva: WHO, 2007.
23 Centers for Disease Control and Prevention. HIV/AIDS
Surveillance Report, 2005. Vol 17. Rev ed Atlanta: Department of
Health and Human Services, Centers for Disease Control and
Prevention, 2007. http://www.cdc.gov/hiv/topics/surveillance/
resources/reports/2005report/ (accessed July 22, 2008).
24 Brannstrom J, Akerlund B, Arneborn M, Blaxhult A, Giesecke J.
Patients unaware of their HIV infection until AIDS diagnosis in
Sweden 1996–2002—a remaining problem in the highly active
antiretroviral therapy era. Int J STD AIDS 2005; 16: 702–06.
25 McDonald AM, Li Y, Dore GJ, Ree H, Kaldor JM. Late HIV
presentation among AIDS cases in Australia, 1992–2001.
Aust N Z J Public Health 2003; 27: 608–13.
26 Law M, Friis-Moller N, Weber R, et al. Modelling the 3-year risk of
myocardial infarction among participants in the Data Collection on
Adverse Events of Anti-HIV Drugs (DAD) study. HIV Med 2003;
4: 1–10.

 

Two Large Cohort Studies Do Not Resolve Question of When to Start Antiretroviral Treatment

By Liz Highleyman

Over the years of the HIV/AIDS epidemic, expert opinion about the best time to start antiretroviral therapy (ART) has gone in cycles, from the "hit early, hit hard" mantra of the late 1990s to delaying as long as possible to avoid worrisome drug side effects.

In the past few years, a growing body of evidence has indicates that earlier treatment -- before the CD4 cell count falls to the current treatment guidelines threshold of 350 cells/mm3 -- may have substantial benefits. Much of this evidence suggests that long-term HIV infection, and especially ongoing viral replication, have previously unappreciated deleterious effects throughout the body, even before the immune system sustains extensive damage.

Two studies presented this week at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) in Montreal looked at associations between time of treatment initiation and survival -- but they did not come to the same conclusion.

NA-ACCORD

In the first presentation, Mari Kitahata described findings from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), which is collecting data from HIV positive patients from multiple cohorts in the U.S. and Canada.

At the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008) this past fall, Kitahata reported that people who started combination ART with a CD4 count of 350 to 500 cells/mm3 had a 71% lower risk of death compared with patients who deferred therapy (including some who started right below 350 cells/mm3, some who waited longer, and some who died without ever receiving treatment).

At this week's meeting, she presented a further analysis comparing mortality among 2620 individuals who initiated treatment with more than 500 cells/mm3 versus patients who started in the 350-500 cells/mm3 range. This analysis only included people who had a CD4 count above 500 cells/mm3 at the time of HIV diagnosis, and it not consider patients who started treatment below 350 cells/mm3.

Results

The proportion of patients who started treatment above 500 cells/mm3 peaked at 16% in 1997-1998 (the height of the "hit early, hit hard" era), and fell to 10% by 2003.

The early treatment group initiated therapy with median CD4 count of 674 cells/mm3, compared with 435 cells/mm3 for those who deferred treatment.

196 patients died in the early treatment group compared with 271 in the deferred group, a statistically significant difference (P < 0.001).

After controlling for potential confounding factors, the risk of death was 60% higher in the deferred group compared with the early treatment group (relative hazard [RH] 1.6).

Older age was also a predictor of death, but baseline HIV viral load was not.

Among patients with more than 500 cells/mm3, the risk of death did not decrease linearly with rising CD4 counts.

Among the patients who deferred therapy, about 10% died within 6 years of follow-up, and about 15% within 8 years.

These findings, the researchers concluded, "support the initiation of HAART earlier in the course of HIV disease than currently recommended."

ART Cohort Collaboration

The second analysis, presented by Jonathan Sterne of the When To Start Consortium, was much larger, including data from more than 21,000 HIV patients in several North American and European cohorts participating in the ART Cohort Collaboration.

Patients in this analysis started treatment for the first time with a CD4 count below 550 cells/mm3. At study entry, none had a diagnosis of AIDS and none were current or former injection drug users (a group with an elevated risk of death due to non-disease-related causes such as overdose and violence). Since most HIV positive people in industrialized countries no longer start treatment with very low CD4 counts, the researchers also looked at historical data from the pre-HAART era.

The researchers compared the effect of deferred versus early therapy on rates of progression to AIDS or death, as well as death alone, in adjacent 100 cells/mm3 CD4 count strata.

Results

Patients who deferred treatment until they reached the 251-350 cells/mm3 range had a 28% higher rate of AIDS or death compared with those who started with 351-450 cells/mm3 (hazard ratio [HR] 1.28)

Not surprisingly, the deleterious effect of deferring therapy was greatest at the lower CD4 count strata.

Starting treatment earlier had a decreasing benefit at the higher CD4 count strata.

Once the CD4 count reached approximately 400 cells/mm3, earlier treatment conferred no significant additional benefit (HRs close to 1).

"In the absence of evidence from a randomized controlled trial (the only design that can exclude the influence of unmeasured confounding)," the researchers concluded, "these findings should help guide physicians and patients balancing treatment benefits and toxicities in deciding when to initiate ART."

Such a trial is currently under discussion, but remains controversial due to the enormous cost and logistical difficulties of enrolling a very large number of participants, which would be necessary in order to tease out the small absolute differences in outcomes among relatively healthy individuals with well-preserved immune function.

In a press conference discussing the findings, Kitahata said that future studies need to separate out causes of death -- many past studies have only report all-cause mortality -- given the increasing appreciation of the impact of non-AIDS disease.
Sterne emphasized that while earlier therapy above 350 cells/mm3 may indeed be beneficial, these findings also underline the need to test, diagnose, and get people on treatment when they can benefit most, before they fall below 250-300 cells/mm3.

2/13/09

References

M Kitahata, S Gange, R Moore, and others. Initiating rather than deferring HAART at a CD4+ count > 500 cells/mm3 is associated with improved survival. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 71.

J Sterne and the When to Start Consortium. When should HIV-infected patients initiate ART? Collaborative analysis of HIV cohort studies? 6th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 72LB.

 

HIV Infection Increases the Risk of Atherosclerosis as Much as Traditional Risk Factors

By Liz Highleyman

As people with HIV live longer thanks to effective antiretroviral therapy, cardiovascular disease has become a growing concern. Several studies have shown that HIV positive people are more likely to have various surrogate markers of cardiovascular disease, as well as higher rates of clinical events, but it is not yet clear whether this is due to HIV infection itself, antiretroviral therapy, or some combination of known and unknown factors.

As reported at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) this week in Montreal, Carl Grunfeld and colleagues compared rates of pre-clinical atherosclerosis in HIV positive patients and HIV negative control subjects.

Atherosclerosis, or "hardening of the arteries," can lead to heart attacks and strokes. It is increasingly clear that atherosclerosis involves not only the blockage of arteries by plaque, but also a complex inflammatory process that damages the blood vessel lining.

Pre-clinical atherosclerosis is often assessed by looking at carotid intima-media thickness (IMT), a measure of the health of the carotid arteries that supply the brain. IMT can be measured either in the common carotid artery or in the bulb region where it branches off into the internal carotid artery. Because the bulb is an area of blood turbulence that is more susceptible to arterial damage, changes are easier to detect in the bulb; this method, however, is more difficult than assessing IMT in the internal carotid.

Prior studies have produced conflicting data about the link between HIV infection and atherosclerosis. Five studies that found no association measured IMT in the common carotid only, while two studies that did see a link assessed IMT in both the common carotid and in the internal carotid bulb.

In the present cross-sectional study, the researchers compared carotid IMT, measured in both the common carotid and the internal carotid bulb, in 433 HIV positive patients in the Fat Redistribution and Metabolism in HIV Infection (FRAM) study and 5749 healthy HIV negative control subjects in the Coronary Artery Risk Development In Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA).

At baseline, FRAM participants were younger than those in the general population studies (median 49 vs 60 years) and were more likely to be men (70% vs 47%). In addition, the HIV positive participants were more likely to be current or former smokers and had higher total cholesterol and triglyceride levels, but they had a lower rate of diabetes. More than 90% were taking HAART.

Results

HIV positive patients had greater carotid IMT than HIV negative control subjects, but this was only statistically significant for the internal bulb region:

 

Internal carotid bulb: 1.17mm vs 1.06 mm (difference of 0.11; P < 0.0001);

Common carotid: 0.88mm vs 0.86mm (difference of 0.02; P = 0.017, non-significant).

Focusing on internal carotid bulb IMT, differences between HIV positive and HIV negative participants were larger after adjusting for confounding factors:

 

Adjusted for age, sex, and race/ethnicity: difference of 0.19 (P < 0.0001);
Adjusted for demographics and traditional cardiovascular risk factors: difference of 0.15 (P = 0.0001).

For common carotid IMT, the same pattern was seen, but the magnitude was much less:

 

Adjusted for age, sex, and race/ethnicity: difference of 0.04 (P = 0.0004);
Adjusted for demographics and traditional cardiovascular risk factors: difference of 0.03 (P = 0.005).

In a multivariate analysis, the effect of HIV infection on internal carotid bulb IMT (expressed as difference in mm) was similar to that of major traditional cardiovascular risk factors:

 

HIV infection: 0.15 mm;
Male sex: 0.13 mm;
Current smoking: 0.17 mm;
Diabetes: 0.12 mm;
Older age (per 10 years): 0.16 mm.

The effect of HIV infection was greater than that of elevated blood pressure or blood lipid levels.

The effect of HIV infection on IMT was larger in women than in men, especially when measured in the internal carotid bulb.

Based on these findings, the investigators concluded, "After adjusting for demographics and traditional cardiovascular disease risk factors, HIV infection is accompanied by more extensive atherosclerosis as measured by carotid IMT."

Speaking at a press conference, Grunfeld said that the strong effect of HIV infection itself on cardiovascular disease would likely far outweigh the "small signal" associated with use of specific antiretroviral drugs.

2/13/09

Reference
C Grunfeld, J Delaney, C Wanke, and other. HIV infection is an independent risk factor for atherosclerosis similar in magnitude to traditional cardiovascular disease risk factors. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 146.

 

Knowledge and views of Traditional Healers on STIs and HIV in Tamil Nadu
by Munusamy Raviraaj, Director, Kalanjiyam Trust, Chennai

Practice of unprotected pre marital and extra marital sex among men is growing factor that contributes the increasing prevalence of both STIs and HIV among males and females in India.� In India the National AIDS Control Organization estimates that 6% of population affected by STIs with 40 million new cases per year in the country.� In Tamil Nadu the State AIDS Control Society estimates that there are 2.4 million infected with STIs.

In addition to the poor knowledge there is considerable stigma associated with having STIs. Therefore health seeking for sexually transmitted diseases is very poor and the public health system is largely underutilized for these services.

Yet there is high level of concern among male population about sexual problems, in particular for deficiencies in sexual performance.

A significant number of these men go to traditional healers, who are non allopaths, generally practicing siddha or combinations of alternative / traditional medicines.� These practitioners are most sought as they are more readily accessible, often charge less and promise a definite cure.

Yet we know little about these traditional practitioners, their training and background, their knowledge or their practices for providing treatment.
------------------------------

About Siddha Practice

India has long history of different types of traditional healing / medicines; most commonly: Ayurveda, Siddha and Unani.� These alternative medicines are sought by a segment of population for treatment of common illness such as colds to serious more illnesses such as cancer.

In Tamil Nadu, Siddha is the most common form of traditional medicine practiced.� Siddha means achievements and Siddhars were saintly persons who achieved results in medicine. Siddha uses substances of all possible origins in a way that balances the possible harmful effect of each substance.

Preparations are made out of the parts of the plants and trees such as leaves, bark, stem, root etc,

Keeping the above in mind we conducted a study with the primary objective to develop a qualitative understanding about the practices of traditional healers, understand who they are, their profile, types of health problems treated, extent of treatment of STIs / HIV related problems, knowledge on STIs and HIV, STI / HIV treatment and management practices and their views and beliefs about STIs / HIV.
�
Approach and methods

Traditional healers from Chennai and Kancheepuram district were included in the study.� Initially a few traditional healers practicing in Kancheepuram district, were identified through our local village sources.

Following this, the traditional healer networks were used to identify and recruit more healers in the study. Each healer contacted was asked to suggest another healer practicing in different geographic areas.� Finally healers were randomly selected and approached for participation in the study.  Participation in the study was completely voluntary and hardly any healers refused to participate.
�
A Qualitative questionnaire was developed in English and translated into Tamil.� In-depth interviews were conducted with traditional healers on training and practice profiles, reasons for getting into traditional practice and the types of health problems most commonly treated.� Following discussions on their practices the healers were asked about their knowledge and practice on treating STIs and HIV and in general their views on STIs and HIV.

Findings from the study

Profile of healers: Altogether 28 healers participated in the current study. About 25% of healers were less than 40 years with remainder of them between 40 to over 60 years.  Fifty percent of healers in the study had completed between 5 to 10 years of education. Only 18% of healers had completed 11 to 12 years schooling and 14% who had completed over 12 years of school.

Types of Practice: A vast majority of healers interviewed were practicing only Siddha medicine (71%); others were practicing a combination of Siddha and other types of alternative medicine. �The main reasons for getting into traditional practice were reported to be belief if siddha and natural medicines and lack of faith in allopathy and as it was a family tradition.

In addition a number of the practitioners said that they got into practice as they were inclined to 'heal' and help individuals to improve health and wanted to impress on the value of siddha not only as a treatment form, but way of lifestyle for holistic health to more communities.
�
Training received:

The majority of healers (71%) interviewed reported that they were trained only by a 'guru' or had one or more family members such as father, grand father, uncle etc, who were traditional healers and through whom they had received their training.� Only about 11% of healers reported having had formal training through a recognized training institute / center while 18% reported having no training at all.

Among all healers, only 6 had received training in HIV/ AIDS, primarily 1 to 3 day workshops by TNSACS or APAC, but no further follow up since the first training.
�
Practice Profiles:

Just over half of the traditional healers interviewed were in practice for more than 20 years while 11% were in practice for 11 to 20 years and another 25% for 10 or fewer years.

Volume of patients seen by healers varied ranging from <10 to over 300 in the last six months. Nearly half reported having less than 50 patients and 30% reported having more than 100 patients in previous six months.

In terms of types of health problems seen, male and female sexual health problems ranked as one of the highest with more than 90% of healers reporting treating these.

About 75% of traditional healers reported preparing their own medicines, primarily herbal preparations, using various plant sources available locally.� Some healers reported purchasing materials from large suppliers such as IMPCOPS for making preparations.� In general, duration of treatment for common health problems was reported to be between 48 days to 6 months.

Views and knowledge on STIs

Traditional healers refer to STIs as 'palvinai' noi / disease or problems of genitals.� They also referred to them as 'Vettai' noi / disease, a term used only by siddha practitioners that refers to a range of symptoms that occur in the genitals and are related to 'heat' in the body.
�
Only about 54% of healers were aware of two or more symptoms such as foul smelling white discharge, burning on urination, having genital ulcers and sores, or itching in the genitals.� Yet it is of concern to note that 75% reported having treated for STIs and preparing their own medicines for treatment.

There were considerable misconceptions about STIs among these healers.� A predominant belief among healers was that 'heat' in the body was a primary cause of STIs and compounded further if the person has poor immunity.

Some believed that STI can be transmitted through 'air', improper foods/ diet, lack of genital hygiene or even neglected problems in genitals.� A few healers reported that illicit sex or too much sex could also lead to STIs, without reference to protected or unprotected sex.

Treatment of STIs constituted primarily of 'reducing heat' in body and 'purifying the blood'.� Most of the healers reported treatment duration ranging from 48 days to maximum of 6 months.� Treatment primarily included the use of herbal preparations and sometimes inclusion of small amount of 'metals'. Other than this all healers insisted that restrictions on diet and sexual practices were critical factors for complete cure.

Most leaders believed that STIs could be fully cured in six months.

According to them re-occurrence was only possible if person had unprotected sex with an infected person, if one partner had not been treated, having excessive multiple partners, over 'heat' due to certain types of foods or a lack of hygiene.
�
A number of challenges were reported for treating persons with STIs.� The most common was fear, embarrassment and unwillingness to open up about the symptoms.� It was reported that considerable counseling is required during treatment but yet patients do not return for follow up making it difficult to know if the STI had been cured fully.

A number of healers reported that often patients were continuing to engage in multi-partner sex and from what they knew condom use was virtually non existent.
�
Views and knowledge on HIV

Healers were asked to differentiate between HIV and STI; many healers are unsure if STIs and HIV are the same.� Both STIs and HIV are seen as arising from 'heat' and referred to as 'Vettai' and 'Megam' in the later stages.

Seventy nine percent of healers felt that HIV had been in existence for a long time, essentially an 'old disease' which had been referred to as 'Elumburriki noi' previously as it destroyed the bones at the terminal stages.

Many healers believed that HIV can be cured in the early stages of the disease; while the advanced stage of HIV was referred to at 'Mega vettai'.� Similar to above the prevailing belief was that purification of blood was the only way to cure the affected person.

�
Knowledge on methods of transmission were in general very poor among the healers. Only 11% were aware of at least two ways while the remaining 90% of could not give two correct ways of transmission.

Yet 82% thought that HIV can be cured while14% were unsure.
 There was much ambiguity about HIV diagnosis in Siddha and only two healers agreed that there were no ways to directly diagnose HIV in siddha practice.� A few healers reported that diagnosis was possible by checking pulse, seeing existence of skin patches, extreme weakness and pallor.

Treatment for HIV in siddha was reported to be primarily through use of herbal preparations that purify blood.� Nonetheless none of the healers reported having continued treatment of an HIV infected person.� Here again a main challenge that they faced was difficulty in having patients return for follow up. Only one healer reported having referred a patient to allopath.

Discussion

The findings from the above study are a strong indication that traditional practitioners are an important segment that should not be missed by STI and HIV prevention programs. There are considerable gaps in knowledge and high level of misconceptions and yet in reality these practitioners are treating and advising patients on a regular basis.

At the grass root level in rural areas, there is much indication that traditional practitioners are a most commonly approached / utilized health care providers for both male and female sexual health problems, as compared to allopathic providers.

They are perceived as being able to provide a cure that is not costly and further acceptable.  It needs to be recognized that traditional healers are a important segment and as indicated by this current study providing treatment for sexually transmitted diseases.

The findings presented here necessitate strengthening the gaps in knowledge among healers on STIs and HIV and addressing the existing misconceptions.

Existing HIV / STI prevention programs can work in a more targeted way with traditional healers to further sensitize them and improve their knowledge as well as practices.

Not addressing this important group can certainly be considered a missed opportunity for strengthening STI and HIV preventions programs at the grass root levels.
�
www.kalanjyam.org
�
Munusamy Raviraaj
email: raviraaj@gmail.com

Tackling HIV In India: Evidence-Based Priority Setting And Programming

[A pdF copy of the this article is available from the editor of AIDS
INDIA FORUM]

Today's challenge is to scale up proven interventions to reach the
vast majority of India's vulnerable populations.

by Mariam Claeson and Ashok Alexander

ABSTRACT: In the wake of a downward revision of the number of HIV-
infected people, India is launching an ambitious US$2.5 billion, five-
year HIV plan. Responding to new data on HIV prevalence and risk
behavior, India has earmarked almost 70 percent of the budget for
prevention; one-third focuses on prevention activities for those at
highest risk of HIV, and the remainder addresses HIV testing
expansion and services for pregnant women.

About 20 percent of the total budget is for care and treatment.
Although the size and scope of the proposed HIV response pose
challenges, the world has much to learn from India's data informed
approach to policy and priority setting.

[Health Affairs 27, no. 4 (2008): 1091–1102; 0.1377/hlthaff.27.4.1091]

http://content.healthaffairs.org/cgi/reprint/27/4/1091

Assessment of Self-Reported Sexual Behavior and Condom Use Among Female Sex Workers in India Using a Polling Box Approach: A Preliminary Report.

Articles

Sexually Transmitted Diseases. 35(5):489-494, May 2008.
Hanck, Sarah E. MPH; Blankenship, Kim M. PhD; Irwin, Kevin S. MA; West, Brooke S. MA; Kershaw, Trace PhD

Abstract:

Background: The accuracy of behavioral data related to risk for HIV and other sexually transmitted infections is prone to misreporting because of social desirability effects. Because computer-assisted approaches are not always feasible, a noncomputerized interview method for reducing social desirability effects is needed. The previous performance of alternative methods has been limited to aggregate data or constrained by the simplicity of dichotomous-only responses.

We designed and tested a "polling box" method for case-attributable, multiple-response survey items in a low literacy population.

Methods: A cross-sectional survey was conducted with 812 female sex workers in Andhra Pradesh, India. For a subset of questions embedded in a face-to-face survey questionnaire, every third participant was provided graphical response cards upon which to mark their answer and place in a polling box outside the view of the interviewer. Multiple logistic regression analysis was used to test for response differences to questions about socially undesirable, socially desirable, or sensitivity-neutral behaviors in the 2 interview methods.

Results: Polling box participants demonstrated higher reporting of risky sexual behaviors and lower reporting of condom use, with no conclusive response patterns among sensitivity-neutral items.

Conclusion: Our findings suggest that the polling box approach provides a promising technique for improving the accurate reporting of sensitive behaviors among a low-literacy population in a resource poor setting. Additional research is needed to test logistical adaptations of the polling box approach.

(C) Copyright 2008 American Sexually Transmitted Diseases Association

 

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