Related Article(s):

• CDC Urges HIV Tests as Routine in Health Care
• Proposed HIV Testing Guidelines Draw Fire
  

GALVESTON, Texas, Feb. 24 — Only a small fraction of released prisoners with HIV renew their medication prescriptions in time to avoid interruption of treatment, researchers here said.

• Explain to interested patients that interruptions in treatment for HIV have been shown to be associated with poor clinical outcomes.
• Note that this study showed that few inmates released from the Texas prison system while on treatment for HIV renewed their prescriptions in time to avoid a treatment interruption.

In a retrospective cohort study of HIV-positive inmates in the Texas prison system, only 5.4% filled an initial prescription for antiretroviral therapy within 10 days of release, according to Jacques Baillargeon, Ph.D., of the University of Texas Medical Branch, and colleagues.

If that initial prescription is not filled within 10 days, the former inmate will likely have his or her treatment interrupted, at least temporarily, Dr. Baillargeon and colleagues reported in the Feb. 25 issue of the Journal of the American Medical Association.

Indeed, more than 90% of former inmates had a treatment interruption, more than 70% stopped therapy for more than 30 days, and more than 60% interrupted their treatment for more than 60 days, the researchers found.

As a result, many former inmates may do worse than those who adhere to therapy, the researchers said, noting that one major trial has shown that even short treatment interruptions lead to poorer clinical outcomes. (See: HIV Drug Holidays Not a SMART Idea)

Since many inmates also return to high-risk activities, such as drug abuse, treatment interruptions may also create HIV reservoirs and thus risk spread of HIV and perhaps drug-resistant virus, the researchers said.

HIV prevalence in Texas prisons — the country’s largest state system — was consistently 1.5% or higher during the four-year study period, from 2004 through 2007.

Many inmates are treated while in jail, but it’s not known what happens when they are released, Dr. Baillargeon and colleagues said.

To clarify the issue, they looked at medical and prescription records of 2,115 HIV-positive inmates who were on antiretroviral therapy at the time of their release.

The study population is about 55% of the HIV-positive inmates released during the study period, but the rest were not on therapy.

Since most of those who were released do not have private insurance, the researchers tracked their prescriptions through the Texas AIDS Drug Assistance Program (ADAP).

They found that, in addition to the 5.4% who did get their medications within 10 days of release:

• 17.7% did so within 30 days and 30% within 60 days.
• In a multivariate analysis of predictors, Hispanics and African-Americans were less likely to fill a prescription within 10 days (the risk ratio was 0.4 in each case) and within 30 days. (The risk ratio was 0.7 in both cases.)
• Former inmates with an undetectable viral load were more likely to fill a prescription at all time points. (The risk ratios were 1.8 for 10 days, 1.5 for 30 days, and 1.3 for 60 days.)
• Inmates released on parole — compared with those who were unsupervised — were more likely to fill a prescription within 30 and 60 days. (Risk ratios were 1.3 and 1.5, respectively.)
• Former inmates who got help completing a Texas AIDS Drug Assistance Program application — and therefore probably completed it well before their release — were more likely to fill a prescription at all time points. (The risk ratios were 3.1 for 10 days, 1.8 for 30 days, and 1.3 for 60 days.)

The study is limited by the retrospective design, the researchers said, with the possibility that important confounders may have gone unmeasured.

Primary source: Journal of the American Medical Association

Source reference:

Baillargeon J, et al “Accessing antiretroviral therapy following release from prison” JAMA 2009; 301(8): 848-857.S

NEW YORK, March 16 — People whose bodies naturally fight off HIV infections have a team of antibodies that target the virus, researchers here said.

• Explain to interested patients that research on HIV antibodies has focused on finding substances with broadly neutralizing activity against many strains of the virus.
• Note that this study found that people whose bodies naturally fight off HIV have a range of antibodies that target various viral antigens, rather than a single antibody against HIV.

None of the natural antibodies alone is as effective as the four engineered antibodies that have broadly neutralizing effects on HIV, according to Michel Nussenzweig, M.D., Ph.D., of Rockefeller University, and colleagues.

But together — as they appear to act in the bodies of so-called “elite controllers” — they can keep diverse strains of HIV under control, Dr. Nussenzweig and colleagues reported online in Nature.

The finding opens a new avenue of research into antibody-based HIV vaccines, which has been focused so far on trying to find antibodies that block a wide range of different HIV strains.

Such antibodies are known — four have been engineered to target the envelope protein gp140 — but efforts to get patients to produce them have failed.

“We wanted to try something different, so we tried to reproduce what’s in the patient,” Dr. Nussenzweig said in a statement. “And what’s in the patient is many different antibodies that individually have limited neutralizing abilities but together are quite powerful.”

“This should make people think about what an effective vaccine should look like,” he added.

The researchers studied the blood of six patients whose HIV infection is under immune control and found that the B cell memory response to gp140 was composed of up to 50 clones expressing antibodies to the protein.

The gp140 protein — composed of two other proteins, gp120 and gp41 — is essential to HIV’s ability to infect cells. As a result, antibodies to the protein or its subunits have been the target of intensive research.

All told, Dr. Nussenzweig and colleagues found 433 antibodies that bound to the gp140 protein. Of those, 70% bound to the gp120 subunit and 30% to gp41.

Interestingly, the researchers found, none of the gp41 antibodies bound to the regions recognized by two of the broadly-neutralizing engineered antibodies, known as 2F5 and 4E10.

The gp120 protein has been the target of several vaccine candidates, and so the researchers tested their gp120 antibodies for neutralizing activity, compared with immunoglobulins from the patients.

Most of the antibodies showed some degree of neutralizing activity, Dr. Nussenzweig and colleagues found, but never enough to account for all of the patient’s protection.

“We found no case in which a single monoclonal antibody accounts for all of the neutralizing activity in serum,” they said.

Instead, they showed “variable levels of activity against different viruses” and as a group recognized a “broad array” of viral antigens.

“Individually, they’re not as strong as the Famous Four,” Dr. Nussenzweig said, referring to the four engineered gp140 antibodies that have broadly neutralizing activity.

But a vaccine that copied the natural response in these patients might be an effective defender against a range of HIV strains, he said.

Primary source: Nature

Source reference:

Scheid JF, et al “Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals” Nature 2009; DOI: 10.1038/nature07930.

CRÉTEIL, France, March 17 — For HIV patients with suppressed immune systems, adding interleukin-7 to combination therapy increased the number of immune cells, researchers here said.

• Explain to interested patients that although most HIV patients respond to combination antiretroviral therapy with a robust restoration of the immune system, some do not.
• Note that this small study suggests that the cytokine interleukin-7 can cause significant increases in immune cells, although more research is needed.

In a small, open-label phase I/IIa trial, the cytokine was well tolerated and induced a sustained increase in both naive and memory T cells, according to Yves Levy, M.D., of Hôpital Henri Mondor, and colleagues.

The finding is important because a low immune cell count is associated with poorer outcomes, even if the virus itself is well controlled, the researchers reported online in the Journal of Clinical Investigation.

It also comes after two large phase III trials (one led by Dr. Levy) showed that another cytokine, interleukin-2, did not improve outcomes in HIV. (See: CROI: IL-2 Benefit in HIV Ruled Out)

Mounting evidence suggests that the length of time patients spend with a low CD4-positive T cell count is associated with higher morbidity, the researchers said.

“A new frontier in HIV therapy may be defined by the maintenance of a high level of CD4-positive T cells,” they said.

Controlling the virus itself is an “attainable goal,” the researchers said, but although most patients respond to combination antiretroviral therapy with a robust recovery of immune function, some do not.

To test the impact of interleukin-7, the researchers enrolled 14 patients with plasma HIV RNA levels less than 50 copies per milliliter and CD4 cell counts of between 100 and 400 cells per microliter.

Patients were given subcutaneous injections of recombinant human interleukin-7 every second day for 16 days, at one of two doses — six patients got three micrograms per kilogram of body weight, and eight patients got 10 micrograms per kilogram.

All patients in the low-dose group got all eight injections, but one patient in the high-dose group did not get the eighth shot because of dose-limiting toxicity, and another patient got only a single injection. All patients completed up to 48 weeks of follow-up.

The cytokine induced significant increases in immune cell counts that were sustained throughout the 48 weeks of follow-up, the researchers reported. Specifically:

• At 28 days, those in the low-dose group had a median gain of 118 CD4 cells (a 68% increase over baseline) and those in the high-dose group had a median gain of 576 cells (a 212% increase). The increases were significant at P=0.03 and P=0.02, respectively.
• At 12 weeks, median CD4 counts were 54% higher than baseline in the low-dose group and 130% higher than baseline in the high-dose patients. Both differences were significant at P<0.0001.
• At 48 weeks, median CD4 counts were 28% higher than baseline in the low-dose group and 75% higher than baseline in the high-dose patients. Both differences were again significant at P<0.0001.

A similar pattern was seen for CD8-positive T cells, the researchers said.

Administration of the cytokine was well tolerated, with transient and mild to moderate injection site reactions.

One patient in the high-dose group had a grade three increase in liver function enzymes, but aside from that no grade 3 or 4 adverse events were seen, the researchers said.

Dr. Levy and colleagues said new formulations of the cytokine now under development could allow an “optimized” therapeutic strategy that would be more convenient for patients.

They noted that a randomized controlled trial is needed to demonstrate the clinical benefits of interleukin-7.

In this study, in the highest dose group, four patients experienced transient increases in viral replication.

Primary source: Journal of Clinical Investigation

Source reference:

Levy Y, et al “Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment” J Clin Invest 2009; DOI: 10.1172/JCI38052.

Related Article(s):

• CROI: IL-2 Benefit in HIV Ruled Out

ATLANTA, March 25 — For treatment-naive HIV patients with an opportunistic infection, the benefits of immediate antiretroviral therapy outweigh the risks, according to new guidelines from the CDC.

• Explain to interested patients that many new HIV patients only learn of their infection when they seek treatment for an opportunistic disease.
• Note that guidelines for treatment of such diseases are revised periodically and explain that current guidelines make several changes aimed at improving treatment and prevention.

Evidence is mounting that for most such infections — especially if there is no specific treatment — early antiretroviral therapy will contribute to faster resolution, the agency said in an early release of Morbidity and Mortality Weekly Report.

The report contains revised guidelines — developed with the NIH and the Infectious Diseases Society of America — for prevention and treatment of opportunistic infections in adults and adolescents with HIV.

The new guidelines make several changes, the agency said, including:

• Greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of opportunistic infections, especially those for which no treatment exists
• Information regarding the diagnosis and management of immune reconstitution inflammatory syndromes
• Information on the use of interferon-gamma release assays for the diagnosis of latent tuberculosis infection
• Updates on drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB
• A new section on hepatitis B infection
• The addition of malaria to the list of infections that might be acquired during international travel

People often learn they have HIV only when they seek treatment for an opportunistic infection, the guidelines note, and physicians face the question of when to start antiretroviral therapy.

Starting effective antiretroviral therapy has been shown to speed resolution or at least stabilize diseases such as cryptosporidiosis, microsporidiosis, and progressive multifocal leukoencephalopathy. In the absence of specific therapy for Kaposi’s sarcoma, initiation of antiretroviral therapy has been documented to resolve lesions.

And, the guidelines say, starting effective antiretroviral therapy in the setting of an acute opportunistic infection also has a preventive effect — a second opportunistic infection is less likely to occur.

On the other hand, starting therapy has potential disadvantages, including:

• Severely ill patients might not absorb drugs well, leading to sub-therapeutic levels and the possibility of resistance
• Toxicities associated with the antiretroviral drugs might be confused with disease manifestations or toxicities associated with the medications used to treat the opportunistic infection
• Drug-drug interactions might be difficult to manage
• Renal or hepatic dysfunction associated with the opportunistic infection might make dosing of antiretroviral drugs difficult to estimate
• Immune reconstitution inflammatory syndromes can cause manifestations difficult to distinguish from other clinical conditions

Nevertheless, the guidelines say, for many opportunistic infections “the early benefits of [antiretroviral therapy] outweigh increased risk related to these other factors and [antiretroviral therapy] should be started as soon as possible.”

One exception is TB, the guidelines say, where it may be advisable to wait until TB treatment is completed.

The guidelines note that drug interactions between antiretroviral medications and rifamycin drugs can result in subtherapeutic levels of the anti-HIV drugs.

If rifampin is used, the guidelines say, the antiretroviral regimen should not include protease inhibitors and either an efavirenz- or nevirapine-based regimen is preferred.

On the other hand, rifabutin has a less potent effect and can be used — with appropriate dose adjustments — together with regimens based on protease inhibitors or nucleoside reverse transcriptase inhibitors.

The guidelines note that all HIV patients should be tested for latent TB infection, either with the traditional tuberculin skin test or the new interferon-gamma release assay.

There is evidence, the guidelines say, that compared with the skin test the new test — three are approved in the U.S. — is more consistent and has higher specificity, is better correlated with surrogate measures of exposure to M. tuberculosis, and has less cross reactivity because of Bacillus Calmette-Guérin vaccination or other nontuberculous mycobacteria exposure.

Nevertheless, the skin test can be used where resources are limited, the guidelines say.

The guidelines also add:

• Information regarding the diagnosis and management of immune reconstitution inflammatory syndromes
• A new section on hepatitis B virus infection
• Malaria to the list of infections that might be acquired during international travel
• Consideration of other geographic opportunistic infections
• Special considerations during pregnancy

Primary source: Morbidity and Mortality Weekly Report

Source reference:

Centers for Disease Control and Prevention “Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents” MMWR 2009; 58: 1-206.

BALTIMORE, March 25 — New results from a landmark randomized trial show that circumcision protects men against herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infection.

• Explain to interested patients that three major studies have shown that male circumcision protects against the acquisition of HIV.
• Note that this study — undertaken as part of the original three — now shows that the intervention protects against the acquisition of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV).

But the intervention had no apparent effect on the risk of acquiring syphilis, according to Thomas Quinn, M.D., of Johns Hopkins University, and colleagues.

Their study — conducted in Rakai, Uganda — was one of three that earlier showed circumcision of heterosexual men reduced the risk of acquiring HIV by 50% to 60%, Dr. Quinn and colleagues said in the March 26 issue of the New England Journal of Medicine.

Taken as a whole, they said, the research now indicates the benefits of male circumcision for STD control even as circumcision rates are falling in some of the most at-risk populations.

In an earlier part of the Rakai study, the researchers looked at other effects of circumcision, finding that it also reduced genital ulcer disease. For the latest analysis, they tracked syphilis, HSV-2, and HPV — three sexually-transmitted infections that are common worldwide.

The Rakai study actually consisted of two parallel but independent trials of circumcision that enrolled 5,534 HIV-negative, uncircumcised male volunteers ages 15 to 49 and assigned them randomly to get immediate circumcision (the intervention group) or after 24 months (the control group).

The researchers tested participants for HIV, HSV-2, and syphilis at baseline and at six, 12, and 24 months. They also performed physical examinations and conducted interviews. As well, a subgroup was tested for HPV infection at baseline and 24 months.

The researchers reported a significant benefit in terms of HIV acquisition later in 2006 and unveiled results showing the herpes benefit at a conference last year. (See: Circumcision Halves Risk of Heterosexual HIV Transmission and CROI: Circumcision Reduces Risk of Herpes Simplex-2)

Of the 3,393 volunteers who were negative for HSV-2 at enrollment, 1,684 were assigned to the intervention group and 1,709 to the control group, Dr. Quinn and colleagues said in the journal article.

The researchers found:

• At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group. The difference amounted to an adjusted hazard ratio in the intervention group of 0.72 (with a 95% confidence interval from 0.56 to 0.92) that was significant at P=0.008.
• On the other hand, there was no significant difference in acquisition of syphilis. The adjusted hazard ratio was 1.10, with a 95% confidence interval from 0.75 to 1.65.

In the subgroup tested for HPV, the baseline prevalence of high-risk genotypes in the study arms was similar — 38.1% in the intervention group and 37.1% in the control group.

At 24 months, however, the prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group. That amounted to an adjusted risk ratio of 0.65 (with a 95% confidence interval from 0.46 to 0.90) that was significant at P=0.009.

Dr. Quinn and colleagues noted that the power of the HPV finding is limited by the fact that it was confined to a subgroup of the study population.

Nonetheless, they argued, there is now good evidence that “male circumcision reduces the risk of several sexually-transmitted infections in both sexes.

“These benefits,” they concluded, “should guide public health policies for neonatal, adolescent, and adult male circumcision programs.”

Indeed, the power of the study — taken with other evidence — is such that it should inform public policy, said Matthew Golden, M.D., and Judith Wasserheit, M.D., both of the University of Washington in Seattle.

For a host of sexually-transmitted diseases, “circumcision offers an important prevention opportunity and should be widely available,” they said in an accompanying editorial.

They noted that circumcision rates in the U.S. are falling, especially among groups such as blacks and Hispanics, where rates of HIV, herpes, and cervical cancer are “disproportionately high.”

“These new data should prompt a major reassessment of the role of male circumcision, not only in HIV prevention but also in the prevention of other sexually-transmitted infections,” they said.

They noted that “The American Academy of Pediatrics, which previously concluded that evidence was insufficient to recommend routine neonatal circumcision, is reviewing its position in collaboration with other professional organizations.”

Primary source: New England Journal of Medicine

Source reference:

Tobian AAR, et al “Male circumcision for the prevention of HSV-2 and HPV infections and syphilis” N Engl J Med 2009; 360: 1298-309.

Additional source: New England Journal of Medicine

Source reference:

Golden, MR Wasserheit, JN “Prevention of viral sexually-transmitted infections — Foreskin at the forefront” N Engl J Med 2009; 360: 1349-1351.

Related Article(s):

• Circumcision Halves Risk of Heterosexual HIV Transmission
• CROI: Circumcision Reduces Risk of Herpes Simplex-2

NEW YORK, March 26 — Remarkable video images show HIV reaching out from an infected T cell to enter an adjacent uninfected cell, researchers here said.

The images, taken using quantitative, high-speed, three-dimensional video microscopy, provide new insight into how HIV propagates from cell to cell, according to Benjamin Chen, M.D., Ph.D., of Mount Sinai School of Medicine here, and colleagues.

In the video images, the virus is seen to reach out through “virological synapses,” forming “synaptic buttons” from which genetic material penetrates a target cell, Dr. Chen and colleagues reported in the March 26 issue of Science.

One implication of the study, Dr. Chen said, is that many of the inhibitors now used to treat HIV “may not be effective at blocking infection” through this process.

• Explain to interested patients that HIV infection can proceed in a cell-free manner or by direct transfer from an infected cell to a target cell.
• Note that this study used imaging techniques to follow the process of cell-to-cell transfer in detail, which may add insight into the process and perhaps lead to better treatments.

In vitro, Dr. Chen and colleagues noted, cell-to-cell infection can be a thousand-fold or more efficient than cell-free infection (in which a free-floating virus particle infects a cell). But exactly how the two processes differ has not been clear.

To help shed light on the issue, Dr. Chen and colleagues engineered an infectious HIV clone, in which the gene for the Gag protein includes the gene for green fluorescent protein, or GFP.

GFP, derived from jellyfish, glows green when exposed to blue light and is widely used in experiments to track genetic changes.

In this case, the altered Gag protein allowed the researchers to follow the path of their engineered HIV clone as it moved from cell to cell in the test tube.

When cells infected with the HIV clone were cultured with CD4-positive T cells, 24% of them formed stable adhesions to CD4 cells within four hours, the researchers found.

And after adhesion, 80% of the infected cells developed button-shaped Gag accumulations at the contact site within 82 minutes, on average.

Small particles of HIV Gag protein moved into the button, with speeds up to 0.8 micrometers per second, leaving a ring-shaped region of Gag depletion near the synapse.

During cell-to-cell transfer, the researchers saw fluorescent Gag emerge from buttons and penetrate the attached target cell, before being released inside and moving away at 0.12 micrometers per second on average.

The researchers were also able to show that in many cases, the infection was productive.

In one example, the cell with the fluorescent HIV clone adhered to a target cell for 18 hours before separating. At 32 hours, the target cell had a diffuse green glow, indicating productive infection.

Dr. Chen and colleagues found that the cell-to-cell transmission was inhibited by molecules that blocked the HIV co-receptors CXCR4 and CCR5, suggesting that the co-receptors are part of the process.

On the other hand, they found, an inhibitor that can block synapse-mediated viral transfer had little effect on cell-free HIV infection but inhibited productive infection by cell-associated HIV.

At the same time, they found, well-known patient antisera with polyclonal antibodies to HIV that can block cell-free infection did not efficiently block cell-to-cell transfer of the virus.

The findings have implications for vaccine research, Dr. Chen and colleagues said, because the cell-to-cell transfer depends on two cells adhering using the HIV Env protein — a process that might be interrupted.

Equally, they said, drug researchers might target factors involved in the formation of the viral synapses.

Primary source: Science

Source reference:

Hübner W, et al “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses” Science 2009; 323: 1743-1747.

TORONTO, April 1 — When it comes to HIV therapy, delay means death, an international team of researchers has concluded.

• Explain to interested patients that the weight of medical opinion has swung back and forth when it comes to the timing of HIV treatment for patients without symptoms.
• Note that this study suggests strongly that early treatment has a significant survival benefit.
• Point out however that observational data do not provide definitive proof and a randomized prospective clinical trial would be necessary to change therapy.

In a large observational cohort, delaying antiretroviral therapy — even when an asymptomatic patient’s immune system was still relatively strong — was associated with a significant increase in the risk of death from any cause, according to Mari Kitahata, M.D., of the University of Washington and colleagues.

The finding is based on an analysis of what happened to 17,517 asymptomatic and treatment-naive HIV patients in the U.S. and Canada who received medical care during the period from 1996 through 2005, the researchers said online in the New England Journal of Medicine.

Although the results do not come from a randomized trial, they seem likely to add impetus to a growing movement to start HIV treatment early, according to Paul Sax, M.D., and Lindsey Baden, M.D., both of Harvard Medical School.

The so-called NA-CCORD study “adds to a growing body of data supporting earlier treatment for HIV infection,” they said in an accompanying editorial in the journal.

Some of the data from the NA-CCORD study — involving patients from 22 research groups in more than 60 cities — was presented earlier this year. (See CROI: Early HIV Treatment Improves Survival)

Using statistical methods, Dr. Kitahata and colleagues were able to “mimic” a randomized trial using observational data.

They stratified patients based on their CD4-positive T cell count at diagnosis — between 351 and 500 cells per cubic millimeter or greater than 500 cells.

Current guidelines, proposed last year by the International AIDS Society-USA Panel, suggest a 350-cell level as the benchmark for initiating therapy in asymptomatic patients. (See IAC: HIV Care Guidelines Expand Treatment Eligibility)

Then the researchers looked at what happened to patients in each group who started therapy immediately compared with those who waited until their CD4 count dropped out of the stratum — below 351 and 500 cells per cubic millimeter, respectively.

In the first group, there were 8,362 patients with a CD4 count of 351 to 500 cells per cubic millimeter, and 2,084 (or 25%) initiated therapy while their cell count remained within that range. The remaining 6,278 (or 75%) deferred therapy.

After adjusting for factors such as calendar year, cohort of patients, and demographic and clinical characteristics, patients in the deferred-therapy group had an increase in the risk of death of 69%, compared with the early-therapy group.

The relative risk was 1.69, with a 95% confidence interval from 1.26 to 2.26, which was significant at P<0.001.

Results were even more striking in the second group, which included 9,155 patients with an initial CD4 count of greater than 500 cells per cubic millimeter.

Of those, 2,220 (or 24%) initiated therapy while their CD4 count was still within the stratum, and 6,935 (or 76%) delayed treatment.

Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% — a relative risk of 1.94, with a 95% confidence interval from 1.37 to 2.79, which was also significant at P<0.001.

At least part of the reason for the increased risk is contained in a range of recent studies showing that HIV infection worsens the outcomes of many illnesses not traditionally associated with the virus, such as cardiovascular disease, the researchers said.

The study is limited by its observational nature, Dr. Kitahata and colleagues said, which may have allowed unknown factors to interfere with the results.

Indeed, Drs. Sax and Baden said, only a full-scale randomized trial — and several are in the works — can actually account for all possible confounding factors.

For that reason, they argued, the results “cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy.”

Nonetheless, they said, “the supportive evidence for the benefits of earlier therapy continues to increase.”

On the other hand, Dr. Kitahata said earlier this year, the study may not have an immediate real-world impact. “One of the difficult things for us in our population of patients is that we see patients presenting very late in disease and even below 350 (CD4 cells per cubic millimeter),” she told MedPage Today.

Such delays — combined with the evidence of the benefit of early treatment — make “strategies to identify patients with HIV infection before the onset of substantial immunodeficiency all the more compelling,” Drs. Sax and Baden said.

Primary source: New England Journal of Medicine

Source reference:

Kitahata MM, et al “Effect of early versus deferred antiretroviral therapy for HIV on survival” N Engl J Med 2009; 360: DOI: 10.1056/NEJMoa0807252.

Additional source: New England Journal of Medicine

Source reference:

Sax PE Baden LR “When to start antiretroviral therapy - Ready when you are?” N Engl J Med 2009; 360: DOI: 10.1056/NEJMe0902713.

Related Article(s):

• IAC: HIV Care Guidelines Expand Treatment Eligibility
• CROI: Early HIV Treatment Improves Survival