Carolyn Colwell

An unknown South African boy may gain fame as the source of key clues to quelling the HIV virus. The announcement this summer of the boy’s 8-plus year survival after only 40 weeks of antiretroviral therapy (ART) in infancy has been heralded as a breakthrough.

The case strengthens hope for sparing HIV-infected children “the burden of life-long therapy and the health consequences of long-term immune activation” through a brief treatment period beginning in infancy, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), said.

The National Institutes of Health (NIH)-funded study showed how the currently 9-year-old boy received seemingly successful ART treatment among 252 HIV-infected infants. Infants were treated from between 6-12 weeks old up until the age of 2 years old. The 125-patient control group in the study had ART initiation delayed for a median of 40 weeks.

The surviving child had started ART 2007, at 32 days old. His high viral load was suppressed after 40 weeks of therapy.

Avy Violari, MD — co-leader of the study, head of pediatric research at the Perinatal HIV Research Unit at University of the Witwatersrand in Johannesburg, South Africa &mdash; said, to her knowledge, it was the first reported case of “sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy.”

Perhaps due to its rarity, the explanation for the child’s survival versus other trial patients is currently unknown. Caroline Tiemessen, PhD, head of cell biology at the Centre of HIV and STIs of the National Institute of Communicable Diseases (NICD) in Johannesburg, said further analysis of the survivor may bring a stronger understanding as to “how the immune system controls HIV replication.”

David W. Rosenthal, DO, PhD — Medical Director for the Center for Young Adult, Adolescent and Pediatric HIV for Northwell Health in New York &mdash; believed that a combination of genetic factors and unique immunological marker expressions “together may make a difference in this child.”

Although, according to the NIH, there have been at least 2 other long-term HIV survivors to have received ART at an early age, their treatment differed from the South African boy’s. His short dose period and extended period of time removed from ART treatment makes his case unique, Rosenthal said.

He, and other survivors, may hold genetic or immunological clues to suppressing the once-lethal virus.

“We ought to learn as much as we can about what makes these persons unique so we can find more therapeutic options that can be expanded to a larger population,” Rosenthal said.

Press releases were provided by NIH and the University of the Witwatersrand.

Articles

“We ought to learn as much as we can about what makes these persons unique so we can find more therapeutic options that can be expanded to a larger population.”

How a South African Boy with HIV Has Survived More Than Eight Years

With the goal of preventing HIV transmission and disease progression, federal guidelines since early 2012 have suggested everyone who tests HIV positive should start on anti-retroviral treatment (ART).

Not everyone does. A new study concluded that its findings from data drawn from the pre-100% guideline era can be helpful in reducing the percentage of non-compliant patients now.

Unexpectedly, the study found that the demographic characteristics of patients who failed to initiate ART within 2 years of entering care were not as important as clinical factors.

“Higher CD4 count, lower viral load, and a prevalent AIDS diagnosis were clinical characteristics associated with delayed ART initiation," researchers wrote. "Gender, age, race/ethnicity, and HIV risk factors such as reported male-to-male sexual contact and injection drug use were not associated with delayed ART initiation.”

Over the 10-year study period, the only clinical factor associated with failure to initiate ART was lower viral load.

“Despite the known benefits of early antiretroviral therapy initiation, a lower viral load measurement may continue to be an important clinical characteristic in the more recent era with current ART initiation guidelines," researchers wrote. "These findings provide a target for closer monitoring and intervention to reduce disparities in HIV care."

The research was based on data for 4,907 HIV patients enrolled in 8 clinics across the country between January 2003 through December 2012 — for whom treatment was strongly-to-moderately recommended. All of the test subjects had not previously been on ART.

At the beginning of their inclusion in the study, these patients had CD4 counts of 350 cells/mm or below. CD4 cells are the white blood cells that kill infections like HIV. A normal count is considered to be in the 500 to 1,500 range. AIDS may be diagnosed when that count drops below 200.

Those with a CD4 count of at least 200 cells/mm at the beginning of their participation in the study were 1.3 times as likely to delay ART than those with counts of less than 200. From 2003 through 2012, 54.6% of the participants with CD4 counts less than 200 did not initiate ART.

Viral load is measured by the number of HIV RNA. A viral load is 10,000 HIV RNA per milliliter of blood and high load would be 100,000. At the beginning of their participation, patients with viral loads of less than10,000 were more likely to delay ART than those with a viral load of at least a 100,000. Across the entire study period, 26.3% of those with viral loads of 10,000 or less did not start ART and 37.3% of those with viral loads of 100,000 or more also were not ART initators.

An AIDS diagnosis also was not necessarily compelling in terms of many AIDS positive participants not initiating ART. In the group that started in 2003 to 2007, 64.3% did not begin ART. In the group that started participating in the study in the 2008 to 2012 period, 74.1% with AIDS diagnoses were not initiators.

“Though guidelines also recommended ART initiation for patients with an AIDS diagnosis, it is possible that our findings that a prevalent AIDS diagnosis was associated with delayed ART initiation could have resulted from a lower engagement in care,” researchers wrote.

Enrollment date was the only demographic factor that appeared to affect the willingness to start ART, according to the study.

Six percent of the participants who did not initiate ART within 2 years of enrolling died. In 2014, 12,333 people died of AIDs-related causes in the US, according to the US Centers for Disease Control and Prevention (CDC). ART has been credited increased longevity for people who are HIV positive, and making it more of a chronic condition than a terminal one.

"This prolonged delay in ART intiation among patients with moderate to strong recommendation under past guidelines suggests that treatment practice under current guidelines recommending therapy initiation to all HIV-seropositive patients should be carefully scrutinized," researchers wrote. "The tendency to delay therapy in those patients with lower viral load may still persist despite clear evidence of the benefits of immediate therapy initiation."

Risk factors for delayed antiretroviral therapy initiation among HIV-seropositive patients

Lesbian, Gay, Bisexual Adults Report Greater HIV Test Rates, Worse Health

One-third of Low Viral Load HIV Patients Avoid Treatment

5 HIV Breakthroughs Coming Down the Pipeline

A study found that the demographic characteristics of patients who failed to initiate ART within 2 years of entering care were not as important as clinical factors.

Who Resists Starting ART Therapy for HIV?

Long-term treatment with antiretroviral therapy (ART) may really be a reprieve from a death sentence for many people diagnosed with HIV, according to a new British study.

“These results suggest that many people on ART will not have viral rebound over their lifetime,” author Andrew Phillips, PhD, a [rofessor of epidemiology and biostatistics at the University College London, wrote. 

The rates of viral rebound in people with long-term viral suppression on first-line regimens have become "extremely low," according to the study.

The study noted that most HIV patients who start on ART now achieve viral suppression within 3 to 6 months. The findings showed that, for those who are adherent to a first-line medication regimen started after 2008, the rebound rate is not only low but declines over at least 7 years before stabilizing at a low level — "as low as 1% per year in some demographic groups."

The 1% rate took into account that many viral rebounds are temporary, which the study defined as a single measurement of 200 copies per milliliter, followed up by a later measurement of 50 copies per milliliter or less.

Higher rates of viral rebound were found among black African men (about 1.88%) and women (about 1.65%) and among those with higher viral loads (about 1.04%) and higher CD4 counts (about 1.04%) before initiating ART. The study speculated that the reasons for increased risks for black African men and women might relate to "socioeconomic conditions or inconsistent prioritization of ART adherence over other challenges of daily life.”

The authors were uncertain about the cause of the higher rates among those with higher initial viral loads and CD4 counts.

The groups with the lowest rates of risk for viral rebound were older and started ART at a more recent date. Older age is associated with better mediction adherence, accoridng to the study. Starting ART more recently might reduce the risk because newer medications are less toxic and more effective and easier for patients to tolerate and manage.

The study offered several potential  explanations for the decreasing rates of viral rebound, which included that over time people integrate taking anti-retroviral drugs into their daily routine and the possibility that “viral suppression can be maintained with decreasing adherence over time.”

The causes of viral rebound after years of suppression are unknown, but researchers noted they had found no evidence "for a limit of durability of ART efficacy.”

The study was based on a test population of 16,101 drawn from The UK Collaborative HIV Cohort (UK CHIC) which provided data from people with HIV who were seen at least once at 21 clinics from throughout the United Kingdom.

Participants were included in the study if they were 16 or older, started ART with a regimen of at least 3 anti-retroviral drugs for the first time between January 1, 1998 and May 31, 2013, and had at least 9 months of follow-up after initiating ART. The median number of viral load measurements per patient was 7.

Limitations regarding its findings included the inability to extrapolate the results to people who do not have an initial positive virological suppression with ART or who are receiving second or more lines of ART, according to the study. It also did not take into account factors that could affect adherence such as socio-economic status, drug and alcohol use, mental health status or incarceration.

Nonetheless, with the number of people on ART worldwide approaching 20 million, the study said its findings are “of public significance worldwide.”

Long-term durability of HIV viral load suppression

Opioid Threat Grows to National Emergency, Study Shows Mortality Rates Are Even Worse

The rates of viral rebound in people with long-term viral suppression on first-line regimens have become "extremely low," according to a study.

How Long Will HIV Viral Suppression Last?

In 2014, practically half of HIV patients in the US were in remission, according to the latest data recently released by the US Centers for Disease Control and Prevention (CDC). That statistic may be only half the story.

While the national split is a significant jump from previously reported rates, the degrees of the success vary in different parts of the country, Barry S. Zingman, MD, Medical Director, AIDS Center, Montefiore Health System, told 

At his Center for Positive Living/ I.D. Clinic in The Bronx, NY, among the 3,300 HIV patients in treatment, the viral suppression rate is greater than 85%, and going up every year. Zingman said many other sites "around the country are seeing viral suppression rates in the 80s and 90s and that’s gratifying to see."

By contrast, the Centers for Disease Control and Prevention (CDC) statistics show some states such as Virginia and South Dakota only 34.3% and 40.4% of people with HIV 13 years of age and older, respectively, have achieved viral suppression, Zingman said.

The whole Montifiore system tests about 50,000 people a year in The Bronx and the southern part of nearby Westchester County, Zingman explained. It finds about 150 HIV infections annually. Overall, there are 24,000 people in The Bronx carrying the HIV virus, which means this area has more HIV cases than 41 states.

Increased testing has been a major US goal for increasing diagnosis, care, and the rate of suppression. Whether that happens depends to a large degree upon the characteristics of an area where someone lives — income, jobs, access to care.

People retaining medication regimens and continued care is crucial, Zingman said. Because Medicaid is the key insurer in the US, Mediciad expansion states "have shown greatly increased rates in viral suppression compared with the non Medicaid expansion states."

“If people can get insurance, they want to take care of this," Zingman said. "They know these are life saving therapies that we have.”

The improvement in anti-retroviral therapies (ART) for HIV is also a source of increased HIV suppression among the 1.1 million people in the US living with HIV, Zingman suggested. The doubt about whether ART can suppress viral load has been replaced with certainty in the last 5 years. In addition more ART regimens can involve only one pill a day and side effects are significantly lower than 7 or 8 years ago.

As the CDC has highlighted, there are still miles to go get consistent care for some population groups. For example, only 27% of young people with HIV had the virus suppressed, according to the CDC analysis of the latest data.

Due to "more unstable lives," reaching young people with HIV has been a persistent issue, Zingman said.

“They are a particular focus for engaging them in care and keeping them in care, and enabling them to stay on medication better, and they are also the group most at risk for transmitting HIV to others," Zingman said.

 regarding the suppression rates was made available.

While the national split is a significant jump from previously reported rates, the degrees of the success vary in different parts of the country, Barry S. Zingman, MD, Medical Director, AIDS Center, Montefiore Health System, told MD Magazine.

Carolyn Colwell

Articles

Latest News