Early treatment appears to clear virus in second HIV-infected newborn

An HIV-infected newborn infant started on combined antiretroviral drug therapy just 4 hours after birth had no detectable viral load by 11 days of age and at 9.5 months of treatment appears to be HIV free, investigators have reported.

The case of the unidentified child, born in Los Angeles (L.A.) County, Calif., to a mother with untreated HIV infection, echoes that of the so-called Mississippi child. The latter case made headlines last year when investigators reported that, at the age of 26 months, a girl born with perinatal HIV infection had no detectable virus 10 months after stopping therapy with zidovudine (AZT), zidovudine (3TC), and nevirapine.

Dr. Deborah Persaud from Johns Hopkins Children’s Center in Baltimore, who presented the case of the Mississippi child at the Conference on Retroviruses and Opportunistic Infections (CROI) last year, reported an update on that case and described early results from the aforementioned L.A. child at this year’s CROI meeting.

As she reported in 2013, the Mississippi child was born to an HIV-infected mother with no evidence of antiretroviral therapy or prophylaxis during labor to prevent transmission to the infant.

The child was started on antiretroviral therapy at 31 hours of age with AZT, 3TC, and nevirapine given twice daily at 2 mg/kg per dose.

This regimen differed from the prophylactic regimen used in high transmission–risk situations, in which nevirapine is given in three doses at 0, 48, and 96 hours, Dr. Persaud noted. Investigators are still uncertain as to the optimal nevirapine dose for children under 2 weeks of age, she said.

At the most recent follow-up, the child was 41 months old and had been off combined antiretroviral therapy (cART) for 23 months.

"With respect to the Mississippi child, we can say that this child remains in remission. There’s no replication-competent T-cell reservoir to date, and it supports our hypothesis that very early treatment may prevent formation of critical reservoirs that currently preclude cure," she said.

Despite the apparent clearance of HIV in the Mississippi child, investigators continue to detect HIV proviral DNA in the child’s peripheral blood mononuclear cells.

"We’re not sure whether this is a real signal or really at the assay limits of detection, and it certainly requires continued follow-up and study. It’s important to point out that the clinical relevance of this detection remains unclear, but to date it does not signify impending rebound viremia," she said.

The investigators hypothesized that the residual microviral DNA seen in the child might be explained by maternal microchimerism, that is, residual maternal cells with HIV proviral DNA, but at 40-month follow-up, there was no evidence of maternal chimerism, Dr. Persaud said.

L.A. story

The L.A. child, whose sex was not disclosed, was born to a mother with untreated HIV infection and a high viral load (138,711 copies/mL) and low CD4 count (70 cells/mm³). At 4 hours of age, the child had a blood sample positive for HIV DNA, and at 36 hours, showed HIV RNA at 217 copies/mL.

A cerebrospinal fluid sample taken at 6 days to rule out sepsis showed HIV RNA at 32 copies/mL.

At age 4 hour, the child was started on a regimen of AZT, 3TC, and nevirapine, with the addition of lopinavir/ritonavir (Kaletra) at 2 weeks of age and was continued on this combination for 3.4 months. The child has since been maintained on the initial three-drug regimen.

"What we did find in this case is that by using clinical monitoring the viral load was undetectable by 11 days of age. Sequential samples collected through 9 months of age show undetectable plasma viral load," Dr. Persaud said.

The clinical assay used to diagnose infection found no detectable viral levels by 60 days of age, and the investigators have been unable to recover infectious virus from the child’s resting CD4 T cells at 1, 3, or 9 months.

However, when they looked at the noninduced proviral genome in a culture obtained at 1 month of age, the investigators detected HIV DNA at both days 7 and 14 of culturing, "but not at a level that we could amplify and sequence, so it’s unclear what those signals mean," she said.

Subsequent culture data have shown no detection of non-induced proviral genomes. The proviral DNA remains low. At last testing at 9 months of age, proviral DNA was less than 2 copies/mL in peripheral blood mononuclear cells, and the child had seroreverted and become HIV negative.

"I think we’ve shown that very early treatment, certainly in the Mississippi child, has led to sustained HIV remission now for up to 23 months off cART, and now with the second initiating treatment at 4 hours of life, this has led to rapid clearance of replicating virus and proviral DNA, supporting restriction of HIV spread with very early cART," Dr. Persaud said.

The work was supported by the Center for AIDS Research at Johns Hopkins University, the Foundation for AIDS Research (amfAR), and the National Institute of Allergy and Infectious Diseases.

An HIV-infected newborn infant started on combined antiretroviral drug therapy just 4 hours after birth had no detectable viral load by 11 days of age and at 9.5 months of treatment appears to be HIV free, investigators have reported.

The case of the unidentified child, born in Los Angeles (L.A.) County, Calif., to a mother with untreated HIV infection, echoes that of the so-called Mississippi child. The latter case made headlines last year when investigators reported that, at the age of 26 months, a girl born with perinatal HIV infection had no detectable virus 10 months after stopping therapy with zidovudine (AZT), zidovudine (3TC), and nevirapine.

Dr. Deborah Persaud from Johns Hopkins Children’s Center in Baltimore, who presented the case of the Mississippi child at the Conference on Retroviruses and Opportunistic Infections (CROI) last year, reported an update on that case and described early results from the aforementioned L.A. child at this year’s CROI meeting.

As she reported in 2013, the Mississippi child was born to an HIV-infected mother with no evidence of antiretroviral therapy or prophylaxis during labor to prevent transmission to the infant.

The child was started on antiretroviral therapy at 31 hours of age with AZT, 3TC, and nevirapine given twice daily at 2 mg/kg per dose.

This regimen differed from the prophylactic regimen used in high transmission–risk situations, in which nevirapine is given in three doses at 0, 48, and 96 hours, Dr. Persaud noted. Investigators are still uncertain as to the optimal nevirapine dose for children under 2 weeks of age, she said.

At the most recent follow-up, the child was 41 months old and had been off combined antiretroviral therapy (cART) for 23 months.

"With respect to the Mississippi child, we can say that this child remains in remission. There’s no replication-competent T-cell reservoir to date, and it supports our hypothesis that very early treatment may prevent formation of critical reservoirs that currently preclude cure," she said.

Despite the apparent clearance of HIV in the Mississippi child, investigators continue to detect HIV proviral DNA in the child’s peripheral blood mononuclear cells.

"We’re not sure whether this is a real signal or really at the assay limits of detection, and it certainly requires continued follow-up and study. It’s important to point out that the clinical relevance of this detection remains unclear, but to date it does not signify impending rebound viremia," she said.

The investigators hypothesized that the residual microviral DNA seen in the child might be explained by maternal microchimerism, that is, residual maternal cells with HIV proviral DNA, but at 40-month follow-up, there was no evidence of maternal chimerism, Dr. Persaud said.

L.A. story

The L.A. child, whose sex was not disclosed, was born to a mother with untreated HIV infection and a high viral load (138,711 copies/mL) and low CD4 count (70 cells/mm³). At 4 hours of age, the child had a blood sample positive for HIV DNA, and at 36 hours, showed HIV RNA at 217 copies/mL.

A cerebrospinal fluid sample taken at 6 days to rule out sepsis showed HIV RNA at 32 copies/mL.

At age 4 hour, the child was started on a regimen of AZT, 3TC, and nevirapine, with the addition of lopinavir/ritonavir (Kaletra) at 2 weeks of age and was continued on this combination for 3.4 months. The child has since been maintained on the initial three-drug regimen.

"What we did find in this case is that by using clinical monitoring the viral load was undetectable by 11 days of age. Sequential samples collected through 9 months of age show undetectable plasma viral load," Dr. Persaud said.

The clinical assay used to diagnose infection found no detectable viral levels by 60 days of age, and the investigators have been unable to recover infectious virus from the child’s resting CD4 T cells at 1, 3, or 9 months.

However, when they looked at the noninduced proviral genome in a culture obtained at 1 month of age, the investigators detected HIV DNA at both days 7 and 14 of culturing, "but not at a level that we could amplify and sequence, so it’s unclear what those signals mean," she said.

Subsequent culture data have shown no detection of non-induced proviral genomes. The proviral DNA remains low. At last testing at 9 months of age, proviral DNA was less than 2 copies/mL in peripheral blood mononuclear cells, and the child had seroreverted and become HIV negative.

"I think we’ve shown that very early treatment, certainly in the Mississippi child, has led to sustained HIV remission now for up to 23 months off cART, and now with the second initiating treatment at 4 hours of life, this has led to rapid clearance of replicating virus and proviral DNA, supporting restriction of HIV spread with very early cART," Dr. Persaud said.

The work was supported by the Center for AIDS Research at Johns Hopkins University, the Foundation for AIDS Research (amfAR), and the National Institute of Allergy and Infectious Diseases.

An HIV-infected newborn infant started on combined antiretroviral drug therapy just 4 hours after birth had no detectable viral load by 11 days of age and at 9.5 months of treatment appears to be HIV free, investigators have reported.

The case of the unidentified child, born in Los Angeles (L.A.) County, Calif., to a mother with untreated HIV infection, echoes that of the so-called Mississippi child. The latter case made headlines last year when investigators reported that, at the age of 26 months, a girl born with perinatal HIV infection had no detectable virus 10 months after stopping therapy with zidovudine (AZT), zidovudine (3TC), and nevirapine.

Dr. Deborah Persaud from Johns Hopkins Children’s Center in Baltimore, who presented the case of the Mississippi child at the Conference on Retroviruses and Opportunistic Infections (CROI) last year, reported an update on that case and described early results from the aforementioned L.A. child at this year’s CROI meeting.

As she reported in 2013, the Mississippi child was born to an HIV-infected mother with no evidence of antiretroviral therapy or prophylaxis during labor to prevent transmission to the infant.

The child was started on antiretroviral therapy at 31 hours of age with AZT, 3TC, and nevirapine given twice daily at 2 mg/kg per dose.

This regimen differed from the prophylactic regimen used in high transmission–risk situations, in which nevirapine is given in three doses at 0, 48, and 96 hours, Dr. Persaud noted. Investigators are still uncertain as to the optimal nevirapine dose for children under 2 weeks of age, she said.

At the most recent follow-up, the child was 41 months old and had been off combined antiretroviral therapy (cART) for 23 months.

"With respect to the Mississippi child, we can say that this child remains in remission. There’s no replication-competent T-cell reservoir to date, and it supports our hypothesis that very early treatment may prevent formation of critical reservoirs that currently preclude cure," she said.

Despite the apparent clearance of HIV in the Mississippi child, investigators continue to detect HIV proviral DNA in the child’s peripheral blood mononuclear cells.

"We’re not sure whether this is a real signal or really at the assay limits of detection, and it certainly requires continued follow-up and study. It’s important to point out that the clinical relevance of this detection remains unclear, but to date it does not signify impending rebound viremia," she said.

The investigators hypothesized that the residual microviral DNA seen in the child might be explained by maternal microchimerism, that is, residual maternal cells with HIV proviral DNA, but at 40-month follow-up, there was no evidence of maternal chimerism, Dr. Persaud said.

L.A. story

The L.A. child, whose sex was not disclosed, was born to a mother with untreated HIV infection and a high viral load (138,711 copies/mL) and low CD4 count (70 cells/mm³). At 4 hours of age, the child had a blood sample positive for HIV DNA, and at 36 hours, showed HIV RNA at 217 copies/mL.

A cerebrospinal fluid sample taken at 6 days to rule out sepsis showed HIV RNA at 32 copies/mL.

At age 4 hour, the child was started on a regimen of AZT, 3TC, and nevirapine, with the addition of lopinavir/ritonavir (Kaletra) at 2 weeks of age and was continued on this combination for 3.4 months. The child has since been maintained on the initial three-drug regimen.

"What we did find in this case is that by using clinical monitoring the viral load was undetectable by 11 days of age. Sequential samples collected through 9 months of age show undetectable plasma viral load," Dr. Persaud said.

The clinical assay used to diagnose infection found no detectable viral levels by 60 days of age, and the investigators have been unable to recover infectious virus from the child’s resting CD4 T cells at 1, 3, or 9 months.

However, when they looked at the noninduced proviral genome in a culture obtained at 1 month of age, the investigators detected HIV DNA at both days 7 and 14 of culturing, "but not at a level that we could amplify and sequence, so it’s unclear what those signals mean," she said.

Subsequent culture data have shown no detection of non-induced proviral genomes. The proviral DNA remains low. At last testing at 9 months of age, proviral DNA was less than 2 copies/mL in peripheral blood mononuclear cells, and the child had seroreverted and become HIV negative.

"I think we’ve shown that very early treatment, certainly in the Mississippi child, has led to sustained HIV remission now for up to 23 months off cART, and now with the second initiating treatment at 4 hours of life, this has led to rapid clearance of replicating virus and proviral DNA, supporting restriction of HIV spread with very early cART," Dr. Persaud said.

The work was supported by the Center for AIDS Research at Johns Hopkins University, the Foundation for AIDS Research (amfAR), and the National Institute of Allergy and Infectious Diseases.