HIV in Infants: What More Can Be Done?
More than 1 million Americans are living with HIV, according to HIV.gov. And while research has made great strides in reducing HIV prevalence and incidence around the world, more needs to be done about mother-to-child transmission and treatment options for newborns testing HIV-positive.
To shed some light on these gaps, Consultant360 spoke with Karin Nielsen, MD, MPH, who is a clinical professor of pediatrics in the Division of Infectious Diseases at the David Geffen School of Medicine at UCLA and UCLA Mattel Children’s Hospital. She also recently spoke about HIV in infants at the HIV & Hepatitis in the Americas 2018 conference.1
Consultant360: When is treatment for HIV-infected infants initiated? And what is the typical course of management?
Karin Nielsen: Treatment of infants depends on early diagnosis, which is crucial for early intervention. In most case scenarios, maternal HIV infection is identified before or during prenatal care, and therefore infants who are at risk for acquiring HIV are tested for the presence of virus at different time points in the first months of life, starting within 48 hours of birth. A positive molecular test for HIV in the infant should be confirmed by a separate second test as soon as possible, and if both molecular tests are positive, the diagnosis of HIV infection is confirmed, and treatment should be initiated.
It is important to remember that this has to be a molecular test such as an HIV polymerase chain reaction (PCR) assay because infants born to mothers with HIV have maternal antibodies to HIV in the first 15 months of life, and so they will test positive by regular antibody assays.
Treatment with antiretrovirals should be initiated as soon as the HIV diagnosis is confirmed. If the test result is positive at the time of birth, then treatment should be initiated at that time. Infants can have a negative PCR test for HIV at the time of birth and then develop a positive PCR test later, which reflects transmission at the time of labor and delivery. Testing by PCR for HIV in exposed infants, therefore, is performed at the time of birth, 2 weeks later, at 4 to 6 weeks of age, and periodically until completion of 4 months of age. At that point, if the child is not breastfed, a negative PCR test indicates the child is not infected.
In the second year of life, between 15 to 18 months of age, a standard antibody HIV-1 test is generally performed for children born to mothers with HIV, to document that at this age, antibodies to HIV are now negative. This is because, by this age, maternal antibodies to HIV should have disappeared from the child’s bloodstream.
So, in summary, initiation of specific and early antiretroviral treatment to the infant depends on close monitoring and testing for HIV in exposed infants in the first months of life. Treatment should be initiated as soon as possible and should be very potent to bring the virus load to undetectable levels over a short period of time. It is also important to distinguish HIV infant prophylaxis from HIV treatment of infants. All infants born to mothers with HIV receive at least one antiretroviral drug, generally zidovudine, for prevention of transmission started at the time of birth. This prophylaxis is continued for the first 4 to 6 weeks of life.
However, if the PCR test turns out to be positive, then the treatment is changed to 3 to 4 different antiretroviral drugs, at treatment-appropriate doses. Once the diagnosis of HIV is made and treatment initiated, these infants will need to be followed at very close intervals for dose adjustments of all antiretroviral drugs, which need to be made as the child grows. Long-term follow-up is also necessary for monitoring of HIV virus load, T-cell subsets, and potential antiretroviral toxicities. Infants exposed or infected with HIV also receive prophylaxis against opportunistic infections, generally cotrimoxazole starting at 6 weeks of life to prevent PCP, and are tested for other potential coinfections, such as cytomegalovirus (CMV), in the first days of life. Therefore, very close medical follow-up is needed in the first months of life.
C360: How can mother-to-child transmission be prevented?
KN: We have made significant progress in the prevention of HIV mother-to-child transmission in the last 2 decades. With prompt maternal recognition of HIV infection before or even during pregnancy, transmission can be decreased exponentially. Women who are aware of their HIV status normally continue on their antiretroviral medications throughout pregnancy without interruption until the time of delivery. Maternal treatment during pregnancy has decreased HIV transmission rates dramatically to less than 1% now-a-days.
Women should receive testing for HIV early during pregnancy, with prompt initiation of treatment if HIV infection is identified. Treatment should be initiated early, as transmission during pregnancy, which we call “in utero transmission,” can certainly occur and is dependent on the magnitude of maternal virus load. The higher the virus load, the higher the risk of transmission. Nevertheless, any time of initiation of treatment is better than not initiating treatment at all, and even women who present late in pregnancy should start prompt antiretroviral therapy.
Toward the end of pregnancy, it is important to keep in mind that continued therapy is important so that the drugs cross the placenta and protect the fetus from potential HIV exposure during the birthing process. Women with an unknown or a virus load greater than 1000 copies/ml in the blood close to the time of delivery should undergo an elective C-section, as this procedure has been shown to be effective in reducing HIV transmission during labor and delivery.
Also important is that in areas with high HIV prevalence, women should be tested again in the last trimester of pregnancy for HIV, as it is possible for women to acquire HIV during pregnancy as well. It is important to identify these patients as they are at very high risk of transmission without treatment.
One further prevents HIV transmission to the baby by having the baby take HIV prophylaxis in the first 6 weeks of life. The standard, as mentioned, is one drug, but in high-risk situations where the mother was not on treatment and the infant exposure was identified very late or right after delivery, one can still prevent transmission by providing 2 or 3 antiretrovirals to the infant, not as treatment but as prevention. This strategy has been demonstrated to work well in this situation.
Finally, there is still the risk of transmission of HIV by breastmilk. In the United States, the recommendation is for mothers with HIV to not breastfeed. However, in areas of the world where the risk of not breastfeeding outweighs the risk for HIV acquisition, the recommendation is to allow breastfeeding as long as the mothers are on adequate antiretroviral therapy and, ideally, with virologic suppression. Although the risk of HIV transmission is not zero in the breastfeeding scenario, it is a compromise for areas of the world where formula feeding is not safe for the infant.
NEXT: What is the next step for functional cure interventions? Is a “cure” for HIV in sight?
C360: What is the next step for functional cure interventions? Is a “cure” for HIV in sight?
KN: Most of the research in recent years has focused on reducing HIV viral reservoirs, either by treating infection very early, in which case the seeding of viral reservoirs is limited, or by strategies that have tried to purge viral reservoirs, an approach trying to eliminate HIV that is hidden in certain cells in the body. The problem with HIV is that it integrates in the human cell genome and hides inside certain cells, including cells of the central nervous system. Therefore, if we stop viral replication completely through the use of antiretrovirals, there is still latent virus. This virus can resurface and resume replication if, for any reason, antiretrovirals are stopped or stop working.
Completely eliminating integrated virus is a daunting task, so the approach is to try for a functional cure, which would be to eliminate virus without the need for antiretroviral treatment. In early treated infants, there are studies aiming to replicate the famous “Mississippi baby” who was infected early in life, stopped treatment unbeknownst to the medical team, and then maintained viral suppression for 27 months without any antiretroviral treatment. The virus eventually became detectable again. However, there are other infants and older children in similar circumstances in whom the virus has remained undetectable after treatment was stopped. In adults, this phenomenon has been seen in a group of patients called “elite controllers.”
There are new strategies evaluating long-acting treatments or broadly neutralizing antibodies that could potentially assist in the attainment of a functional cure. There is a case of an adult who received a bone marrow transplant with a cell type that is resistant to HIV, and after his transplant, HIV has not resurfaced. However, transplantation is not an option for the vast majority of people. Nevertheless, this demonstrated that a functional HIV cure can be attained.
C360: In your opinion, are HIV treatment guidelines most effective? Or do you think they need to be revised in any way?
KN: Treatment guidelines are updated periodically to reflect the evolving science in the field and to reflect new knowledge obtained from clinical trials, new drugs or new formulations, and different approaches. So, no guidelines are definitive. They always need to be eventually updated. In pediatrics, one of the major problems we have is lack of available formulations to treat infants very early in life. There are very few options for early treatment.
C360: What is the most common question you receive after presenting this session? And how do you respond?
KN: One of the most common questions is “How can one completely eliminate mother-to-child HIV transmission?” which is actually one of the WHO (World Health Organization) targets. We have come very far, with less than 1% transmission under optimal circumstances, but complete elimination of HIV transmission is likely not possible without an effective vaccine. As long as women are still becoming infected with HIV, the risk of mother-to-child transmission, even if minimal will continue to exist.
—Amanda Balbi, managing editor, Consultant360
Nielsen KA. Early treatment of HIV in infants. Paper presented at: HIV & Hepatitis in the Americas; April 19-21, 2018; Mexico City, Mexico. https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25093.