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Could an Integrase Inhibitor Have Prevented One More HIV Infection?

September 19, 2014

Monica Gomes, M.D., M.Sc.

Monica Gomes, M.D., M.Sc., is an infectious diseases and neurologist specialist who works at Hospital de Clínicas in Curitiba, Brazil. She is also assistant professor of the internal medicine department at the Federal University of Parana.


Difficulties to Preventing MTCT of HIV

When it comes to preventing mother-to-child transmission (MTCT) of HIV anywhere in the world, the target must be zero. Of course, we know that a lot of variables may affect the chain of events that can lead to an HIV-infected child.

HIV-infected women can transmit HIV to their children during pregnancy, delivery (the higher risk of transmission) and breastfeeding. As obstetricians, pediatricians and infectious disease specialists, we struggle to act properly during all steps of the chain -- from pregnancy to postnatal care -- to avoid one more HIV-infected child.

In Brazil, universal access to antiretrovirals has changed HIV care dramatically, with improvements in the rates of survival and decreasing rates of MTCT. Also, public programs that offer more efficient prenatal care make it possible to diagnosis HIV early and offer treatment for many STDs (sexually transmitted diseases), including HIV, thereby avoiding transmission to newborns.

But sometimes, things do not work properly. HIV-infected pregnant women must be diagnosed early enough to get an HIV drug-resistance test in order to receive the best combination of antiretrovirals. With the correct drugs, their viral loads decrease to undetectable in a couple of weeks, and must be kept under the limit of detection until delivery. When a pregnant woman comes to prenatal care later in pregnancy (also called "late-presenting"), things may get difficult. First, HIV transmission may already have occurred in utero, and second, if that's not the case, antiretroviral combinations need a few weeks to reach the goal of attaining an undetectable viral load. For these reasons, some treatment guidelines recommend specific strategies for these women.1

Antiretrovirals are not all equal regarding how fast they decrease viral load. Integrase inhibitors, with their high potency, have the property to decrease viral loads faster than some drugs from the other HIV drug classes (NNRTIs and PIs, for example).2 At the end of 48 weeks of follow-up, this higher potency may make no significant difference in overall treatment success, because if the aim is to maintain an undetectable viral load for a long period of time, tolerance becomes one of the most important characteristics of the drug that is being used. But in scenarios where time matters, such as advanced pregnancy in an HIV-infected woman, the ability to quickly achieve an undetectable viral load becomes a very important characteristic of the medication.


A Case Study

Facing the case of an HIV-infected pregnant woman who was off therapy and came to prenatal care at 30 weeks of pregnancy made us rethink the chain that leads to HIV transmission. She was started on AZT/3TC/LPV/r with no prior resistance tests (she had used the same regimen to avoid MTCT in another pregnancy three years earlier with success). After two weeks on AZT/3TC/LPV/r, she had a low but detectable viral load, so we decided to add raltegravir (RAL) to her regimen -- RAL was the only integrase inhibitor available in Brazil at that time.

The patient was informed that the scientific community had fewer safety data on RAL's use in pregnancy but, so far, the risk-benefit ratio in cases like hers suggested that it could be used.3 But, because integrase inhibitors are not readily available in Brazil for this indication, added with the bureaucracy that had to be overcome to justify the need for this drug, she was not able to add the fourth drug to her regimen and, at delivery, she had a low but detectable HIV viral load. All other pharmaceutical and obstetric strategies to prevent transmission were utilized (C-section, intrapartum AZT, antiretrovirals for the newborn, no breastfeeding).

Unfortunately, a couple of months later we learned that her baby had acquired HIV. Now, her baby is receiving treatment for HIV but the child has many HIV-related complications.

We felt very frustrated about the fact that we tried to offer all available tools to avoid this infection. Maybe the prevention chain failed in the beginning. Maybe the patient took too long to come to prenatal care. A lot of "maybes" come to our mind when we think about this HIV-infected child. But the worst "maybe" of all concerns the failure to add the fourth medication to the mother's treatment regimen. Would it have helped to avoid this MTCT? We'll never know.


Final Thoughts

In terms of HIV prevention, I really believe health professionals must offer all available tools, and not just one or another. And I sincerely hope that all HIV-infected women have access to effective HIV treatment so that there is not one more HIV-infected child in the world.


References

  1. EACS Guidelines 7.02. June 2014.
  2. Lennox JL, DeJesus E, Lazzarin A, et al., Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: A multicentre, double-blind randomised controlled trial. Lancet 2009;374(9692):796-806.
  3. Pinnetti C, Baroncelli S, Villani P, et al., Rapid HIV-RNA decline following addition of raltegravir and tenofovir to ongoing highly active antiretroviral therapy in a woman presenting with high-level HIV viraemia at week 38 of pregnancy. J Antimicrob Chemother 2010;65(9):2050-2052.


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See Also
What Did You Expect While You Were Expecting?
HIV/AIDS Resource Center for Women

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