HIV and the Church

Written by Jeannie Wraight

 In March of 2013 at The Conference on Retroviruses and Opportunistic Infections (CROI 2013), scientists announced a baby girl in Mississippi was found to have cleared HIV through the use of antiretroviral therapy initiated within 36 hours after birth. This case drew a great deal of controversy, partially due to the media dubbing the baby 'cured of HIV'. Most involved in the case, and in HIV science and medicine, now call this baby a case of 'HIV remission'. Whether or not the Mississippi baby was indeed 'cured' of HIV, the case did bring significant attention and momentum to research into the very early initiation of ARVs in newborns.

The Mississippi baby's doctor, Deborah Persaud has continued to examine whether very early initiation of ARVs could promote HIV remission in other babies perinatally-infected with HIV.

 At CROI 2014 Dr. Persuad presented data on a second child, this one from California, who was also provided ARVs very soon after birth with the same results as the Mississippi baby. The child was confirmed HIV positive at 4 hours post-birth and was given zidovudine/lamivudine (Combivir) and nevirapine (Viramune). Lopinavir/ritonavir (Kaletra) was then added at 2 weeks and the full combination was given until 3.4 months of age. A viral load of 32 copies/mL was seen at day 6 which dropped to undetectable at day 11. At 9.5 months, the child was still receiving zidovudine/lamivudine and nevirapine and continued to have an undetectable viral load.

At 2.2 months, the California baby tested negative for HIV using an HIV DNA test. She then tested negative using a Western blot test at age 9 months. Despite the negative HIV results, both children show very low levels of persistent proviral DNA. The relevance of the detection of the proviral DNA is still unclear. 

The positive results of both of these children has helped spur the momentum for further studies. Clinical trials will begin shortly providing ARVs to newborns of HIV positive women who were not on antiretroviral therapy during their pregnancy. These infants will be given therapeutic doses of ARVs immediately following birth, instead of the smaller doses that are normally given during and after labor and birth. 

The goal would be to prevent the establishment of HIV proviral reservoirs. During initial HIV infection, some cells are infected with HIV but become inactive and do not replicate. This essentially hides them from the immune system and makes them unreachable to ARVs. It is thought that if ARVs are started immediately following birth that these reservoirs may be prevented from forming.

Deborah Persaud presented an abstract entitled "Virologic Control by 1 Year of Age Significantly Reduces HIV-1 Reservoirs in Perinatal Infection," in which she and colleagues tackled the questioned of how much could the proviral reservoirs be reduced in perinatally-infected children. This study is a step towards finding some of the answers we seek regarding latent reservoirs and early ART. 

Persaud and colleagues examined proviral viral load in peripheral mononuclear cells (PBMCs) in 144 perinatally-infected children (PHIV) enrolled in the Pediatric HIV/AIDS Cohort Study/Adolescent Master Protocol (PHACS/AMP). The children had been receiving antiretroviral therapy for a median of ten years. At the time of Persaud's study, the children were 8 to 20 years of age.

Researchers compared proviral burden, HIV serostatus, 2-LTR circles, and immune activation markers (soluble CD14, CD163, IFN-?, IL-6, and IL-1ß) by age at virologic control (less than 1 year, verses 1-5 years, verses greater than 5 years of age). In addition, proviral burden was correlated with HIV serostatus and 2-LTR circles and immune activation markers and compared in perinatally-HIV-exposed, uninfected (PHEU) children and perinatally infected children (PHIV).

Results showed that 46% of the children who suppressed viral load by age 1 compared to 11% of the children who suppressed viral load after age 1, had undetectable viral loads of less than <4 copies/million PBMC's. In addition, lower proviral burden was associated with undetectable 2-LTR circles (p<0.001) and HIV-1 seronegative/indeterminate status (p<0.001).

Results were similar across all three groups of virological control for plasma concentrations of soluble CD14, CD163, IFN-?, and IL-1ß, however sCD14 and IL1 ß levels were significantly higher in PHIV+ children than in PHEU (p<0.001 and p=0.004 respectively).

The authors concluded that, "Achieving virologic control by one year of age in perinatal infection leads to significantly smaller proviral reservoirs in those with HIV-negative or indeterminate serostatus and absent 2-LTR circles. It does not reverse immune activation. These findings emphasize the benefits of early therapy in perinatal infection with implications for a viro-immunologic profile for HIV cure-related clinical trials."

It is clear that 'curing' HIV or inducing remission of HIV, similar to what we see in cancer patients, will involve strategies directed at individual populations and not an all-in-one 'cure' for all people with HIV. Only time will tell whether these two children and other immediately treated perinatally-infected children will remain HIV-positive but it does appear that we are on the right track.

REFERENCE:

Virologic Control by 1 Year of Age Significantly Reduces HIV-1 Reservoirs in Perinatal Infection

Deborah Persaud et al