• No HCV transmission occurred from 30 HIV/HCV co-infected pregnant women to their newborns.
• 63% took double or triple anti-HIV therapy.
• 23% took AZT (zidovudine, Retrovir) monotherapy only
• 70% had a cesarean ("C") section; none breastfed
• None of 30 newborns were HCV positive; 1 became HIV positive

A small study presented at the 36th EASL suggests that treating HIV during pregnancy and having a cesarean ("C") section might decrease HCV (hepatitis C virus) transmission to newborns. However, the study has some limitations. Dr. E. Minola and colleagues from Hospital Riuniti in Bergamo, Italy presented the results.

Previous studies reviewed by the author have shown that women infected with HCV have an approximate 4% risk of transmitting HCV to their newborns (range 0-6%). However, co-infected women have a higher risk of approximately 15% (range 0-36%). Yet, the women in most of those studies were not taking anti-HIV therapy. The purpose of this new study was to consider the potential benefits of anti-HIV therapy and elective cesarean section on HCV transmission to newborns of HIV/HCV co-infected, pregnant women.

A total of 17,308 pregnant women from Bergamo (Northern Italy) were included. Newborns of co-infected women were tested for HCV antibodies at 8 months of age, for HCV RNA (lower limit 1,000 copies per milliliter) at 12 months, HIV antibodies at 16 months, and HIV RNA at 20 and 24 months.

Among the 17,308 women, 519 (3%) were positive for HCV antibodies. A total of 51 of them were still pregnant at the time of analysis and therefore were excluded in the current, interim analysis. Among the remaining 468 women, 318 (68%) had a positive test for HCV RNA. Among those 318, 30 had HIV antibodies, indicating HIV/HCV co-infection among 9.4% of them. This also represented an HIV/HCV co-infection rate overall of 0.17% among all pregnant women. (Note the analysis showed that only women with a positive test for HCV antibodies were tested for HCV RNA and that only those with detectable HCV RNA were tested for HIV. It is likely that there were some women in the group who were HIV positive without HCV infection.) Among the first 283 women HCV positive women, 51% were genotype 1, 24% were genotype 2 and 20% were genotype 3. HCV genotype status was reported for the first 26 co-infected women and included 46% with genotype 1.

The median HIV RNA among the co-infected women was 636 copies, with a range of 50-58,920 copies per milliliter (cop/mL). The median HCV RNA of co-infected women was 4.6 million cop/mL, compared to 2.9 million cop/mL among HCV mono-infected women. However, this difference was not statistically significant (p=0.12). The percentage of co-infected women with an increased ALT (alanine aminotransferase, liver enzyme) at enrollment (during pregnancy) was 93%, compared to 57% of HCV mono-infected women (no statistical analysis reported). Whereas, an elevated ALT at delivery was present in 10% of co-infected and 5% of HCV mono-infected women. Only one of the co-infected women had a CD4 count less than 500 cells per microliter (assumed to be at delivery, with 87% taking some type of anti-HIV therapy). Delivery by cesarean section included 70% of co-infected and 20% of HCV mono-infected women.

Among the 30 co-infected women, 19 (63%) were taking double or triple anti-HIV therapy. (Triple meant HAART or highly active antiretroviral therapy whereby the third drug was a protease inhibitor or non-nucleoside drug, with 2 NRTI or nucleoside analog drugs.) At least half were taking triple therapy. Among the remaining 11 women (37%) not initially taking anti-HIV therapy, 7 of them (23% of the 30 co-infected women) started monotherapy with AZT (zidovudine, Retrovir) at the 12th week of pregnancy to help prevent mother-to-newborn transmission. (Note that monotherapy is substandard care for any HIV positive person, according to current guidelines, due to not being potent and the risk of developing drug resistance.) The remaining 4 women (13% of 30) refused even AZT monotherapy. None of the co-infected women breastfed.

The results were as follows. When considering the 30 HIV/HCV co-infected women, none of their 30 newborns were positive for HCV RNA when tested at age 2 years, indicating no HCV transmission. Only one newborn was HIV positive after age 2 years, indicating an HIV transmission rate of 3.3%. (No additional information was presented about this child, e.g. maternal HIV RNA and CD4 count at delivery, mother taking anti-HIV therapy or not, cesarean section or not, infant taking anti-HIV therapy or not.) The overall HCV transmission rate from HCV mono-infected mothers was 3.8% (11 of 288). (No additional information was presented about those 11 offspring, e.g. maternal HCV RNA at delivery, cesarean section or not, genotype.)

The authors concluded, "In this study, the risk of HCV mother-to-child transmission from HCV/HIV co-infected mothers was lower than that reported in earlier series." Also, "among several factors that may have contributed to the reduction of risk, it is reasonable to hypothesize that the progressive introduction of an effective antiretroviral [anti-HIV] therapy and of AZT chemoprophylaxis have played a relevant role." The authors continue, "Moreover, the increasing rate of elective cesarean section in the HIV infected women may have limited the potential spread of HCV."

The main limitation of the study is the small number of HIV/HCV co-infected, pregnant women. Also, the mild degree of HIV-related immune suppression (as indicated by only one women with a CD4 count less than 500 cells/mL) suggests that there was an overall low risk of HCV transmission to their newborns. Lowest (or at least pre anti-HIV therapy) CD4 counts were not presented, and this information would have been helpful. Therefore, in this small study, the relative benefits of anti-HIV therapy and cesarean section (and even to a very minor degree, not breastfeeding) in preventing HCV transmission are difficult to determine. A comment from someone present at the session was that it would have been helpful to present statistical "95% confidence intervals," which help to clarify the significance and statistical range of the findings. Lastly, it would have been helpful to have some additional specific information about the one HIV positive infant and the 11 HCV positive infants born to HCV mono-infected mothers, as indicated. Nonetheless, the findings may represent some potential significance of anti-HIV therapy, elective "C" section and not breastfeeding in helping to prevent HCV transmission to the offspring of HIV/HCV co-infected women.

Reference
Minola E and others. Lack of HCV transmission from HCV and HIV co-infected mothers on antiretroviral therapy to children. Abstract and oral presentation 140 at the 36th Annual Meeting of the European Association for the Study of the Liver (EASL 2001); April 18-22, 2001, Prague, Czech Republic and Journal of Hepatology 2001 April;34(suppl 1):3.