Reducing maternal viral load during pregnancy is the most important factor in preventing mother-to-child transmission (MTCT) of HIV, results of a large study confirm. Other risk factors for MTCT included insufficient food, a recent sexually transmitted infection (STI) and a history of diseases associated with immune suppression.
The research was conducted in Malawi and involved women who did not take antiretroviral therapy (ART) until the onset of delivery. The transmission rate was 0.5% among women with a viral load below 1000 copies/ml, compared to 7.5% among women with a viral load above 10,000 copies/ml.
“Our study confirms that with maternal viral load suppression, most instances of perinatal MTCT can be avoided,” comment the authors. “These findings can help inform decisions to target populations for programmes seeking to improve coverage of ART during pregnancy, and may support efforts to recognise and treat maternal TB, STIs and other infection prior to and during pregnancy, and efforts to improve maternal nutritional status antenatally, to achieve worldwide elimination of paediatric HIV infection and improve outcomes for HIV-infected pregnant women.”
An estimated 150,000 children aged 15 years and younger were newly infected with HIV in 2015, mostly due to MTCT. Transmissions from mother to child can occur in utero, at the time of delivery or due to breastfeeding. ART during pregnancy and delivery dramatically reduces the risk of MTCT. However, despite massive increases in ART coverage, in 2014 an estimated 25% of pregnant women with known HIV infection did not receive ART.
Moreover, as a large number of HIV-positive women do not receive ART during pregnancy, it is important to identify the full spectrum of risk factors for MTCT.
Investigators from the Breastfeeding Antiretrovirals and Nutrition (BAN) study at the US Centres for Disease Control and Prevention, the department of epidemiology and biostatistics, School of Public Health, University of Witwatersrand, Johannesburg, UNC Project, Lilongwe, Malawi and the University of North Carolina Chapel Hill, conducted a retrospective analysis of the records of 2,275 HIV-positive pregnant women. Recruitment and follow-up took place between 2004 and 2010. Participants were required to be at least 14 years of age, ART naïve, planning to breastfeed and to have a CD4 cell count of at least 250 cells/mm3. The women did not receive any ART until the onset of labour, when the mothers and infants were provided with a single dose of nevirapine.
All the mothers also received twice-daily zidovudine and lamivudine from the onset of labour and for seven days after giving birth, with all infants receiving twice-daily weight-adjusted zidovudine and lamivudine for seven days.
The infants were tested for HIV via DNA PCR at birth and again at weeks one, two and four postpartum.
Approximately a third of women had a CD4 cell count below 350 cells/mm3 and 63% had a viral load above 10,000 copies/ml during pregnancy. Only 35% had more than a primary education. Anaemia during pregnancy, food insecurity and poor nutrition were all common and observed in over 40% of participants.
There were 119 cases of MTCT, with 115 occurring in utero, the remaining four cases in the first two weeks of life.
Women transmitting HIV to their infants had significantly higher median viral loads during pregnancy than women who did not transmit (61,830 copies/ml vs 16,529 copies/ml, p < 0.001). Of the 200 women who had a viral load below 1,000 copies/ml during pregnancy, there was only one case of MTCT, a transmission rate of 0.5%. Of note, there was a history of maternal TB infection in this case. The corresponding rate for women with viral loads between 1000 copies/ml to 10,0000 copies/ml was 1.4%, increasing to 7.5% for women with a viral load over 10,000 copies/ml. Women passing on HIV to their babies were also more likely than non-transmitting women to have a CD4 cell count below 350 cells/mm3 (36% vs 30%).
Shortage of food was more common among transmitting mothers than mothers who did not transmit (51% vs 41%). A history of TB was more prevalent among transmitters than non-transmitting (6.7% vs 2.8%), as was history of herpes zoster (14% vs 4%). Transmitters were less likely to have any formal post-primary education than non-transmitters (25% vs 35%).
After adjusting for potential confounders, viral load during pregnancy was the strongest risk factor for MTCT. Compared to a viral load above 10,000 copies/ml, a viral load below 1000 copies/ml was associated with a 90% reduction in the risk of MTCT (aOR = 0.1; 95% CI, 0.01-0.4), and a viral load between 1000 and 10,000 associated with an 80% reduction in the odds of transmission (aOR = 0.02; 95% CI, 1.2-2.6).
Other significant risk factors were: shortage of food (aOR = 1.8; 95% CI, 1.2-2.6); a self-reported STI in the previous 12 months (aOR = 1.9; 95% CI, 1.0004-3.7); a history of herpes zoster (aOR = 3.0; 95% CI, 1.6-5.6); and a history of TB (aOR = 2.5; 95% CI, 1.1-5.7).
The investigators note that while food insecurity may be a cause of nutritional deficiencies, previous randomised trials of nutritional supplements have not proven effective. It’s possible that food shortages in this study functioned as an indicator of social determinants of health.
They speculate that histories of TB and herpes zoster may have caused immunosuppression and brief, unobserved increases in viral loads. STIs may be associated with genital shedding of HIV.
“Clearly, every effort must be made to begin ART and reduce viral load in HIV-infected pregnant women,” conclude the authors. “Our data also suggest that food insecurity, history of diseases indicating immunosuppression, and history of other STIs may be risk factors for perinatal MTCT.”
Abstract
Objectives: To investigate potential risk factors for perinatal (intrauterine and intrapartum) mother-to-child transmission of HIV (MTCT) in women unexposed to Antiretroviral Therapy (ART) during pregnancy.
Methods: We compared factors according to perinatal MTCT outcome among 2,275 ART-naïve (until the onset of labor) HIV-infected women in the Breastfeeding, Antiretrovirals and Nutrition study (2004-2010) in Lilongwe, Malawi. Factors included HIV viral load during pregnancy, food security, demographic characteristics, hematologic and blood chemistry measures, medical history and physical factors. Associations with perinatal MTCT and interactions with maternal viral load were assessed using simple and multivariable logistic regression.
Results: There were 119 (115 intrauterine, 4 intrapartum) cases of perinatal MTCT; only one to a mother with <1,000 HIV copies/mL. Maternal viral loads >10,000 copies/mL were common (63.1%). Lower maternal viral load (<1,000 copies/mL and 1,000.1-10,000 copies/mL) was associated with reduced odds of perinatal MTCT [adjusted odds ratio (aOR), 0.1; 95% confidence interval (CI), 0.01-0.4 and aOR, 0.2; 95% CI, 0.1-0.4, respectively), compared with maternal viral load >10,000 copies/mL. Low CD4+ T cell count (≤ 350 cells/µL) was only associated with perinatal MTCT in unadjusted models. Food shortage (aOR, 1.8; 95% CI; 1.2-2.6), sexually transmitted infection (past year) (aOR, 1.9; 95% CI; 1.0-3.7), histories of herpes zoster (aOR, 3.0; 95% CI; 1.6-5.6) and tuberculosis (aOR, 2.5; 95% CI; 1.1-5.7) were associated with increased odds of perinatal MTCT.
Conclusions: These findings confirm that lowering maternal HIV viral load is most important in preventing perinatal MTCT, and support efforts to address food shortage, STD and TB prevention, while informing programs to improve ART coverage in pregnancy.
Authors
Ewing, AC; Ellington, SR; Wiener, JB, Chasela, CS; Tegha G; Nelson, JAE; Jamieson, DJ; van der Horst, C; Kourtis, AP
[link url="http://www.aidsmap.com/page/3368540/"]Aidsmap material[/link]
[link url="https://www.ncbi.nlm.nih.gov/pubmed/30379708"]The Pediatric Infectious Disease Journal abstract[/link]