Factors Associated with Mother-to-Child Transmission of HIV-1 Despite a Maternal Viral Load

Factors Associated with Mother-to-Child Transmission of HIV-1 Despite a Maternal Viral Load <500 Copies/mL at Delivery: A Case-Control Study Nested in the French Perinatal Cohort (EPF-ANRS CO1)

The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 is as low as 0.5% in non–breast-feeding mothers who delivered at term while receiving antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20% of the infected children born during the period 1997–2006 in the French Perinatal Cohort. We aimed to identify factors associated with such residual transmission risk.

We performed a case-control study nested in the aforementioned subpopulation of the French Perinatal Cohort.

Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included. Case patients and control subjects did not differ by geographical origin, gestational age at HIV diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients were less often receiving treatment at the time that they conceived pregnancy than control subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500 copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7% vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a multivariate analysis at 30±4 weeks adjusted for viral load, CD4⁺ T cell count, and time at antiretroviral therapy initiation, viral load was the only factor independently associated with MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5–553; P<.001).

Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV-1. Guidelines should take into account not only CD4⁺ T cell count and risk of preterm delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during pregnancy.

To evaluate the risk of late postnatal HIV-1 infection in nonbreastfed children enrolled in the French ANRS Cohort CO01 (EPF).

The EPF cohort has prospectively enrolled HIV-infected mother/child pairs with a low proportion of known breastfeeding (<0.2%). Children were followed until they were 24 months old, with HIV-1 DNA/RNA PCR tests performed at birth, M1, M3 and M6 and a late serology at 18-24 months. This substudy included 4539 children who were uninfected at the age of 6 months in 1984-2005.

Five children were late diagnosed with HIV-1 infection despite negative PCR tests until 6 months. In three cases, the infection was diagnosed between 14 and 18 months. The other infections were diagnosed at 10 and 12 years of age because of AIDS-defining symptoms; their last (negative) serologies were performed at 19 and 9 months, respectively. A phylogenetic study performed in the latest case revealed a strong homology between the mother and child strains. No known mode of viral transmission (including breastfeeding or use of premasticated food) could be found. However, we observed previously reported risk factors for intrafamilial HIV-1 transmission: poor socioeconomic backgrounds and sustained HIV-1 viremia in the mothers during the follow-up of their children.

Late postnatal HIV-1 infection can rarely be diagnosed in the absence of known breastfeeding in high-income countries. Our results highlight the need for a maintained close follow-up of the noninfected children even after 6 months, especially when there are risk factors for intrafamilial viral transmission.

Arch Intern Med. 2010 Mar 8;170(5):410-9
Triple-Class Virologic Failure in HIV-Infected Patients Undergoing Antiretroviral Therapy for Up to 10 Years.
The PLATO II Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Group

BACKGROUND

Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades.

We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed.

Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF.

The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.