Viral load rebounds in women who start Tx during pregnancy or postpartum

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Approximately one-third of HIV-positive women who attain viral suppression after starting antiretroviral therapy (ART) during pregnancy experience a significant rebound in viral load in the year after giving birth, according to results of a South African study.

“The key findings are that up to one-third of women who achieve initial viral suppression experience viremia within one year postpartum, and that most of these women experience VL [viral load] > 1000 copies/mL, often with repeated episodes over time,” comment the investigators led by Professor Landon Myer, head of the division of epidemiology & biostatistics at the School of Public Health and Family Medicine at the University of Cape Town. “The high incidence of viremia on ART in routine care documented here is of clear concern and has significant implications for the population-level impact of policies for universal ART.”

In low- and middle-income countries, the World Health Organisation Option B+ strategy calls for universal, lifelong ART for all HIV-positive pregnant women, regardless of CD4 count. The numbers of HIV-positive pregnant or postpartum women starting ART has increased three-fold in the past five years.

There are concerns about adherence to ART among pregnant and postpartum women. Several studies have demonstrated significant levels of disengagement from HIV care among postpartum women. However, data concerning viral load control among women who started HIV treatment during pregnancy are limited.

An international team of investigators therefore designed a study to examine patterns of viral control in pregnant and postpartum women who started ART during pregnancy and used routine health services in Cape Town, South Africa.

The 523 women included in the analysis were enrolled in the prospective MCH-ART cohort. Viral load was monitored separately from routine clinic visits. Viral suppression was defined as maintenance of a viral load below 50 copies/ml; a minor viraemia was viral load between 50 and 1000 copies/ml and major viraemia was a viral load above 1000 copies/ml.

The participants had a median age of 28 years. On average ART was started during the 21st week of pregnancy. A quarter of the cohort had taken a previous short course of antiretrovirals for the prevention of mother-to-child transmission and 3% had stopped taking a previous course of ART. Median CD4 count and viral load at the point of ART initiation were 345 cells/mm3 and 8000 copies/ml, respectively.

After initial viral suppression, the participants contributed a total of 5092 women-months of follow-up; 86% of this observation was postpartum. The median number of post-suppression viral load tests was five per person.

Overall, 70% of women maintained viral suppression throughout the follow-up period, with 8% having a minor rebound in viral load and 22% experiencing major viraemia. The majority of women with major viraemia had two or more viral load measurements above 1000 copies/ml.

The proportion of women with elevated viral load measures increased steadily with time after initial viral suppression. Cumulatively, one year after giving birth, 37% of women in the study had had at least one viral load above 1000 copies/ml. Median peak viral load was approximately 6500 copies/ml, close to the pre-therapy viral load peak.

Factors associated with higher incidence of major increases in viral load were younger age (18 to 22 years vs 34 years and older, IRR = 3.67; 95% CI 1.78-7.56), starting ART during third trimester (vs first trimester, IRR = 2.21; 95% CI 1.13-4.34), stopping a previous ART regimen (IRR = 2.94; 95% CI 12.9-6.69) and postpartum follow-up (vs antenatal follow-up, IRR = 6.40; 95% CI 1.54-26.69). Analysis restricted to the postpartum period showed that each additional month of follow-up was associated with an 11% increase in the incidence of viraemia (IRR = 1.11; 95% CI 1.07-1.15).

The authors note that the incidence of viral breakthrough observed in their study is similar to that seen in studies conducted in richer settings.

“The parallels across countries in findings of high levels of viraemia in HIV-infected women during the postpartum period despite ART are striking, and may point to cross-cutting psychological, social and/or behavioural drivers of ART non-adherence during this phase of women’s lives,” suggest the authors. “Understanding why levels of viraemia on ART appear so consistent across settings in this patient population remains a critical question for optimising treatment programmes globally.”

Abstract
Background: The numbers of HIV-infected women initiating antiretroviral therapy (ART) in pregnancy are increasing rapidly with global policy changes. There are widespread concerns about ART adherence during pregnancy and postpartum but few data on viral suppression (VS) over time in these populations.
Methods: We followed a cohort of 523 women in Cape Town, South Africa initiating ART in pregnancy (once daily tenofovir 300mg, emtracitabine 200mg and efavirenz 600mg) and achieving VS (1000 copies/mL) and minor (50-1000 copies/mL) viraemic episodes (VE) and factors associated with major VE.
Results: In the cohort (median age, 28 years; median pre-ART VL, 3.99 copies/mL; 3% previously defaulted ART; 24% with previous exposure to short-course antiretrovirals) the median time of follow-up from VS was 322 days. Overall, 70% maintained VS throughout follow-up, 8% experienced minor VE only, and at least one major VE was documented in 22% of women. In women with VE, peak viremia (median, 3.79 log10 copies/mL) was linearly related to pre-ART VL. The incidence of major VE after initial VS was independently associated with younger age, ART initiation during the third trimester, previous defaulting on ART and postpartum follow-up.
Discussion: Viraemia appears to occur frequently, particularly postpartum, among HIV-infected women after initial VS in this setting. More intensive VL monitoring is warranted in this population while the immediate causes and long-term implications of VE require investigation.

Authors
Landon Myer, Lorna Dunning, Maia Lesosky, Nei-Yuan Hsiao, Tamsin Phillips, Greg Petro, Allison Zerbe, James A McIntyre, Elaine J Abrams

Aidsmap material
Journal of Clinical Infectious Diseases abstract


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