Viral load decline in pregnant women: faster in West Africans and those on nevirapine

Women who begin potent anti-HIV therapy during pregnancy achieve undetectable viral loads more quickly with nevirapine-based compared to nelfinavir-based regimens, according to findings from the European Collaborative Study. Results published in the June 15^th issue of Clinical Infectious Diseases also showed that women of western African origin achieved viral suppression more quickly than non-African women.

Many HIV-positive women receive their diagnosis during pregnancy, and therefore begin HIV therapy while pregnant. So far, clinical trials have not shown which specific regimens might achieve the best response in HIV-positive pregnant women. This report presented comparative data from women in the European Collaborative Study (an ongoing observational cohort study, established in 1985).

A total of 1,346 participants receiving potent anti-HIV therapy gave birth between 1997 and 2004. Only those who were treatment-naïve at conception, and who had a detectable viral load on study entry and at one or more follow-up points, were included for analysis - a total of 240 women. This multicentre study included women from a variety of birthplaces, but the majority (55%) were born in Africa. (32% were European-born, 10% from the Americas.) Fifty-nine percent of the participants were black, and 90% of these were born in sub-Saharan Africa. Median age was 29 years, median viral load was 4.16 log₁₀ copies/ml, and median CD4 count was 328 cells/mm³.

All 240 women began treatment therapy during pregnancy – 14 (6%) in the first trimester, 168 (70%) in the second, and 58 (24%) in the third. Eighty-four women (35%) received NNRTI-based therapy (the NNRTI, in all cases, was nevirapine). The remaining 156 (65%) received protease inhibitor-based regimens: 80% of these included nelfinavir; the others contained (in order of frequency) ritonavir, indinavir, saquinavir, or lopinavir/ritonavir. The proportion of nevirapine-based regimens increased over time (from 16% between 1997 and 2000, to 44% in 2003 and 2004). Most (89%) received a dual NRTI backbone of AZT and 3TC.

There were no significant differences between black and non-black women in terms of baseline viral load, CD4 counts, or type of ART used; however, black women tended to start HIV treatment later (median 24 weeks vs. 20.5 weeks, p≤.01; median 23 weeks overall). The PI and NNRTI groups were also similar, except for lower baseline CD4 counts in those who received PIs (305 vs. 355 cells/mm³, p=.02).

Of the 240 women, 175 (73%) had undetectable viral loads at the time of delivery, and the remainder generally had very low viral loads. This did not vary significantly between treatment groups. However, the time it took to achieve undetectable viral load varied with baseline viral load, treatment type, and place of origin.

Women on PI-based treatment took an estimated 1.38 times longer than those on nevirapine-based treatment (95% CI, 1.04–1.83) to reach viral suppression. The relative hazard (RH) for time to viral suppression was 1.54 (95% CI, 1.05–2.26) for nevirapine compared to PI-based treatment. Western African women also reached viral suppression more quickly, with a relative hazard of 1.90 (95% CI, 1.16–3.12) compared to non-Africans. As expected, baseline viral loads were also associated with longer time to suppression, but baseline CD4 cell count was not.

The researchers note that a “disadvantage of cohort data is their limited contemporary relevance when therapeutic practices have changed over time.” In this case, therapeutic guidelines now recommend that nevirapine not be prescribed for women with CD4 counts greater than 250 cells/mm³ due to risk of liver toxicity. The study subanalysis of women with CD4 counts less than 250 “indicates that our results may be generalizable but had limited statistical power.”

The COMBINE study (Podzamczer 2002) found equivalent responses to nevirapine and nelfinavir (with a dual nucleoside backbone) in pregnant women. However, the authors of the current study state that theirs “is the first to suggest that choice of initial HAART regimen has implications for timely achievement of undetectable viral load during pregnancy,” and “strongly suggest that an ART-naïve pregnant woman with a CD4 cell count 3” should begin nevirapine- rather than nelfinavir-based antiretroviral therapy, as well as “highlight[ing] the urgent need for further research of the pharmacokinetics, efficacy and safety of ART during pregnancy.”