ARV treatment following singe dose nevirapine exposure
Polly Clayden, HIV i-Base
There have been concerns (backed up by findings from Jourdain et al showing an impaired response among previously nevirapine exposed women to subsequent nevirapine containing HAART at six months ) that previous single dose nevirapine exposure in MTCT strategies will prejudice subsequent treatment options.
At last years retrovirus conference, Lyn Zijenah and coworkers reported 16 week data from 51 women receiving a generic nevirapine containing combination of AZT/3TC and nevirapine. The study compared virologic response between women who had previously received single dose nevirapine (n=21) or short course AZT (n=30) to reduce mother to child transmission . This Zimbabwean study also reported results for 33 men receiving the same treatment.
At week 16, of the women for whom viral load results were available, the number with undetectable virus <500 copies/mL, was 26/30 exposed to short course zidovudine and 12/13 exposed to single dose nevirapine.
The investigators reported despite growing concern about the impact of maternal prophylaxis on subsequent treatment, in this early analysis of women with subtype C, previously exposed to single dose nevirapine, these women were no more likely than those receiving AZT short course to have an impaired treatment response to nevirapine-containing HAART.
Two posters at this conference (one showing longer follow up from the Zimbabwean study) reported findings from groups of previously nevirapine exposed, nevirapine containing HAART treated women.
In the report from Lyn Zijenah and coworkers, 84 patients (52 women and 32 men) had reached 48 weeks of treatment by December 2005 . Of the women 20 and 32 had previous exposure to single dose nevirapine and short course AZT, more than a year prior to initiation of HAART, respectively.
In this analysis at 16 weeks the proportion of women (75.9%) with viral load <400 copies was lower than that for men (93.9%), p=0.031. At 48 weeks, the proportion of women (69.2%) with viral load <400 copies/mL was not significantly different from that of men (81.3%), p=0.221. Using a detection limit of viral load<50 copies/mL, 48.1% women had undetectable viral load compared to 68.8% of men, p=0.064. The authors reported no significant differences in virological response between women previously exposed to single dose nevirapine or to short course AZT, though out the 48 week study period, p>0.300.
Coovadia and coworkers from Johannesburg, South Africa compared response to treatment with nevirapine, 3TC and d4T among women exposed to single dose nevirapine18 to 36 months previously with unexposed women with prior live births in the same interval .
The authors reported that at 24 weeks, 65 nevirapine-exposed and 40 unexposed women, had good response to treatment. Time from delivery were a median 25 months (range 16-36 months) and 19 months (range 12-36 months), respectively. 48/48 nevirapine-exposed and 17/23 unexposed women had viral load <50 copies/mL. The baseline characteristics of the two groups were similar although the nevirapine exposed women had lower median viral load than the unexposed group: 90,400 copies/mL vs 177,000 copies/mL respectively.
The authors wrote: NNRTI based treatment should be retained as first line treatment options for this group of women.
This study will follow a target group of 90 exposed and 60 unexposed women for 96 weeks of treatment.
Both studies, Zijenah et al and Coovadia et al, are reassuring. Early to medium term virological outcome does not appear to be compromised in these cohorts if NNRTI-containing HAART is commenced more than 1 year after single dose nevirapine for PMTCT.
However some have raised concerns about the women vs men below 50 copies/mL, 48 week data in the Zijenah study (48.1% women compared to 68.8% of men, p=0.064), which although not significant, may show a trend.
Larger and longer studies are needed and it would be useful to see further follow up from Jourdain et al.
- Jourdain G, Ngo-Giang-Huong N,Tungyai P et al. Exposure to intrapartum single-dose nevirapine and subsequent maternal six-month response to NNRTI-based regimens. 11th CROI 2004. Abstract 41LB.
- Zijenah L, Kadzirange G, Rusakaniko R et al. Community-based generic antiretroviral therapy following single-dose nevirapine or short-course AZT in Zimbabwe. 12th CROI. Abstract 632.
- Zijenah L, Kadzirange G, Rusakaniko S et al. Community-based generic ART following single-dose nevirapine or short-course zidovudine in Zimbabwe. 13th CROI, Denver, 2006. Abstract 544.
- Coovadia A, Marais B, Abrams E et al. Virologic Response to NNRTI treatment among women who took single-dose nevirapine 18 to 36 Months earlier. 13th CROI, Denver, 2006. Abstract 641.