HIV This Week

Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, Chand F, Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van Widenfelt E, Mazhani L, Novitsky V, Lagakos S, Essex M. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 2007;356:135-47.http://content.nejm.org/cgi/content/full/356/2/135

A single dose of nevirapine during labour reduces perinatal transmission of HIV-1 but often leads to viral nevirapine resistance mutations in mothers and infants. Lockman and colleagues studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan–Meier method. Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment. The authors conclude that women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine.

Editors’ note: These study results are encouraging because they suggest that the risk that single dose nevirapine will compromise subsequent treatment success for women can be reduced if antiretroviral treatment is started at least 6 months after childbirth. If confirmed by similar studies, these findings could have important implications for decisions about when to treat women post-partum; however, combining drugs for prevention of mother-to-child transmission would also reduce the risk of resistance and keep treatment options open for women.

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Garcia R, Badaro R, Netto EM, Silva M, Amorin FS, Ramos A, Vaida F, Brites C, Schooley RT. Cross-sectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients. AIDS Res Hum Retroviruses 2006;22:1248-52.

Antiretroviral therapy success is highly dependent on the ability of the patient to fully adhere to the prescribed treatment regimen. Garcia and colleagues present the results of a cross-sectional study that evaluates the predictive value of a self-administered questionnaire on adherence to antiretroviral therapy (ART). Study participants were interviewed using a 36-item Patient Medication Adherence Questionnaire (PMAQ) designed to assess knowledge about ART, motivation to adhere to treatment, and behavioural skills. Plasma HIV-1 RNA levels were correlated with the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were receiving their initial ART regimen. Of the remaining patients, 39 (21%) and 61 (34%) were on a second or additional ART regimen, respectively. An undetectable viral load was documented in 47/62 (76%) patients on their first regimen who reported missing medication on less than 4 days in the last 3 months. The Patient Medication Adherence Questionnaire had a higher predictive value of plasma viral suppression for patients in the initial regimen than for patients in salvage therapy. The overall predictive value of the Patient Medication Adherence Questionnaire to identify adherence was 74%, and 59% for nonadherence, with an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the concept of ART, 80% were failing or had previously failed the ART. Of 35 patients with doubts about their HIV status or skeptical of the benefits of ART, 29 (84%) were nonadherent. Despite the positive predictive value of PMAQ in identifying adherence, self-reported adherence is not a sufficiently precise predictor of treatment success to substitute for viral load monitoring. On the other hand, the use of such an instrument to identify factors associated with nonadherence provides an excellent opportunity to apply early intervention designed to specifically address factors that might be contributing to the lack of adherence prior to regimen failure.

Editors’ note: The relatively short administration time of this questionnaire which could assist in tailoring adherence counselling, suggests that it should be validated for use as a screening tool in other settings where patients are literate.