Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda

Griensven, Johan van; Zachariah, Rony; Rasschaert, Freya; Mugabo, Jules; Atte, E; Reid, Tony

doi:10.1016/j.trstmh.2009.07.009

Cited by 46 publications

(54 citation statements)

References 15 publications

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“…Previous studies have shown peripheral neuropathy associations with age consistently [35][36][37] and also with either weight or BMI; we observed higher peripheral neuropathy risk in heavier individuals comparable to previous studies [10,38]. Models including pre-ART BMI rather than weight gave similar inferences in our data (not shown).…”

Section: Aids 2014 Vol 28 No 17supporting

confidence: 89%

Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial

Kiwuwa-Muyingo

Kikaire²,

Mambule³

et al. 2014

Aids

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Objectives: We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART).Design: An open-label, multicentre, randomized trial. Methods:Peripheral neuropathy was self-reported at 12-weekly clinic visits. Cox regression models (excluding participants reporting preexisting peripheral neuropathy at ART initiation), considered sex; pre-ART WHO stage, age and CD4 þ cell count; CD4 þ cell count versus no CD4 þ cell count monitoring; and time-updated CD4 þ cell count, weight and use of stavudine, isoniazid and didanosine.Results: Four hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895 participants without preexisting peripheral neuropathy was 4.9 (4.7-5.4) years. Three hundred and fifty-four (12%) took stavudine as first-line substitution and 518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%) participants developed a new peripheral neuropathy episode, an incidence of 2.12 per 100 personyears. Eighteen (0.1%) had a grade 3/4 episode. Independent predictors of peripheral neuropathy were current stavudine use [adjusted hazard ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06-5.66], current isoniazid use [aHR 1.59 (95% CI 1.02-2.47)] and current didanosine use [aHR 1.60 (95% CI 1.19-2.14)]. Higher risks were independently associated with higher pre-ART weight [aHR (perþ5 kg) 1.07 (95% CI 1.01-1.13)] and older age aHR (per 10 years older) 1.29 (95% CI 1.12-1.49), but there was no significant effect of sex (P ¼ 0.13), pre-ART CD4 þ cell count (P ¼ 0.91) or CD4 þ cell count monitoring (P ¼ 0.73).Conclusion: Current stavudine, didanosine or isoniazid use continue to increase peripheral neuropathy risks, as does older age and weight at ART initiation; however, we found no evidence of increased risk in women in contrast to previous studies. The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended. All patients receiving isoniazid, either as part of antituberculosis (TB) chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.

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Section: Aids 2014 Vol 28 No 17supporting

confidence: 89%

Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial

Kiwuwa-Muyingo

Kikaire²,

Mambule³

et al. 2014

Aids

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“…Combined with resistance tests, assessment of adherence may prove to be useful in developing countries [19] to preserve limited second line treatment. Genotypic resistance testing has been initiated in Rwanda [8,9,20] and close monitoring of patients at risk has been proposed as a relevant strategy [21]. To our knowledge, our study is the first study evaluating the utility of saliva in a Sub-Saharan population for which specific genetic background, medications and diet might influence differently antiretroviral pharmacokinetics both in plasma and saliva.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Saliva as an Alternative Matrix for Monitoring Plasma Zidovudine, Lamivudine and Nevirapine Concentrations in Rwanda

Gras¹,

Schneider²,

Karasi³

et al. 2011

CHR

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Saliva may provide interesting advantages as matrix for compliance measurements, pharmacokinetic studies and therapeutic drug monitoring in resource limited countries. We investigated the feasibility of using saliva for compliance monitoring of zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP) in 29 HIV-1 infected patients from Rwanda. ZDV, 3TC and NVP drug levels were quantified by an LC/MS-MS method in plasma and stimulated saliva samples and compared using Bland-Altman analysis. Seven patients demonstrated undetectable saliva ZDV levels while five out of these seven also showed no 3TC salivary concentrations. For the other samples, we observed a good agreement between salivary and plasma concentrations of each antiretroviral drug. A significant relation between the difference in saliva and plasma ZDV concentrations and the average ZDV concentration in the two matrices was deduced as follows: y = -380.15 + 1.79 x. The log saliva and plasma concentration difference of both 3TC and NVP was consistent across the range of average log concentration. Overall, we showed large agreement limits suggesting a wide inter patient variability that may result in non-reliable plasma level predictions from saliva drug measurements. Therefore, our results indicate that saliva may serve as a valuable tool only for NVP compliance testing because of its high salivary concentration.

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“…Some authors described a relationship between NVPinduced toxicity and ethnicity, 17 a history of drug allergy, 18 body mass index, 19 older age, 20 high ALT or AST level in plasma, 20 or a high CD4 count 21 before starting NVP, HCV, or HBV coinfection, 16 the carriage of the HLA-Cw8 antigen 22 or the HLA-DRB1*01 allele, 23 or mutations in MDR1 gen, 24 excessive alcohol consumption, 5 the concomitant use of PI 25 and pregnancy. 26 Other studies, evaluating the same variables, found antagonistic results.…”

Section: Discussionmentioning

confidence: 99%

Nevirapine-Associated Toxicity in Clinical Practice in Buenos Aires, Argentina

Bottaro

Huberman²,

Iannella³

et al. 2010

Journal of the International Association of Physicians in AIDS

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Objectives: To determine the incidence and risk factors for nevirapine (NVP)-associated toxicity in a cohort of HIV-infected people in Buenos Aires, Argentina. Design: Retrospective study. Methods: HIV-infected adults who received NVP-based highly active antiretroviral therapy (HAART) at least for 2 weeks between May 1997 and March 2008 were included in this study. We analyzed patients' age, gender, HIV transmission route, HIV disease stage, pregnancy, alcohol intake, adverse events, coinfection with hepatitis B or C virus, time until toxicity, and withdrawal rates. Results: A total of 1110 patients (631 men) were included. Rash was the most frequently observed adverse event; it was more frequent in women. The incidence of severe rash and hepatotoxicity was similar in women and men. Female sex was the only variable significantly associated with mild-to-moderate rash. High CD4 count, pregnancy, and chronic hepatitis were not associated with NVP-related toxicity. An undetectable viral load at the time of starting NVPtreatment resulted in a lower risk of NVP-related rash.

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Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda

Cited by 46 publications

References 15 publications

Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial

Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial

Evaluation of Saliva as an Alternative Matrix for Monitoring Plasma Zidovudine, Lamivudine and Nevirapine Concentrations in Rwanda

Nevirapine-Associated Toxicity in Clinical Practice in Buenos Aires, Argentina

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