Increased incidence of symptomatic peripheral neuropathy among adults receiving stavudine- versus zidovudine-based antiretroviral regimens in Kenya

McGrath, Christine J.; Njoroge, Julia W.; John‐Stewart, Grace; Kohler, Pamela; Benki-Nugent, Sarah; Thiga, Joan; Etyang, Anthony; Chung, Michael H.

doi:10.1007/s13365-012-0098-x

Cited by 9 publications

(8 citation statements)

References 22 publications

(37 reference statements)

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“…We found, as has been shown in other studies, that stavudine significantly increased the risk of peripheral neuropathy [9,10,[22][23][24]. The association of didanosine with peripheral neuropathy is also consistent with previous studies from high-income countries [5].…”

Section: Discussionsupporting

confidence: 92%

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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: Discussionsupporting

confidence: 92%

“…However, as above, overall, we observed a lower post-ART peripheral neuropathy incidence than more recent studies in Africa [22,23,32,33] and one USA study [34].…”

Section: Discussionsupporting

confidence: 75%

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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“…Side effects and toxicity-related treatment discontinuation may be more frequent for d4T compared to ZDVcontaining ART. 58,59 Despite this finding, rates of overall virologic suppression were not statistically inferior when comparing d4T + 3TC and ZDV + ddI with non-nucleoside reverse transcriptase inhibitor (NNRTI) 59 or indinavir-containing ART 60 in previous studies. TDF-containing regimens have been shown to be better tolerated and have fewer side effects than d4T-containing ART but comparably effective.…”

Section: Discussionmentioning

confidence: 96%

Early Warning Indicators for First-Line Virologic Failure Independent of Adherence Measures in a South African Urban Clinic

Marconi

Hampton

et al. 2013

AIDS Patient Care and STDs

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We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after ‡ 5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL) > 1000 copies/mL] and controls (2:1) if they had VL £ 1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF ( p < 0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures.

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“…In addition to the main analysis above, which evaluated the patients’ individual-level characteristics as predictors of dropout, we evaluated whether initial ART regimens (based on the backbone drug received) predicted risk of dropout. As some previous studies suggest that TDF- or D4T-based regimens may be more associated with negative outcomes than AZT-based regimens [ 22 , 28 ], we compared risk of dropout in patients receiving AZT-based regimens (as the reference) to dropout risk in those receiving either TDF-based or D4T-based regimens. In this analysis, we suspected that, at a minimum, sex, age, and year of ART initiation, would be confounders of associations between initial regimen and dropout.…”

Section: Discussionmentioning

confidence: 99%

Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa

et al. 2015

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BackgroundIn sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up.MethodsIn a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05.ResultsData from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4 % had CD4+ T-cell counts <100 cells/μL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9 % (established cumulative mortality = 2.3 %, loss to follow-up = 24.6 %), 5.6 % were transferred to other service providers, and 67.5 % were retained in care. A diagnosis of Kaposi’s sarcoma (hazard ratio (HR) = 3.3, 95 % CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95 % CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95 % CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus ≥13.8 g/dl (HR = 1.9, 95 % CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss ≥10 %; reduced total lymphocyte count; chronic diarrhea; male sex; young age (≤28 years); and marital status.ConclusionsAmong HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting.

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Increased incidence of symptomatic peripheral neuropathy among adults receiving stavudine- versus zidovudine-based antiretroviral regimens in Kenya

Cited by 9 publications

References 22 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

Early Warning Indicators for First-Line Virologic Failure Independent of Adherence Measures in a South African Urban Clinic

Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa

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