Impact of Drug Stock-Outs on Death and Retention to Care among HIV-Infected Patients on Combination Antiretroviral Therapy in Abidjan, Côte d'Ivoire

To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d'Ivoire.We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16).cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs

Diagram of main drugs affected by stock-outs in the Aconda program, February 2006–February 2008.

<p>CNTS: HIV care center affiliated with the National Center for Blood Transfusion. NVP: Nevirapine. ZDV-3TC: Zidovudine/lamivudine. * Proportion of patients who interrupt antiretroviral therapy = number of patients who interrupt therapy due to drug stock-outs/number on that therapy during this period. ¥ Month/day/year.</p

Factors independently associated with interruption in care or death among 405 HIV-infected patients whose initial cART regimen was affected by drug stock-outs, Abidjan, Côte d'Ivoire.

<p>HR: hazard ratio, adjusted for all variables in the table;</p><p>CNTS: HIV clinic affiliated with the National Center for Blood Transfusion;</p><p>ZDV: zidovudine; 3TC: lamivudine; d4T: stavudine; EFV: efavirenz; NVP: nevirapine.</p><p>Other cART regimens: zidovudine-lamivudine-indinavir/ritonavir, lamivudine-stavudine-indinavir/ritonavir, or stavudine-abacavir-efavirenz.</p><p>Other reasons for modifications are: adverse events, tuberculosis, pregnancy and treatment failure. The reason for modification was unknown for 18 patients (6%).</p><p>Other reasons for discontinuations are: travel, adverse events, funeral, treatment with traditional remedies, or inability to pay for drugs. The reason for discontinuation was unknown for 657patients (79%).</p><p>Virologic failure: plasma HIV RNA>300 copies/ml.</p><p>*Overall p value.</p><p>**The sensitivity analysis uses an expanded definition of drug stock-out, which includes any treatment discontinuation that lasted more than one month, was not accompanied by an explanation in the medical record, occurred when the pharmacy reported a shortage of at least one of the drugs in the patient's cART regimen.</p

Reasons for treatment modifications and discontinuations, by period, in 1,554 HIV-infected adults who started cART in HIV care centers of the Aconda program in Abidjan, Côte d'Ivoire.

<p>*: The total number of patients who modified their treatment is 280. Total of cART modifications, different from 280 because patients can undergo several modifications.</p>†<p>: Travel, adverse events occurrence, funeral, treatment with traditional remedies, inability to pay for drugs.</p

Factors independently associated with interruption in care or death among 975 HIV-infected patients in care 6 months after cART initiation, Abidjan, Côte d'Ivoire; basecase and sensitivity analysis on drug stock-out definition.

<p>HR: hazard ratio, adjusted for all variables in the table;</p><p>CNTS: HIV clinic affiliated with the National Center for Blood Transfusion;</p><p>ZDV: zidovudine; 3TC: lamivudine; d4T: stavudine; EFV: efavirenz; NVP: nevirapine.</p><p>Other cART regimens: zidovudine-lamivudine-indinavir/ritonavir, lamivudine-stavudine-indinavir/ritonavir, or stavudine-abacavir-efavirenz.</p><p>Other reasons for modifications are: adverse events, tuberculosis, pregnancy and treatment failure. The reason for modification was unknown for 18 patients (6%).</p><p>Other reasons for discontinuations are: travel, adverse events, funeral, treatment with traditional remedies, or inability to pay for drugs. The reason for discontinuation was unknown for 657patients (79%).</p><p>Virologic failure: plasma HIV RNA>300 copies/ml.</p><p>*Overall p value.</p><p>**The sensitivity analysis uses an expanded definition of drug stock-out, which includes any treatment discontinuation that lasted more than one month, was not accompanied by an explanation in the medical record, occurred when the pharmacy reported a shortage of at least one of the drugs in the patient's cART regimen.</p

Baseline characteristics of 1,554 HIV-infected adults who started cART in HIV care centers of the Aconda program in Abidjan, Côte d'Ivoire.

<p>*χ² test; † Wilcoxon rank-sum test.</p>‡<p>Numbers do not add up to 1,554 because of missing values.</p><p>CNTS: HIV clinic affiliated with the National Center for Blood Transfusion;</p><p>ZDV: zidovudine; 3TC: lamivudine; d4T: stavudine; EFV: efavirenz; NVP: nevirapine.</p><p>Other cART regimens: zidovudine-lamivudine-indinavir/ritonavir, lamivudine-stavudine-indinavir/ritonavir, or stavudine-abacavir-efavirenz.</p><p>BMI: Body Mass Index; virological failure: plasma HIV RNA>300 copies/ml.</p><p>IQR: Inter quartile range.</p