Lack of indinavir-associated nephrological complications in HIV-infected adults (predominantly women) with high indinavir plasma concentration in Abidjan, Côte d'Ivoire.

To report the tolerance of indinavir combined with ritonavir (IDV/r 800/100 mg) twice daily (bid) in sub-Saharan African HIV-infected adults. HAART-naives patients started zidovudine plus lamivudine plus IDV/r 800/100 mg bid. Follow-up included standardized documentation of morbidity, CD4(+) cell count, creatininemia, plasma HIV-1 RNA, and IDV minimal plasma concentration (C(min)) measurements at month 1 (M1), M3, and M6. Seventy HIV-1-infected adults (68 women, median CD4 235/mm(3)) started HAART. At M6, 63% had undetectable viral load, and the median gain in CD4 since baseline was +128/mm(3). During the first 6 months, 21 patients experimented with 23 treatment modifications (reduction in IDV/r 400/100 mg bid, n = 11; switch to efavirenz, n = 11; zidovudine replaced by stavudine, n = 1), including 22 for digestive intolerance and 1 for severe anemia. At M1, M3, and M6, 67, 59, and 48 patients were still receiving IDV/r 800/100 mg bid, of whom 70%, 72%, and 60% had IDV Cmin above 5 ng/ml, respectively. In these patients, at M1, M3, and M6, the mean (+/- SD) IDV C(min) were 3431 +/- 3835 ng/ml, 2288 +/- 2116 ng/ml, and 1543 +/- 2398 ng/ml, respectively. There was no renal insufficiency of any grade, and no symptoms of urinary stones. The IDV/r 800/100 mg bid-containing regimen led to high IDV Cmin and a high rate of digestive intolerance. There was a surprising lack of nephrological side effects during the 6 months of follow-up, supporting the hypothesis that nephrological tolerance of IDV might be higher in sub-Saharan African individuals than in Americans or Europeans.

Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with cotrimoxazole in Côte d'Ivoire.

OBJECTIVE: Neutropenia is the most frequent side effect of cotrimoxazole in sub-Saharan Africa. We estimated the incidence of haematological disorders during the first 6 months of a zidovudine-containing highly active antiretroviral therapy (HAART) regimen in sub-Saharan African adults receiving cotrimoxazole. METHODS: Prospective cohort study in Abidjan, with blood cell count measurement at baseline (HAART initiation), month 1, month 3 and month 6. RESULTS: A total of 498 adults [baseline: 80% currently on cotrimoxazole prophylaxis; median CD4 count 237/mm3 [interquartile range (IQR) 181;316]; median neutrophil count 1647/mm3 (IQR 1221;2256); median haemoglobin 113 g/l (IQR 102;122)] started zidovudine (AZT)/lamivudine/efavirenz. During follow-up, 118 patients had a grade 3-4 neutropenia [(56.3/100 person-years (PY)], 23 had a grade 3-4 anaemia (9.6/100 PY) and no cases of grade 3-4 thrombocytopenia. Of the 118 patients with grade 3-4 neutropenia, 86 (73%) had to stop cotrimoxazole because neutropenia persisted, and one (<1%) had to stop AZT because of persistent neutropenia after cotrimoxazole was stopped (neutropenia-related HAART modification: 0.4/100 PY). Of the 23 patients with grade 3-4 anaemia, 11 had to stop AZT (anaemia-related HAART modification: 4.4/100 PY). In patients who stopped cotrimoxazole but not AZT, the median gain in neutrophils at 1 month was +540/mm3 (IQR +150;+896). CONCLUSIONS: At baseline, most patients had a normal neutrophil count and 80% of them were already receiving cotrimoxazole. An unexpectedly high rate of grade 3-4 neutropenia occurred shortly after introduction of AZT. Almost all of the persistent severe neutropenia disappeared after cotrimoxazole was stopped. This suggests an accentuated drug interaction between the two drugs in these sub-Saharan African individuals. Grade 3-4 anaemia was much less frequent, but remained the first cause of AZT discontinuation.