Anthropometric and immunological success of antiretroviral therapy and prediction of virological success in west African adults.

OBJECTIVE: The 6 month assessment of the response to antiretroviral therapy (ART) is a critical step. In sub-Saharan Africa, few people have access to plasma viral-load measurement. We assessed the gain or loss in body mass index (BMI), alone or in combination with the gain or loss in CD4+ T-cell count (CD4), as a tool for predicting the response to ART. METHODS: In a cohort of 622 adults in Abidjan, Côte d'Ivoire, we calculated the sensitivity, specificity and predictive values of BMI and CD4 for treatment success defined as viral-load undetectability (< 300 copies/ml) as gold standard. FINDINGS: After 6 months of ART, the median change in BMI was an increase of 1.0 kg/m(2) (interquartile range, IQR: 0.0-2.1), the median change in CD4 an increase of 148/ml (IQR: 54-230) and 84% of patients reached viral-load undetectability. The distribution of change in BMI was similar among patients who reached undetectability and those who did not (increases of 1.06 kg/m(2) versus 0.99 kg/m(2), P = 0.51). With larger changes in BMI, the specificity for treatment success increased but its sensitivity decreased and its positive predictive value was stable around 85%. All results remained similar when combining changes in BMI with those in CD4 and when stratifying by groups of baseline BMI or CD4. CONCLUSION: In settings where viral-load measurement is not available, a high BMI gain does not reflect virological success, even when combined with a high CD4 gain. In our population, most patients with detectable viral-load had probably adhered to the drug regimen sufficiently to reach significant gains in body mass and CD4 count but had adhered insufficiently to reach viral suppression.

Tolerance and acceptability of an efavirenz-based regimen in 740 adults (predominantly women) in West Africa.

In sub-Saharan Africa, the position of efavirenz as a first-line nonnucleoside reverse transcriptase inhibitor remains to be discussed. We report here the 6-month efficacy and tolerance of an efavirenz-containing highly active antiretroviral therapy in a large cohort of HIV-1-infected adults. Seven hundred forty highly active antiretroviral therapy-naive adults (74% women; 14% with positive serum HBs antigen and 21% with abnormal baseline transaminase value) started zidovudine + lamivudine + efavirenz. At month 6, 1.2% of them were dead, 87% had undetectable viral load, and 7% had abnormal transaminase value. From months 1 to 6, the percentage of women who were actually using a contraceptive method increased from 58% to 80% (65% intramuscular progesterone and 35% oral estrogen/progesterone combination). The incidence of pregnancy was 2.6/100 woman-years (95% confidence interval, 0.67-4.51), and 86% of pregnant women voluntarily interrupted the pregnancy with no intervention on our part. Before month 6, only 0.8% of patients permanently discontinued efavirenz for severe adverse effects (neurologic, 0.6%; cutaneous, 0.1%; and hepatic, 0.1%). The leading cause of severe morbidity was tuberculosis. Considering the very high hepatic and cutaneous tolerance, efavirenz could be considered as a valuable first-line drug for women of childbearing age who agree to use contraception in sub-Saharan Africa, provided that the risk of teratogenicity should be closely monitored.

CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial.

BACKGROUND: Structured treatment interruptions of highly-active antiretroviral therapy (HAART) might be particularly relevant for sub-Saharan Africa, where cost-saving strategies could help to increase the number of patients on HAART. We did a randomised trial of structured treatment interruption in Abidjan, Côte d'Ivoire. METHODS: HIV-infected adults were randomised to receive continuous HAART (CT), CD4-guided HAART (CD4GT) with interruption and reintroduction thresholds at 350 and 250 cells per mm3, respectively, or 2-months-off, 4-months-on HAART. Primary endpoints were death and severe morbidity (any WHO stage 3 or 4 events and any events leading to death) at month 24. We report data from the CT and CD4GT groups until Oct 31, 2005, when the data safety monitoring board recommended to prematurely stop the CD4GT arm. Analyses were intention-to-treat. This study is registered at ClinicalTrials.gov, number NCT00158405. RESULTS: 326 adults (median CD4 count nadir 272 per mm3) were randomised to the CT or CD4GT groups and followed up for median of 20 months. Incidence of mortality (per 100 person-years) was not different between groups (CT 0.6, CD4GT 1.2; p=0.57). Incidence of severe morbidity (per 100 person-years) was higher in the CDG4T group (17.6) than in the CT group (6.7; p=0.001). The most frequent severe events were invasive bacterial diseases. 79% of severe morbidity episodes occurred in patients with CD4 count 200-500 per mm3. CONCLUSION: Patients on CD4GT had severe morbidity rates 2.5-fold higher than those on CT. This difference was mainly due to high rates of common diseases in patients with CD4 count 200-500 per mm3. This CD4-guided structured treatment interruption strategy should not be recommended in Abidjan.

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.