Adrien Sawadogo

BACKGROUND: Epidemiologic data suggest that infection with herpes simplex virus type 2 (HSV-2) is associated with increased genital shedding of human immunodeficiency virus type 1 (HIV-1) RNA and HIV-1 transmissibility. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of HSV suppressive therapy with valacyclovir (at a dose of 500 mg twice daily) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2; all were ineligible for highly active antiretroviral therapy. The patients were followed for 24 weeks (12 weeks before and 12 weeks after randomization). Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment, adjusting for baseline values, and to evaluate the effect over time. RESULTS: A total of 140 women were randomly assigned to treatment groups; 136 were included in the analyses. At enrollment, the median CD4 cell count was 446 cells per cubic millimeter, and the mean plasma viral load was 4.44 log10 copies per milliliter. With the use of summary-measures analysis, valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidence interval [CI], 0.21 to 0.80) and in the mean quantity of the virus (log(10) copies per milliliter, -0.29; 95% CI, -0.44 to -0.15). However, there was no significant decrease in detection of HIV (risk ratio, 0.93; 95% CI, 0.81 to 1.07). HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log(10) copy per milliliter (95% CI, -0.72 to -0.35). Repeated-measures analysis showed that these effects became significantly stronger during the 3 months of follow-up. CONCLUSIONS: HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women. This finding may have important implications for HIV control. (ClinicalTrials.gov number, NCT00158509 [ClinicalTrials.gov].).

We analysed whether mutations associated with resistance to antiretroviral (ARV) drugs circulate among treatment-naive HIV-1-infected individuals at a period when these drugs started to become more widely available in Africa. Overall, major resistance mutations in the pol gene, as defined by the International AIDS Society Resistance Testing-USA panel, were observed in 16 treatment-naive individuals. Eight of the 97 patients tested in Burkina Faso bore mutations conferring resistance to one drug class of ARV drugs: two to nucleoside reverse transcriptase inhibitors (NRTIs; M41L [n = 1], M41L+T69S [n = 1]), four to non-NRTIs (NNRTIs; V106A/V [n = 1] and V1081 [n = 3]) and two to protease inhibitors (PIs; L33F [n = 2]). In Cameroon, resistance mutations were identified in 8 of 102 patients: three to PIs (M461/L [n = 2], L33F [n = 1]), three to NRTIs (T69N/T [n = 1], M184V [n = 1], A62V [n = 1]) and two to NNRTIs (P236L [n = 1], V1081 [n = 1]). It is important to note that not all genotypic drug-resistance algorithms give similar interpretations to the observed mutations. Population surveillance for ARV drug resistance is required and should be included in all implementation programmes.

INTRODUCTION: Gender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso. METHODS: We performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART. RESULTS: Of 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77-3.60; p<0.001). CONCLUSIONS: Men on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to determine the causes for their vulnerability in order to optimize HIV care. From now on, efforts should be made to support the adherence of men to ART in the African setting.

It has been reported that people living with HIV in West Africa exhibited the highest risks for chronic kidney disease (CKD) in the world. Here, we aimed at determining the CKD frequency and changes in kidney function during antiretroviral treatment (ART) in a large cohort of HIV-patients followed in Burkina Faso. We included ART-naive adults who initiated ART at the Day Care Unit of the Souro Sanou University Hospital between 01/01/2007 and 12/31/2016. We assessed the estimated glomerular filtration rate (eGFR) by serum creatinine using the Modification of Diet in Renal Disease (MDRD) equation. Following the K/DOQI recommendations, CKD was defined as eGFR < 60 ml/min/1.73m2 at two consecutive measurements at least 3 months apart. The factors associated with eGFR decline or CKD were identified by mixed linear regression and Cox regression, respectively. Three thousand, one hundred and thirty-eight patients (72% women) were followed for a median (IQR) of 4.5(2.2–6.9) years. At baseline, median eGFR (IQR) was 110.7(94.4–128.4) ml/min/1.73m2 and 93 (3%) patients exhibited eGFR < 60 ml/min/1.73m2. The lowest-performing progressions of eGFR during the first year of ART were observed in patients with 40-49 yr. age range (− 8.3[− 11.7;-5.0] ml/min/1.73m2, p < 0.001), age ≥ 50 yr. (− 6.2[− 10.7;-1.8] ml/min/1.73m2, p = 0.006) and high blood pressure (HBP) (− 28.4[− 46.9;-9.9] ml/min/1.73m2, p = 0.003) at ART initiation. Regarding the ART exposure in patients with normal baseline eGFR, zidovudine (AZT) with protease inhibitor (PI) (− 4.7[− 7.7;-1.6] ml/min/1.73m2, p = 0.002), tenofovir (TDF) + PI (− 13.1[− 17.4;-8.7] ml/min/1.73m2, p < 0.001), TDF without PI (− 3.2[− 5.0;-1.4] ml/min/1.73m2, p < 0.001), stavudine (d4T) + PI (− 8.5[− 14.6–2.4] ml/min/1.73m2, p = 0.006) and d4T without PI (− 5.0[− 7.6–2.4] ml/min/1.73m2, p < 0.001) were associated with poorer eGFR progression. The prevalence of CKD was 0.5% and the incidence was 1.9 [1.3; 2.7] cases/1000 person-years. The risk of CKD was higher in patients with HBP (4.3[1.8;9.9], p = 0.001), 40-49 yr. patients (4.2[1.6;11.2], p = 0.004), ≥50 yr. patients (4.5[1.5;14.1], p = 0.009) and patients exposed to abacavir (ABC) or didanosine (ddI) based ART (13.1[4.0;42.9], p < 0.001). Our findings do not confirm the high risk of CKD reported in previous studies of West Africans with HIV, but support the recommendations for early initiation of ART and close kidney function monitoring in patients with HBP or aged ≥40 yr.