TDF and quantitative ultrasound bone quality in African patients on second line ART, ANRS 12169 2LADY sub-study

Abstract

BackgroundBone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality.Methods and findingsIn a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality.Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33–46 years) and median T-CD4 count was 199 cells/μl (IQR: 113–319 cells/μl). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36–72 months) and the median baseline SI was 101 (IQR: 87–116). In multivariable analysis, factors associated with baseline SI were sex (β = -10.8 [-18.1,-3.5] for women), age (β = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (β = +0.8 [0.1,1.5] per unit of BMI), and study site (β = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time.ConclusionBone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up.

Efficacy and safety of Tenofovir-based regimen in elderly people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis

“…Two of the included studies reported on some individuals with anemia. The studies showed no evidence of statistical heterogeneity ( I 2 = 0%; p > 0.05) 16, 17 . The included studies likely have a relatively small sample size (RR=1.66, 95% CI (1.02 – 2.70); I 2 = Not estimated, 2 trials, very low certainty of the evidence).…”

“…Two authors (FT and GE) independently read the titles and abstracts and excluded 92 studies because they did not meet the inclusion criteria. Four studies met the inclusion criteria as shown in Figure 1, Table 1 [14][15][16][17] . The four studies were carried out in health facilities within low-and middle-income countries.…”

“…Data were extracted from a total number of 263 persons living with HIV/AIDS receiving a tenofovir-based regimen in Lesotho, Senegal, Burkina Faso, and Cameroon. Table 2 presents the main characteristics of the 4 included studies [14][15][16][17] .…”

“…Viral suppression. The four included studies reported on viral suppression outcomes which shows that there is no significant difference between the tenofovir-based regimen and the nontenofovir-based regimen (RR = 1.96, 95% CI (1.42 -2.70); 4 trials, very low certainty of the evidence) [14][15][16][17] . (See Figure 2a)…”

“…Hypertension. A single study reported hypertension among elderly people living with HIV in sub-Saharan Africa on the TDF regimen 16 . The meta-analysis shows no observed heterogeneity for hypertension (RR = 0.76, 95% CI (0.44 -1.31), I 2 = Not estimated, 1 trial, very low certainty of evidence).…”