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Objectives: We report the association between pre‐antiretroviral therapy (pre‐ART) soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels and long‐term mortality in HIV‐infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial). Methods: The ART‐naïve HIV‐infected adults were randomly assigned to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the trial follow‐up were invited to participate in a post‐trial phase (PTP). The PTP end‐point was all‐cause death. We used multivariable Cox proportional models to analyse the association between baseline sVCAM‐1 and all‐cause death, adjusting for ART strategy, sex, CD4 count, plasma HIV‐1 RNA and peripheral blood mononuclear cell HIV‐1 DNA levels. Results: In all, 954 adults (77% women, median CD4 count of 387 cells/μL) were randomly assigned to start ART immediately (n = 477) or to defer initiation of ART (n = 477). They were followed for a median of 5.8 years [interquartile range (IQR): 5.2–6.3]. In multivariable analysis, the risk of death was significantly associated with baseline sVCAM‐1 [≥1458 vs. < 1458 ng/mL; adjusted hazard ratio = 2.86, 95% confidence interval (CI): 1.60–5.11]. The 6‐year probability of death rates were 14.4% (95%CI: 9.1–22.6) and 9.4% (5.4–16.1) in patients with baseline sVCAM‐1 ≥ 1458 ng/mL randomized to deferred and immediate ART, respectively, and 3.8% (2.2–6.5) and 3.5% (1.9–6.3) in patients with baseline sVCAM‐1 < 1458 ng/mL randomized to deferred and immediate ART. The median difference between pre‐ART and 12‐month sVCAM‐1 levels in patients randomized to immediate ART was −252 (IQR: −587 to −61). Conclusions: Pre‐ART sVCAM‐1 levels were significantly associated with mortality, independently of whether ART was started immediately or deferred, but they significantly decreased after 12 months of ART. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance.Methods: In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30 months. Those in the deferred group who started ART were monitored for longer, until they had completed 30 months on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30 months after ART initiation.Results: Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465 cells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10 copies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, P = 0.04) and a lower genotypic susceptibility score (P = 0.04).Conclusions: Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited. [ABSTRACT FROM AUTHOR]

It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir‐based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub‐Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)‐positive with HBV DNA ≥ 2,000 IU/ml; HBsAg‐positive with HBV DNA < 2,000 IU/ml; isolated HBcAb‐positive; resolved infection (HBsAb‐positive/HBcAb‐positive); and HBV non‐immune/vaccinated (HBcAb‐negative). We compared square‐root CD4‐cell count increases using mixed‐effect, non‐linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all‐cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti‐HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non‐immune/vaccinated. We found no significant difference in CD4 cell increases between HBV‐infection groups after adjustment (p = 0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all‐cause mortality (1.9/100 person‐years, 95% Credibile Interval [CrI] = 1.0–3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI = −79%, −13%), 60% (95%CrI = −82%, −12%) and 66% (95%CrI = −84%, −23%) in those who had isolated anti‐HBcAb‐positive, resolved HBV infection and HBV non‐immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti‐HBcAb‐positive serology, much like HBV non‐immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV‐related management would not be necessary for these individuals. [ABSTRACT FROM AUTHOR]

Context: Data on cardiovascular risk (CVR) score among HIV-infected patients in sub-Saharan Africa are scarce. Our first objective was to compare the CVR score of Framingham utilizing BMI and lipids at baseline, and secondary to assess evolution of CVR score over time at Month 30 in the Temprano trial. Methods: HIV-infected adults with CD4 <800/mm3 without criteria for initiating ART were included and followed for 30 months in the Temprano trial, which assessed the benefits and risks of early antiretroviral treatment (ART) vs deferred ART. CVR score was estimated at baseline and Month-30 using Framingham equations with either BMI or lipids and classified as high (>20%), moderate (10–20%), and low risk (<10%). At baseline, we compare these two estimations utilizing the Pearson correlation test and analyze the increasing CV risk score over time by Proportional odds cumulative logit models for people attending the Month-30 (M30) visit. Results: Among the 2056 patients, 78% were women, median age was 35 years, and median CD4 count was 464/mm3, 6.8% were obese, 6.3% had hypertension, 7.8% were smokers (1.8% women, 26.8% men), 19% had Total Cholesterol (TC) >5mmol/L, and 1% diabetes at baseline. At baseline the concordance between the two Framingham equations was excellent (r = 0.95; p<0.0001). Among the 1700 patients who attended M30 visit and with available data, 1.3% had a high CV risk score at baseline and 3.1% at M30 visit using Framingham equation with BMI. Adjusted odds ratio (aOR) of being at a higher CV risk score at M30 visit compared to a higher CV risk score at M0 visit was 1.35 (CI 95% 1.17–1.57). Stratified by sex, the increasing CV risk score was OR 1.73 (CI 95%: 1.30–2.29) for women and OR 1.24 (CI 95%: 1.02–1.50) for men. Early ART was not associated with an increasing CV risk score (p = 0.88). Results for the 1422 patients with Framingham equation using lipids were similar. Conclusion: In a large trial evaluating early ART for HIV infection in Côte d’Ivoire, Framingham equation with BMI and lipids were highly correlated and CV risk score increases over time. Early ART was not significantly associated with this increasing CV risk score. [ABSTRACT FROM AUTHOR]

Background. Optimal laboratory monitoring of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) remains controversial. We evaluated current and novel monitoring strategies in Côte d'Ivoire, West Africa. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications -International model to compare clinical outcomes, cost-effectiveness, and budget impact of 11 ART monitoring strategies varying by type (CD4 and/or viral load [VL]) and frequency. We included "adaptive" strategies (biannual then annual monitoring for patients on ART/suppressed). Mean CD4 count at ART initiation was 154/μL. Laboratory test costs were CD4=$11 and VL=$33. The standard of care (SOC; biannual CD4) was the comparator. We assessed cost-effectiveness relative to Côte d'Ivoire's 2013 per capita GDP ($1500). Results. Discounted life expectancy was 16.69 years for SOC, 16.97 years with VL confirmation of immunologic failure, and 17.25 years for adaptive VL. Mean time on failed first-line ART was 3.7 years for SOC and <0.9 years for all routine/adaptive VL strategies. VL failure confirmation was cost-saving compared with SOC. Adaptive VL had an incremental cost-effectiveness ratio (ICER) of $4100/year of life saved compared with VL confirmation and increased the 5-year budget by $310/patient compared with SOC. Adaptive VL achieved an ICER <1× GDP if second-line ART and VL costs simultaneously decreased to $156 and $13, respectively. Conclusions. VL confirmation of immunologic failure is more effective and less costly than CD4 monitoring in Côte d'Ivoire. Adaptive VL monitoring reduces time on failing ART, is cost-effective, and should become standard in Côte d'Ivoire and similar settings. [ABSTRACT FROM AUTHOR]

Background: HIV is usually associated with weight loss. World health Organization (WHO) recommends early antiretroviral (ART) initiation, but data on the progression of body mass index (BMI) in participants initiating early ART in Africa are scarce. Methods: The Temprano randomized trial was conducted in Abidjan to assess the effectiveness of early ART and Isoniazid (INH) prophylaxis for tuberculosis in HIV-infected persons with high CD4 counts below 800 cells/mm3 without any indication for starting ART. Patients initiating early ART before December 2010 were included in this sub-study. BMI was categorized as: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). At baseline and after 24 months of ART, prevalence of being overweight or obese and factors associated with being overweight or obese were estimated using univariate and multivariate logistic regression. Results: At baseline, 755 participants (78 % women; median CD4 count 442/mm3, median baseline BMI 22 kg/m2) initiated ART. Among them, 19.7 % were overweight, and 7.2 % were obese at baseline. Factors associated with being overweight or obese were: female sex aOR 2.3 (95 % CI 1.4-3.7), age, aOR for 5 years 1.01 (95 % CI 1.0-1.2), high living conditions aOR 2.6 (95 % CI 1.5-4.4), High blood pressure aOR 4.3 (95 % CI 2.0-9.2), WHO stage 2vs1 aOR 0.7 (95 % CI 0.4-1.0) and Hemoglobin ≥95 g/dl aOR 3.0 (95 % CI 1.6-5.8). Among the 597 patients who attended the M24 visit, being overweight or obese increased from 20.4 to 24.8 % (p = 0.01) and 7.2 to 9.2 % (p = 0.03) respectively and factor associated with being overweight or obese was immunological response measured as an increase of CD4 cell count between M0-M24 (for +50 cells/mm3: aOR 1.01; 95 % CI 1.05-1.13, p = 0.01). Conclusion: The weight categories overweight and obese are highly prevalent in HIV-infected persons with high CD4 cell counts at baseline, and increased over 24 months on ART in this Sub-Saharan African population. [ABSTRACT FROM AUTHOR]

Background. The effect of early initiation of antiretroviral therapy (ART; ie, at CD4+ T-cell counts >350 cells/mm3) on sexual behaviors and human immunodeficiency virus type 1 (HIV) transmission risk has not been documented in populations other than HIV-serodiscordant couples in stable relationships.Methods. On the basis of data from a behavioral study nested in a randomized, controlled trial (Temprano-ANRS12136) of early ART, we compared proportions of risky sex (ie, unprotected sex with a partner of negative/unknown HIV status) reported 12 months after inclusion between participants randomly assigned to initiate ART immediately (hereafter, “early ART”) or according to ongoing World Health Organization criteria. Group-specific HIV transmission rates were estimated on the basis of sexual behaviors and viral load–specific per-act HIV transmission probabilities. The ratio of transmission rates was computed to estimate the protective effect of early ART.Results. Among 957 participants (baseline median CD4+ T-cell count, 478 cells/mm3), 46.0% reported sexual activity in the past month; of these 46.0%, sexual activity for 41.5% involved noncohabiting partners. The proportion of subjects who engaged in risky sex was 10.0% in the early ART group, compared with 12.8% in the standard ART group (P = .17). After accounting for sexual behaviors and viral load, we estimated that the protective effect of early ART was 90% (95% confidence interval, 81%–95%).Conclusion. Twelve months after inclusion, patients in the early and standard ART groups reported similar sexual behaviors. Early ART decreased the estimated risk of HIV transmission by 90%, suggesting a major prevention benefit among seronegative sex partners in stable or casual relationships with seropositive individuals. [ABSTRACT FROM PUBLISHER]

Background. A randomized trial was launched in Côte d'Ivoire in 2002 to compare continuous antiretroviral treatment (hereafter, "C-ART") to an ART regimen of 2 months off and 4 months on therapy (hereafter, "2/4-ART"). We report the final analysis. Methods. A total of 435 adults who were receiving successful ART ((median CD4 cell count prior to ART, 272 cells/mm3; 88% were receiving a zidovudine-lamivudine-efavirenz regimen) were randomized to receive C-ART or 2/4-ART. The main primary end point was the percentage of patients with <350 CD4 cells/mm3 at 24 months. The sample size ensured 80% power to demonstrate noninferiority (noninferiority bound, -15%), assuming that 30% of the patients in the C-ART arm would have <350 CD4 cells/mm3. Other end points were mortality, morbidity, cost of care, genotypic resistance, adherence, and toxicity. Results. The percentage of patients with <350 CD4 cells/mm3 at 24 months was 5.6% (6 of 107) in the C-ART arm and 14.6% (46 of 315) in the 2/4-ART arm (lower bound of the 95% CI for the difference, -14%). Cost was 18% higher in the C-ART arm, and resistance to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was 20% higher in the 2/4-ART arm. Other end points were nonconclusive. Conclusions. Although 2/4-ART met the predetermined criteria for noninferiority, the percentage of patients with <350 CD4 cells/mm3 in the C-ART arm was lower than anticipated, which makes the clinical significance of this noninferiority uncertain. In addition, 2/4-ART led to an unacceptable additional risk of selecting for drug-resistant virus. This new argument against episodic ART strategies is also a caveat against any unplanned ART interruptions in Africa, where most patients receive NNRTIs. [ABSTRACT FROM AUTHOR]

Summary 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 mm, 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 mm) 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 mm. 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 mm. This CD4-guided structured treatment interruption strategy should not be recommended in Abidjan. [ABSTRACT FROM AUTHOR]

The article focuses on the study of the highly active antiretroviral therapy of HIV patients in Sub-Saharan Africa. The study highlighted the significance of efavirenz from seven hundred forty patients. It was revealed that only .8 percent of patients have permanently discontinued the use efavirenz for severe side effects particularly on pregnant women. Efavirenz could be considered a valuable first-line nonnucleoside reverse transcriptase inhibitor but considers close monitoring for risks.

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/m2 (interquartile range, IQR: 0.0-2.1), the median change in CD4 an increase of 148/μl (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/m2 versus 0.99 kg/m2, 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. [ABSTRACT FROM AUTHOR]