Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial.

Background: After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. Methods: We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. Results: Of 460 trial participants, 453 from Brazil, Côte d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/µL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB. Conclusions: We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS.

Effects of the Covid-19 pandemic on ART initiation and access to HIV viral load monitoring in adults living with HIV in West Africa: a regression discontinuity analysis.

OBJECTIVES: Efforts to control the COVID-19 pandemic have potentially compromised the availability and/or quality of HIV services. We aimed to assess the pandemic's impact on ART initiation and HIV viral load (VL) monitoring in three West African countries. METHODS: We used routinely collected data from five clinics contributing to the IeDEA collaboration in Burkina Faso, Côte d'Ivoire and Nigeria. We included ART-naïve adults living with HIV (ALWH) initiating ART from 01/01/2018. We conducted regression discontinuity analysis to estimate changes in the number of ART initiations and VL measures per week, before and during the pandemic period in each country. RESULTS: In clinics in Burkina Faso and Côte d'Ivoire, ART initiations per week remained constant throughout the studied periods (-0.24 points (p) of ART initiations/week 95%CI -5.5, 5.9, -0.9 p 95%CI -8.5,8.6, respectively), whereas in Nigeria's clinic, they decreased significantly (-6.3 p, 95% CI -10.8, -1.7) after the beginning of the pandemic. The volume of VL tests performed decreased significantly in all three countries (-17.0 p 95%CI -25.3, -8.6 in Burkina Faso, -118.4 p 95%CI -171.1, -65.8 in Côte d'Ivoire and -169.1p 95%CI-282.6, -55.6 in Nigeria). CONCLUSIONS: Access to ART was maintained for newly diagnosed ALWH despite pandemic-related physical/social distancing measures. However, VL monitoring was severely disrupted and did not return to pre-pandemic levels approximately one year after the beginning of the pandemic. While HIV services in West Africa appear rather resilient, the impact of disruptions in VL monitoring on virological and clinical outcomes should continue to be monitored.

The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America.

INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND ANALYSIS: This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA's global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.

Virologic response to antiretroviral therapy in people with HIV and tuberculosis in high tuberculosis burden countries.

OBJECTIVE: We sought to compare virologic outcomes on antiretroviral therapy (ART) between people with HIV (PWH) also treated for tuberculosis in the different countries who participated to two randomized trials. DESIGN: Pooled analysis of two randomized clinical trials. METHODS: In the phase II Reflate TB and phase III Reflate TB2 trials conducted in Brazil, Côte d'Ivoire, Mozambique and Vietnam, ART-naïve PWH treated for tuberculosis were randomized to receive raltegravir or efavirenz. We assessed country differences in baseline characteristic using Wilcoxon tests and chi-square, or Fisher's exact test. We used logistic regression to analyze determinants of virologic success, defined as week-48 plasma HIV-1 RNA <50 copies/ml. RESULTS: Of 550 participants (140 from Brazil, 170 from Côte d'Ivoire, 129 from Mozambique and 111 from Vietnam) with median baseline HIV-1 RNA of 5.4 log 10  copies/ml, 362 (65.8%) achieved virologic success at week 48. Virologic success rates were: 105/140 (75.0%) in Brazil, 99/170 (58.2%) in Côte d'Ivoire, 84/129 (65.1%) in Mozambique and 74/111 (66.7%) in Vietnam ( P  = 0.0233). Baseline HIV-1 RNA, but not the country, was independently associated with virologic success: baseline HIV-1 RNA ≥500 000 copies/ml (reference), HIV RNA <100 000 copies/ml odds ratio 3.12 [95% confidence interval (CI) 1.94; 5.01] and HIV-1 RNA 100 000-499 999 copies/ml odds ratio: 1.80 (95% CI 1.19; 2.73). Overall, 177/277 (63.9%) patients treated with raltegravir and 185/273 (67.9%) patients treated with efavirenz had a plasma HIV-1 RNA <50 copies/ml at week 48. CONCLUSIONS: Virologic response to antiretroviral therapy in PWH with TB varied across countries but was mainly driven by levels of pretreatment HIV-1 RNA.

High performance of systematic combined urine LAM test and sputum Xpert MTB/RIF® for tuberculosis screening in severely immunosuppressed ambulatory adults with HIV.

BACKGROUND: In people with HIV (PWH), the WHO-recommended tuberculosis four-symptom screen (W4SS) targeting those who need molecular rapid test may be suboptimal. We assessed the performance of different tuberculosis screening approaches in severely immunosuppressed PWH enrolled in the guided-treatment group of the STATIS trial (NCT02057796). METHODS: Ambulatory PWH with no overt evidence of tuberculosis and CD4 cell count <100/µL were screened for tuberculosis prior to antiretroviral therapy (ART) initiation with W4SS, chest X-ray, urine lipoarabinomannan (LAM) test and sputum Xpert MTB/RIF® (Xpert). Correctly and wrongly identified cases by screening approaches were assessed overall and by CD4 count threshold (≤50 and 51-99 cells/µL). RESULTS: Of 525 enrolled participants (median CD4 cell count: 28/µL), 48 (9.9%) were diagnosed with tuberculosis at enrollment. Among participants with a negative W4SS, 16% had either a positive Xpert, a chest X-ray suggestive of tuberculosis or a positive urine LAM test. The combination of sputum Xpert and urine LAM test was associated with the highest proportion of participants correctly identified as tuberculosis (95.8%) and non-tuberculosis cases (95.4%), with proportions equally high among participants with CD4 counts above or below 50 cells/µL. Restricting the use of sputum Xpert, urine LAM test or chest X-ray to participants with a positive W4SS reduced the proportion of wrongly and correctly identified cases. CONCLUSIONS: There is a clear benefit to perform both sputum Xpert and urine LAM tests as tuberculosis screening in all severely immunosuppressed PWH prior to ART initiation, and not only in those with a positive W4SS. CLINICAL TRIALS REGISTRATION: NCT02057796.

Factors associated with verbal fluency in older adults living with HIV in West Africa: A longitudinal study.

OBJECTIVE: Verbal fluency decline, observed both in aging and HIV infection, has been related to lower quality of life. This study aimed to evaluate the factors associated with categorical fluency in people living with HIV (PLHIV) aged ≥60 years living in West Africa. METHODS: In this longitudinal study, PLHIV aged ≥60 years, on antiretroviral therapy (ART) for ≥6 months were included in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. Categorical fluency was evaluated with the Isaacs Set Test at 60 s at baseline and 2 years later. Factors associated with verbal fluency baseline performance and annual rates of changes were evaluated using multivariate linear regression models. RESULTS: Ninety-seven PLHIV were included with 41 of them (42%) having a 2-year follow-up visit. The median age was 64 (62-67), 45.4% were female, and 89.7% had an undetectable viral load. The median annual change in categorical fluency scores was -0.9 (IQR: -2.7 to 1.8). Low baseline categorical fluency performance and its decline were associated with older age and being a female. Low educational level was associated with low baseline categorical fluency performance but not with its decline. Categorical fluency decline was also associated with marital status and hypertension. CONCLUSIONS: Among older West African PLHIV, usual socio-demographic variables and hypertension were the main factors associated with low categorical fluency performance and/or its decline. Interventions that focus on supporting cardiometabolic health are highly recommended to prevent cognitive disorders in PLHIV.

Determinants of Antiretroviral Treatment Success and Adherence in People With Human Immunodeficiency Virus Treated for Tuberculosis.

Background: In people with human immunodeficiency virus [HIV] presenting with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in people with HIV (PWH) treated for tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial. Methods: In this analysis, we included participants enrolled in the Reflate TB2 trial with adherence data available. The primary outcome was virologic success (HIV-1 ribonucleic acid [RNA] <50 copies/mL) at week 48, and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses. Results: Four hundred forty-four participants were included in the present analysis. Over the 48-week follow-up period, 290 of 444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288 of 444 (65%) participants were in virologic success. In the multivariate analysis, female sex (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.16-2.72; P = .0084), lower baseline HIV-1 RNA levels (<100 000; aOR, 2.29; 95% CI, 1.33-3.96; P = .0087), and pill count adherence ratio ≥95% (aOR, 2.38; 95% CI, 1.56-3.62; P < .0001) were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR, 0.81; 95% CI, .71-.92; P = .0018). Conclusions: In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence, and baseline HIV-1 RNA <100 000 copies/mL were associated with virologic success, and the number of antiretroviral tablets taken daily was a strong predictor of adherence.

Service delivery challenges in HIV care during the first year of the COVID-19 pandemic: results from a site assessment survey across the global IeDEA consortium.

INTRODUCTION: Interruptions in treatment pose risks for people with HIV (PWH) and threaten progress in ending the HIV epidemic; however, the COVID-19 pandemic's impact on HIV service delivery across diverse settings is not broadly documented. METHODS: From September 2020 to March 2021, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium surveyed 238 HIV care sites across seven geographic regions to document constraints in HIV service delivery during the first year of the pandemic and strategies for ensuring care continuity for PWH. Descriptive statistics were stratified by national HIV prevalence (<1%, 1-4.9% and ≥5%) and country income levels. RESULTS: Questions about pandemic-related consequences for HIV care were completed by 225 (95%) sites in 42 countries with low (n = 82), medium (n = 86) and high (n = 57) HIV prevalence, including low- (n = 57), lower-middle (n = 79), upper-middle (n = 39) and high- (n = 50) income countries. Most sites reported being subject to pandemic-related restrictions on travel, service provision or other operations (75%), and experiencing negative impacts (76%) on clinic operations, including decreased hours/days, reduced provider availability, clinic reconfiguration for COVID-19 services, record-keeping interruptions and suspension of partner support. Almost all sites in low-prevalence and high-income countries reported increased use of telemedicine (85% and 100%, respectively), compared with less than half of sites in high-prevalence and lower-income settings. Few sites in high-prevalence settings (2%) reported suspending antiretroviral therapy (ART) clinic services, and many reported adopting mitigation strategies to support adherence, including multi-month dispensing of ART (95%) and designating community ART pick-up points (44%). While few sites (5%) reported stockouts of first-line ART regimens, 10-11% reported stockouts of second- and third-line regimens, respectively, primarily in high-prevalence and lower-income settings. Interruptions in HIV viral load (VL) testing included suspension of testing (22%), longer turnaround times (41%) and supply/reagent stockouts (22%), but did not differ across settings. CONCLUSIONS: While many sites in high HIV prevalence settings and lower-income countries reported introducing or expanding measures to support treatment adherence and continuity of care, the COVID-19 pandemic resulted in disruptions to VL testing and ART supply chains that may negatively affect the quality of HIV care in these settings.

Ten-year attrition and antiretroviral therapy response among HIV-positive adults: a sex-based cohort analysis from eight West African countries.

INTRODUCTION: Sex differences have already been reported in sub-Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow-up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults. METHODS: We used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no-follow-up and 10-year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively. RESULTS: A total of 71,283 patients (65.8% women) contributed to 310,007 person-years of follow-up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10-year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow-up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10-year attrition throughout the 10-year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/µL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/µL in their sixth year of follow-up, whereas men failed to reach it even at the end of the 10-year follow-up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%). CONCLUSIONS: In West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex-adapted are needed for patients in care to monitor attrition, detect early high-risk groups so that they can stay in care with a durably controlled infection.

Standard dose raltegravir or efavirenz-based antiretroviral treatment for patients co-infected with HIV and tuberculosis (ANRS 12 300 Reflate TB 2): an open-label, non-inferiority, randomised, phase 3 trial.

BACKGROUND: In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug-drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz. METHODS: We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged ≥18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration <50 copies per mL). The prespecified non-inferiority margin was 12%. The primary outcome was assessed in the intention-to-treat population, which included all randomly assigned patients (excluding two patients with HIV-2 infection and one patient with HIV-1 RNA concentration of <50 copies per mL at inclusion), and the on-treatment population, which included all patients in the intention-to-treat population who initiated treatment and were continuing allocated treatment at week 48, and patients who had discontinued allocated treatment due to death or virological failure. Safety was assessed in all patients who received at least one dose of the assigned treatment regimen. This study is registered with ClinicalTrials.gov, NCT02273765. FINDINGS: Between Sept 28, 2015, and Jan 5, 2018, 460 participants were randomly assigned to raltegravir (n=230) or efavirenz (n=230), of whom 457 patients (230 patients in the raltegravir group; 227 patients in the efavirenz group) were included in the intention-to-treat analysis and 410 (206 patients in the raltegravir group; 204 patients in the efavirenz group) in the on-treatment analysis. At baseline, the median CD4 count was 103 cells per µL and median plasma HIV RNA concentration was 5·5 log10 copies per mL (IQR 5·0-5·8). 310 (68%) of 457 participants had bacteriologically-confirmed tuberculosis. In the intention-to-treat population, at week 48, 140 (61%) of 230 participants in the raltegravir group and 150 (66%) of 227 patients in the efavirenz had achieved virological suppression (between-group difference -5·2% [95% CI -14·0 to 3·6]), thus raltegravir did not meet the predefined criterion for non-inferiority. The most frequent adverse events were HIV-associated non-AIDS illnesses (eight [3%] of 229 patients in the raltegravir group; 21 [9%] of 230 patients in the efavirenz group) and AIDS-defining illnesses (ten [4%] patients in the raltegravir group; 13 [6%] patients in the efavirenz group). 58 (25%) of 229 patients in raltegravir group and 66 (29%) of 230 patients in the efavirenz group had grade 3 or 4 adverse events. 26 (6%) of 457 patients died during follow-up: 14 in the efavirenz group and 12 in the raltegravir group. INTERPRETATION: In patients with HIV given tuberculosis treatment, non-inferiority of raltegravir compared with efavirenz was not shown. Raltegravir was well tolerated and could be considered as an option, but only in selected patients. FUNDING: National French Agency for AIDS Research, Ministry of Health in Brazil, Merck. TRANSLATIONS: For the Portuguese and French translations of the abstract see Supplementary Materials section.

Barriers influencing task-shifting for the management of depression in people living with HIV: a study from West Africa IeDEA cohort collaboration.

Depression is highly prevalent in people living with HIV (PLHIV) worldwide. As mental health specialists are scarce in sub-Saharan Africa (SSA), the World Health Organization (WHO) encourages task-shifting. We aimed to evaluate the barriers that could compromise task-shifting in front-line health care workers (HCWs) who provide HIV integrated care in West Africa. We collected knowledge, attitudes and practices (KAP) information on symptoms, causes and management of depression in PLHIV in care in four clinics in Senegal and Côte d'Ivoire (N = 168). The main barriers that could compromise task-shifting came from poor knowledge, particularly on symptoms and causes. Knowledge was more limited in HCWs other than medical doctors (good answers < 70%). The access to a depression training was limited (32.7%) and was the main factor associated to poor knowledge on depression. Even when social distance and barriers to practice were low (70.8% and 69.6%, respectively), some barriers persisted. More than half of respondents considered that diagnosis and management needed to be performed by a specialist. To guarantee the success of task-shifting, in the perspective of integrated care, efforts are needed to improve the access to specific training on depression considering screening, management, but also perceptions and attitudes, as some barriers subsist.

Childbearing desire and reproductive behaviors among women living with HIV: A cross-sectional study in Abidjan, Côte d'Ivoire.

INTRODUCTION: Evidence on childbearing desire and reproductive behaviors in women living with HIV on antiretroviral therapy (ART) is scarce, particularly in West Africa. We investigated the prevalence and associated factors of childbearing desire in HIV-infected women in care in Abidjan, Côte d'Ivoire and explored whether such desires were translated into behaviors related to contraceptive use and communication with health personnel. METHODS: A cross-sectional survey was conducted in two HIV-care facilities in Abidjan, Côte d'Ivoire in 2015. Eligible women were non-pregnant, non-menopausal, aged 18-49 years and diagnosed as HIV-infected. The outcomes were childbearing desire, prevalence of modern contraceptive use, unmet needs for family planning and intention of the last pregnancy since HIV diagnosis. Women wishing to conceive immediately were asked whether they had discussed their desire with HIV healthcare workers. Logistic regression models were used to assess the associations between the outcomes and women's characteristics. RESULTS: Of 1,631 women, 80% declared having childbearing desire. No association was found between women's childbearing desire and ART status or its duration. In multivariate models, younger age, being in a stable relationship and having no or only one child were significantly associated with increased childbearing desire. Of the women wishing to conceive immediately (n = 713), only 43% reported having had fertility-related dialogue with healthcare provider. Among sexually active women wanting to avoid or delay pregnancy (n = 650), unmet needs for family planning was 40%. Regarding the last pregnancy since HIV diagnosis, one in three women reported not having wanted a baby at that time. CONCLUSIONS: Pregnancy desire in women living with HIV in Abidjan was extremely high. Integration of safe conception strategies as well as improvement of contraceptive uptake among women in need of family planning are of utmost importance to ensure optimal conception and to avoid transmission of HIV to the male partner or to the forthcoming child.

Prevalence and factors associated with physical function limitation in older West African people living with HIV.

Although physical function decline is common with aging, the burden of this impairment remains underestimated in patients living with HIV (PLHIV), particularly in the older people receiving antiretroviral treatment (ART) and living in sub-Saharan Africa (SSA). PLHIV aged ≥50 years old and on ART since ≥6 months were included (N = 333) from three clinics (two in Côte d'Ivoire, one in Senegal) participating in the International epidemiological Databases to Evaluate AIDS (IeDEA) West Africa collaboration. Physical function was measured using the Short Physical Performance Battery (SPPB), the unipodal balance test and self-reported questionnaires. Grip strength was also assessed. Logistic regression was used to identify the factors associated with SPPB performance specifically. Median age was 57 (54-61) years, 57.7% were female and 82.7% had an undetectable viral load. The mean SPPB score was 10.2 ±1.8. Almost 30% had low SPPB performance with the 5-sit-to-stand test being the most altered subtest (64%). PLHIV with low SPPB performance also had significantly low performance on the unipodal balance test (54.2%, p = 0.001) and low mean grip strength (but only in men (p = 0.005)). They also showed some difficulties in daily life activities (climbing stairs, walking one block, both p<0.0001). Age ≥60 years (adjusted OR (aOR) = 3.4; CI95% = 1.9-5.9,), being a female (aOR = 2.1; CI95% = 1.1-4.1), having an abdominal obesity (aOR = 2.1; CI95% = 1.2-4.0), a longer duration of HIV infection (aOR = 2.9; CI95% = 1.5-5.7), old Nucleoside reverse transcriptase inhibitors (NRTIs) (i.e., AZT: zidovudine, ddI: didanosine, DDC: zalcitabine, D4T: stavudine) in current ART (aOR = 2.0 CI95% = 1.1-3.7) were associated with low SPPB performance. As in western countries, physical function limitation is now part of the burden of HIV disease complications of older PLHIV living in West Africa, putting this population at risk for disability. How to screen those impairments and integrate their management in the standards of care should be investigated, and specific research on developing adapted daily physical activity program might be conducted.

Prevalence and factors associated with severe depressive symptoms in older west African people living with HIV.

BACKGROUND: Depression is one of the most common psychiatric disorders in people living with HIV (PLHIV). Depression has a negative impact on both mental and physical health and is mainly associated with suboptimal HIV treatment outcomes. To encourage successful aging and the achievement of the 3 × 90 objectives in older PLHIV, the psychological domain must not be neglected. In this context and as data are scarce in West Africa, this study aimed to evaluate the prevalence and the factors associated with severe depressive symptoms in older PLHIV living in this region of the world. METHODS: Data from PLHIV aged ≥50 years and on ART since ≥6 months were collected in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. The severity of depressive symptoms was measured using the Center for Epidemiological Studies Depression scale (CES-D), and associated factors were identified using logistic regressions. RESULTS: The median age of the 334 PLHIV included in the study was 56.7 (53.5-61.1), 57.8% were female, and 87.1% had an undetectable viral load. The prevalence of severe depressive symptoms was 17.9% [95% Confidence Interval (95% CI): 13.8-22.0]. PLHIV with severe depressive symptoms were more likely to be unemployed (adjusted Odd Ratio (aOR) = 2.8; 95% CI: 1.4-5.7), and to be current or former tobacco smokers (aOR = 2.6; 95% CI: 1.3-5.4) but were less likely to be overweight or obese (aOR = 0.4; 95% CI: 0.2-0.8). CONCLUSIONS: The prevalence of severe depressive symptoms is high among older PLHIV living in West Africa. Unemployed PLHIV and tobacco smokers should be seen as vulnerable and in need of additional support. Further studies are needed to describe in more details the reality of the aging experience for PLHIV living in SSA. The integration of screening and management of depression in the standard of care of PLHIV is crucial.

Incidence of Tuberculosis During the First Year of Antiretroviral Treatment in West African HIV-Infected Adults.

We estimated tuberculosis incidence during the first year on antriretroviral therapy without isoniazid-preventive treatment in 6938 West African HIV-infected adults at 3.33 cases per 100 person-years (95% CI, 2.85-3.80). In multivariate Poisson models, sites in Cote d'Ivoire, male gender, low body mass index, low hemoglobin, low CD4 count, and young age were significantly associated with higher incidence.

Systematic or Test-Guided Treatment for Tuberculosis in HIV-Infected Adults.

BACKGROUND: In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. METHODS: We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. RESULTS: A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. CONCLUSIONS: Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events. (Funded by the Agence Nationale de Recherches sur le Sida et les Hépatites Virales; STATIS ANRS 12290 ClinicalTrials.gov number, NCT02057796.).

Mortality Among People With HIV Treated for Tuberculosis Based on Positive, Negative, or No Bacteriologic Test Results for Tuberculosis: The IeDEA Consortium.

BACKGROUND: In resource-constrained settings, many people with HIV (PWH) are treated for tuberculosis (TB) without bacteriologic testing. Their mortality compared with those with bacteriologic testing is uncertain. METHODS: We conducted an observational cohort study among PWH ≥15 years of age initiating TB treatment at sites affiliated with 4 International epidemiology Databases to Evaluate AIDS consortium regions from 2012 to 2014: Caribbean, Central and South America, and Central, East, and West Africa. The exposure of interest was the TB bacteriologic test status at TB treatment initiation: positive, negative, or no test result. The hazard of death in the 12 months after TB treatment initiation was estimated using a Cox proportional hazard model. Missing covariate values were multiply imputed. RESULTS: In 2091 PWH, median age 36 years, 53% had CD4 counts ≤200 cells/mm3, and 52% were on antiretroviral therapy (ART) at TB treatment initiation. The adjusted hazard of death was higher in patients with no test compared with those with positive test results (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.08-2.26). The hazard of death was also higher among those with negative compared with positive tests but was not statistically significant (HR, 1.28; 95% CI, 0.91-1.81). Being on ART, having a higher CD4 count, and tertiary facility level were associated with a lower hazard for death. CONCLUSIONS: There was some evidence that PWH treated for TB with no bacteriologic test results were at higher risk of death than those with positive tests. Research is needed to understand the causes of death in PWH treated for TB without bacteriologic testing.

Exploring the Patterns of Use and Acceptability of Mobile Phones Among People Living With HIV to Improve Care and Treatment: Cross-Sectional Study in Three Francophone West African Countries.

BACKGROUND: The use of mobile technology in health care (mobile health [mHealth]) could be an innovative way to improve health care, especially for increasing retention in HIV care and adherence to treatment. However, there is a scarcity of studies on mHealth among people living with HIV (PLHIV) in West and Central Africa. OBJECTIVE: The aim of this study was to assess the acceptability of an mHealth intervention among PLHIV in three countries of West Africa. METHODS: A cross-sectional study among PLHIV was conducted in 2017 in three francophone West African countries: Côte d'Ivoire, Burkina Faso, and Togo. PLHIV followed in the six preselected HIV treatment and care centers, completed a standardized questionnaire on mobile phone possession, acceptability of mobile phone for HIV care and treatment, preference of mobile phone services, and phone sharing. Descriptive statistics and logistic regression were used to describe variables and assess factors associated with mHealth acceptability. RESULTS: A total of 1131 PLHIV-643 from Côte d'Ivoire, 239 from Togo, and 249 from Burkina Faso-participated in the study. Median age was 44 years, and 76.1% were women (n=861). Almost all participants owned a mobile phone (n=1107, 97.9%), and 12.6% (n=140) shared phones with a third party. Acceptability of mHealth was 98.8%, with the majority indicating their preference for both phone calls and text messages. Factors associated with mHealth acceptability were having a primary school education or no education (adjusted odds ratio=7.15, 95% CI 5.05-10.12; P<.001) and waiting over one hour before meeting a medical doctor on appointment day (adjusted odds ratio=1.84, 95% CI 1.30-2.62; P=.01). CONCLUSIONS: The use of mHealth in HIV treatment and care is highly acceptable among PLHIV and should be considered a viable tool to allow West and Central African countries to achieve the Joint United Nations Programme on HIV/AIDS 90-90-90 goals.

Implementation of an intensive adherence intervention in patients with second-line antiretroviral therapy failure in four west African countries with little access to genotypic resistance testing: a prospective cohort study.

BACKGROUND: The decision about whether to switch to third-line antiretroviral therapy (ART) in patients with treatment failure on second-line therapy is difficult in settings with little access to genotypic resistance testing. In this study, we used a standardised algorithm including a wide range of adherence-enhancing interventions followed by a new viral load measurement to decide whether to switch to third-line therapy in this situation. The decision, made on the basis of effectiveness of the adherence reinforcement to drive viral resuppression, did not use genotypic resistance testing. METHODS: In this prospective cohort study, adults in four west African countries with treatment failure of a boosted protease inhibitor ART regimen were offered nine adherence reinforcement interventions, and followed up for 64 weeks. We measured viral load at week 12 and used the results to decide ART treatment at week 16: if successful resuppression (plasma HIV-1 RNA <400 copies per mL or had decreased by ≥2 log10 copies per mL compared with baseline), patients continued the same second-line regimen; otherwise they switched to a third-line regimen based on ritonavir-boosted darunavir and raltegravir. The primary endpoint was virological success at week 64 (plasma HIV-1 RNA <50 copies per mL). After study termination we did genotypic resistance testing on frozen plasma samples collected at baseline, and retrospectively determined the appropriateness of the week 16 decision on the basis of the baseline genotypic susceptibility score. FINDINGS: Between March 28, 2013, and May 11, 2015, of the 198 eligible participants, five died before week 16. Of the 193 remaining, 130 (67%) reached viral resuppression and continued with second-line ART, and 63 (33%) switched to third-line ART at week 16. Post-study genotypic resistance testing showed that the baseline genotypic susceptibility score was calculable in 166 patients, of whom 57 (34%) had a score less than 2. We retrospectively concluded that the week 16 decision was appropriate in 145 (75%) patients. At week 64, four patients (2%) were lost to follow-up, ten (5%) had died, and 101 (52%) had a viral load less than 50 copies per mL. INTERPRETATION: Poor adherence is the first problem to tackle in patients for whom second-line ART is failing when resistance tests are not routinely available and is effectively a manageable problem. Lack of access to genotypic resistance testing should not be an obstacle to the prescription of third-line ART in patients who do not achieve viral resuppression after adherence reinforcement. FUNDING: French Agency for Research on AIDS and Viral Hepatitis.

Assessment of the scale-up of cervical cancer screening in Abidjan stratified by HIV status.

OBJECTIVE: To report the successes and challenges of scaling up a population-based cervical cancer (CC) screening program from HIV clinics to various healthcare facilities in Abidjan, Côte d'Ivoire. METHOD: A retrospective analysis of characteristics, outcomes, and follow-up of women attending an initial CC screening visit in Abidjan between January 2010 and December 2014. Data were collected via forms that were systematically completed during CC screening visits. Data from the 2014 population census were used to estimate screening coverage. RESULTS: Among 16 169 women attending an initial CC screening, 1616 (10.0%) had a positive VIA test. Among 848 women eligible for immediate cryotherapy, 618 (72.9%) underwent the "see-and-treat" approach. The 1-year follow-up rate after cryotherapy was 23.1% (143/618), and was higher among women with HIV (111/362, 30.7%) than among other women (32/256, 12.5%) (P=0.001). The estimated coverage of CC screening in Abidjan was 1.2% (95% confidence interval, 0.6-3.1). CONCLUSION: Despite successful expansion of CC screening from HIV clinics to other facilities, the estimated screening coverage of the targeted population remained low. Follow-up of positively screened and treated women is a major challenge, especially outside HIV clinics, and would benefit from an innovative information system proving unique identification and tracking systems.