Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

INTRODUCTION: Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS: We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. RESULTS: Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). CONCLUSIONS: Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.

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.

Availability of screening and treatment for common mental disorders in HIV clinic settings: data from the global International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium, 2016-2017 and 2020.

INTRODUCTION: Common mental disorders (CMDs) are highly prevalent among people with HIV. Integrating mental healthcare into HIV care may improve mental health and HIV treatment outcomes. We describe the reported availability of screening and treatment for depression, anxiety and post-traumatic stress disorder (PTSD) at global HIV treatment centres participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium in 2020 and changes in availability at sites in low- or middle-income countries (LMICs) between 2016/2017 and 2020. METHODS: In 2020, 238 sites contributing individual-level data to the IeDEA Consortium and in 2016/2017 a stratified random sample of IeDEA sites in LMICs were eligible to participate in site surveys on the availability of screening and treatment for CMDs. We assessed trends over time for 68 sites across 27 LMICs that participated in both surveys. RESULTS: Among the 238 sites eligible to participate in the 2020 site survey, 227 (95%) participated, and mental health screening and treatment data were available for 223 (98%) sites across 41 countries. A total of 95 sites across 29 LMICs completed the 2016/2017 survey. In 2020, 68% of sites were in urban settings, and 77% were in LMICs. Overall, 50%, 14% and 12% of sites reported screening with a validated instrument for depression, anxiety and PTSD, respectively. Screening plus treatment in the form of counselling was available for depression, anxiety and PTSD at 46%, 13% and 11% of sites, respectively. Screening plus treatment in the form of medication was available for depression, anxiety and PTSD at 36%, 11% and 8% of sites, respectively. Among sites that participated in both surveys, screening for depression was more commonly available in 2020 than 2016/2017 (75% vs. 59%, respectively, p = 0.048). CONCLUSIONS: Reported availability of screening for depression increased among this group of IeDEA sites in LMICs between 2016/2017 and 2020. However, substantial gaps persist in the availability of mental healthcare at HIV treatment sites across global settings, particularly in resource-constrained settings. Implementation of sustainable strategies to integrate mental health services into HIV care is needed.

Achieving consistency in measures of HIV-1 viral suppression across countries: derivation of an adjustment based on international antiretroviral treatment cohort data.

INTRODUCTION: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV-1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target. METHODS: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme. RESULTS: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010-2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.800.56 ), with uncertainty range 85.5-90.6% (0.800.70 -0.800.44 ). CONCLUSIONS: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software.

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.

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.

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.

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.

Twenty-Year Evolution of Hepatitis B Virus and Human Immunodeficiency Virus Prevalence and Incidence in Voluntary Blood Donors in Côte d'Ivoire.

BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common risk factors. The parallel description of their frequency over time may help capture their similarities and differences. METHODS: Using data from the National Transfusion Center of Abidjan, we estimated the following over a 20-year period: (1) the prevalence of HIV and hepatitis B surface antigen (HBsAg) positivity at first contact; and (2) the incidence of HIV and HBsAg seroconversion in negative first-time blood donors. RESULTS: Between 1992 and 2012, 422319 donors (men [M] = 74%) provided 1063825 blood donations. For first-time donors, HIV prevalence decreased from 7.1% (M = 5.9%, women [W] =11.0%) in 1992-1994 to 1.1% (M = 0.8%, W = 2.0%) in 2010-2012. Prevalence of HBsAg positivity remained stable at 10.8% (M = 11.7%, W = 7.3%) in 1992-1994 to 11.1% (M = 12.5%, W = 7.1%) in 2010-2012. Among regular donors (N = 129256), the incidence of becoming HIV or HBsAg positive, respectively, decreased from 4.9 per 100 (M = 4.5, W = 8.6) and 7.3 per 100 person-years (M = 7.8, W = 2.3) in 1992-1994 to 0.07 (M = 0.06, W = 0.11) and 0.2 per 100 person-years (M = 0.2, W = 0.2) in 2010-2012. CONCLUSIONS: Human immunodeficiency virus prevalence and incidence decreased dramatically over time, whereas HBV prevalence remained stable. Incidence of HBsAg seroconversion, although decreasing, still reached unexpected levels, suggesting that the risk of HBV infection in adults may be higher than expected. Hepatitis B surface antigen-negative blood-donors should be offered HBV vaccination.

Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa.

BACKGROUND: Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA. METHODS: A medical chart review was conducted in large urban HIV treatment centers in Côte d'Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen. RESULTS: Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4-14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02-4.79) had a confirmed HCV infection. CONCLUSIONS: The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012.

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.

BACKGROUND: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. METHODS: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. FINDINGS: Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per µL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3-5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9-5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1-9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39-0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. INTERPRETATION: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. FUNDING: National Research Agency on AIDS and Viral Hepatitis (ANRS).

Missed opportunities for HIV testing among newly diagnosed HIV-infected adults in Abidjan, Côte d'Ivoire.

BACKGROUND: HIV testing is crucial for starting ART earlier in HIV-infected people. We describe Missed Opportunities (MO) for HIV testing among adults newly diagnosed with HIV in Abidjan, Côte d'Ivoire. METHODS: Between april,2nd 2013 and april 1st 2014, a cross-sectional study was conducted among all adults newly diagnosed (< 1year) for HIV at the Blood Donors Medical Center of Abidjan with face to face questionnaire. An MO for HIV testing was defined as a medical consultation for a clinical indicator (e.g. symptoms, hospitalization, and pregnancy) or a non-clinical indicator (e.g. high-risk sexual behavior, HIV-infected partner) potentially related to an HIV infection but did not lead to HIV test proposal by a health care professional. RESULTS: Of the 341 patients who attended the center suring this period, 273 (157 women and 116 men) were included in this analysis. 130 (47.6%) reported at least one medical consultation for an indicator relevant for a test proposal between 1 month and five years prior to their diagnosis. Among them, 92 (77.3%) experienced at least one MO for testing. The 273 included patients reported a total of 216 indicators; 146 (67.6%) were reported without test proposal and thus were MO. Hospitalization, extreme lose of weight, chronic or repeat fever and herpes zoster were the indicators with the largest number of MO. While 66 (24.2%) patients experienced non-clinical indicators relevant to risk of HIV infection, only 11 (4.0%) mentioned it to a health professional. CONCLUSION: MO for HIV testing are frequent, even in situations for which testing is clearly recommended. Better train healthcare professionals and creating new opportunities of testing inside and, outside of medical settings are crucial to improve HIV control.

Incidence of Severe Neutropenia in HIV-Infected People Starting Antiretroviral Therapy in West Africa.

BACKGROUND: In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. METHODS: A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). RESULTS: Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6-9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8-2.6), ≥6-12 months (aHR = 2.1; 95% CI: 1.6-2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2-2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1-1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0-1.4). CONCLUSION: The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation.

New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon.

OBJECTIVE: To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon. METHODS: We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d'Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010. FINDINGS: In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/µl (interquartile range, IQR: 66 to 210) in 2007-2009 to 163 cells/µl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2). CONCLUSION: The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).

Plasma HIV-2 RNA According to CD4 Count Strata among HIV-2-Infected Adults in the IeDEA West Africa Collaboration.

BACKGROUND: Plasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve. METHOD: A cross sectional survey was conducted among HIV-2-infected individuals followed in three countries in West Africa from March to December 2012. All HIV-2 infected-patients who attended one of the participating clinics were proposed a plasma HIV-2 viral load measurement. HIV-2 RNA was quantified using the new ultrasensitive in-house real-time PCR assay with a detection threshold of 10 copies/ mL (cps/mL). RESULTS: A total of 351 HIV-2-infected individuals participated in this study, of whom 131 (37.3%) were treatment naïve and 220 (62.7%) had initiated ART. Among treatment-naïve patients, 60 (46.5%) had undetectable plasma HIV-2 viral load (<10 cps/mL), it was detectable between 10-100 cps/mL in 35.8%, between 100-1000 cps/mL in 11.7% and >1000 cps/mL in 6.0% of the patients. Most of the treatment-naïve patients (70.2%) had CD4-T cell count ≥500 cells/mm3 and 43 (46.7%) of these patients had a detectable VL (≥10 cps/mL). Among the 220 patients receiving ART, the median CD4-T cell count rose from 231 to 393 cells/mm3 (IQR [259-561]) after a median follow-up duration of 38 months and 145 (66.0%) patients had CD4-T cell count ≤ 500 cells/mm3 with a median viral load of 10 cps/mL (IQR [10-33]). Seventy five (34.0%) patients had CD4-T cell count ≥ 500 cells/mm3, among them 14 (18.7%) had a VL between 10-100 cps/mL and 2 (2.6%) had VL >100 cps/mL. CONCLUSION: This study suggests that the combination of CD4-T cell count and ultrasensitive HIV-2 viral load quantification with a threshold of 10 cps/mL, could improve ART initiation among treatment naïve HIV-2-infected patients and the monitoring of ART response among patients receiving treatment.

Severe morbidity after antiretroviral (ART) initiation: active surveillance in HIV care programs, the IeDEA West Africa collaboration.

BACKGROUND: The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities. METHODS: Within the International epidemiological Database to Evaluate AIDS (IeDEA)--West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d'Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity (death, hospitalization, fever>38°5C, Karnofsky index<70%) was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale. RESULTS: From December 2009 to December 2011, 978 adults (71% women, median age 39 years) presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study. CONCLUSIONS: This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.

Incidence of pregnancy after antiretroviral therapy initiation and associated factors in 8 West African countries.

INTRODUCTION: This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in 8 West African countries over a 10-year period. METHODS: A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged <50 years and starting ART for their own health between 1998 and 2011 were eligible. Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, hemoglobin, age, first ART regimen, and calendar year. RESULTS: Overall, 29,425 HIV-infected women aged 33 years in median (interquartile range, 28-38) contributed for 84,870 women-years of follow-up to this analysis. The crude incidence of first pregnancy (2304 events) was 2.9 per 100 women-years [95% confidence interval (CI): 2.7 to 3.0], the highest rate being reported among women aged 25-29 years: 4.7 per 100 women-years; 95% CI: 4.3 to 5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4 to 11.4) and as high as 28.4% (95% CI: 26.3 to 30.6) among women aged 20-29 years at ART initiation. CONCLUSIONS: The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world.