Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

OBJECTIVE: We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART adherence and viral load (VL) and therefore sought to examine these associations. METHODS: The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL [(<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed)]. RESULTS: Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz [32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001]. Compared with a TBW change <5% [950 (63.0%) participants], TBW gain ≥5% was not significantly associated with more days with missed ART doses [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23] or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16). CONCLUSIONS: Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.

Assessing the impact of HIV support groups on antiretroviral therapy adherence and viral suppression in the African cohort study.

BACKGROUND: Support groups for people living with HIV (PLWH) may improve HIV care adherence and outcomes. We assessed the impact of support group attendance on antiretroviral therapy (ART) adherence and viral suppression in four African countries. METHODS: The ongoing African Cohort Study (AFRICOS) enrolls participants at 12 clinics in Kenya, Uganda, Tanzania, and Nigeria. Self-reported attendance of any support group meetings, self-reported ART adherence, and HIV RNA are assessed every 6 months. Logistic regression models with generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for support group attendance and other factors potentially associated with ART adherence and viral suppression. RESULTS: From January 2013 to December 1, 2019, 1959 ART-experienced PLWH were enrolled and 320 (16.3%) reported any support group attendance prior to enrollment. Complete ART adherence, with no missed doses in the last 30 days, was reported by 87.8% while 92.4% had viral suppression <1000copies/mL across all available visits. There was no association between support group attendance and ART adherence in unadjusted (OR 1.01, 95% CI 0.99-1.03) or adjusted analyses (aOR 1.00, 95% CI 0.98-1.02). Compared to PLWH who did not report support group attendance, those who did had similar odds of viral suppression in unadjusted (OR 0.99, 95% CI 0.978-1.01) and adjusted analyses (aOR 0.99, 95% CI 0.97-1.01). CONCLUSION: Support group attendance was not associated with significantly improved ART adherence or viral suppression, although low support group uptake may have limited our ability to detect a statistically significant impact.

Persons living with HIV in sero-discordant partnerships experience improved HIV care engagement compared with persons living with HIV in sero-concordant partnerships: a cross-sectional analysis of four African countries.

BACKGROUND: Persons living with HIV (PLWH) who are members of sero-discordant and sero-concordant relationships may experience psychological stressors or motivators that affect HIV care. We assessed the association between sero-discordance status, antiretroviral therapy (ART) uptake, and viral suppression in the African Cohort Study (AFRICOS). METHODS: AFRICOS enrolls PLWH and HIV-uninfected individuals at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, we determined ART use through self-report. Viral suppression was defined as HIV RNA < 1000 copies/mL. We analyzed PLWH who were index participants within two types of sexual dyads: sero-discordant or sero-concordant. Binomial regression models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ART use and viral suppression at study enrollment. RESULTS: From January 2013 through March 2018, 223 index participants from sero-discordant dyads and 61 from sero-concordant dyads were enrolled. The majority of the indexes were aged 25-34 years (50.2%), female (53.4%), and married (96.5%). Sero-discordant indexes were more likely to disclose their status to partners compared with sero-concordant indexes (96.4% vs. 82.0%, p < 0.001). After adjustment, sero-discordant index participants were more likely to be on ART (aPR 2.8 [95% CI 1.1-6.8]), but no more likely to be virally suppressed. Results may be driven by unique psycho-social factors and global implementation of treatment as prevention. CONCLUSIONS: PLWH in sero-discordant sexual partnerships demonstrated improved uptake of ART compared with those in sero-concordant partnerships. Interventions are needed to increase care engagement by individuals in sero-concordant relationships to improve HIV outcomes.

The pregnancy factor: the prevalence of depression among women living with HIV enrolled in the African Cohort Study (AFRICOS) by pregnancy status.

Among Sub-Saharan African women living with HIV (WLWH), pregnancy creates unique stressors that may cause depression. We describe the prevalence of depression among WLWH enrolled in the African Cohort Study (AFRICOS) by pregnancy status and describe factors associated with depression. WLWH < 45 years of age underwent six-monthly visits with depression diagnosed using the Center for Epidemiological Studies-Depression scale. Visits were categorized as "pregnant;" "postpartum" (the first visit made after the last pregnancy visit), and "non-pregnant." The prevalence of depression was calculated for each visit type and compared using prevalence odds ratios (POR) with 95% confidence intervals (CI). Logistic regression with generalized estimating equations was used to evaluate sociodemographic factors associated with depression. From January 2013 to March 1, 2020, 1333 WLWH were enrolled, and 214 had pregnancies during follow-up. As compared to the prevalence of depression during "non-pregnant" visits (9.1%), depression was less common at "pregnant" (6.3%; POR = 0.68 [CI: 0.42, 1.09]) and "postpartum" (3.4%; POR = 0.36 [CI: 0.17, 0.76]) visits. When controlling for other factors, the visit category was not independently associated with depression. Visit number, study site, employment status, and food security were independently associated with decreased odds of depression. We observed a lower prevalence of depression during pregnancy and the postpartum period than has been previously described among WLWH during similar time points. We observed protective factors against depression which highlight the impact that holistic and consistent health care at HIV-centered clinics may have on the well-being of WLWH in AFRICOS.

Noninfectious Comorbidity in the African Cohort Study.

BACKGROUND: Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)-infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. METHODS: At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. RESULTS: Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22-1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27-1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13-1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06-1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. CONCLUSIONS: HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART.

Advanced HIV disease in East Africa and Nigeria, in The African Cohort Study.

BACKGROUND: Earlier antiretroviral therapy (ART) may decrease progression to advanced HIV disease (AHD) with CD4 count of <200 cells per cubic millimeter or clinical sequelae. We assessed factors associated with AHD among people living with HIV before and during the "test and treat" era. SETTING: The African Cohort Study prospectively enrolls adults with and without HIV from 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. METHODS: Enrollment evaluations included clinical history, physical examination, and laboratory testing. Generalized estimating equations were used to estimate adjusted odds ratios and 95% confidence intervals for factors associated with CD4 count of <200 cells per cubic millimeter at study visits. RESULTS: From 2013 to 2021, 3059 people living with HIV with available CD4 at enrollment were included; median age was 38 years [interquartile range: 30-46 years], and 41.3% were men. From 2013 to 2021, the prevalence of CD4 count of <200 cells per cubic millimeter decreased from 10.5% to 3.1%, whereas the percentage on ART increased from 76.6% to 100% ( P <0.001). Factors associated with higher odds of CD4 count of <200 cells per cubic millimeter were male sex (adjusted odds ratio 1.56 [confidence interval: 1.29 to 1.89]), being 30-39 years (1.42 [1.11-1.82]) or older (compared with <30), have World Health Organization stage 2 disease (1.91 [1.48-2.49]) or higher (compared with stage 1), and HIV diagnosis eras 2013-2015 (2.19 [1.42-3.37]) or later (compared with <2006). Compared with ART-naive, unsuppressed participants, being viral load suppressed on ART, regardless of ART duration, was associated with lower odds of CD4 count of <200 cells per cubic millimeter (<6 months on ART: 0.45 [0.34-0.58]). CONCLUSION: With ART scale-up, AHD has declined. Efforts targeting timely initiation of suppressive ART may further reduce AHD risk.

Cumulative exposure to depressive symptoms and all-cause mortality among adults with HIV in Kenya, Nigeria, Tanzania, and Uganda.

OBJECTIVE: We estimated the effects of cumulative exposure to depressive symptoms on risk of all-cause mortality among people with HIV (PWH) in four African countries. DESIGN: An analysis of prospective cohort data. METHODS: The African Cohort Study (AFRICOS) is a prospective cohort of people receiving care at twelve clinics in Kenya, Nigeria, Tanzania, and Uganda. Every 6 months from January 2013 to May 2020, participants underwent laboratory monitoring, structured surveys, and assessment of depressive symptom severity using the Center for Epidemiologic Studies Depression Scale (CES-D). All-cause mortality was the outcome of interest. The predictor of interest was a time-updated measure of the percentage of days lived with depression (PDD). Marginal structural Cox proportional hazards regression models were used, adjusting for potential confounders including time-varying alcohol use, drug use, and viral load. RESULTS: Among 2520 enrolled participants, 1479 (59%) were women and the median age was 38 (interquartile range [IQR]: 32-46). At enrollment, 1438 (57%) were virally suppressed (<200 copies/ml) and 457 (18%) had CES-D at least 16, indicating possible depression. Across 9093 observed person-years, the median PDD was 0.7% (IQR: 0-5.9%) with 0.8 deaths per 100 person-years. Leading causes of death included cancer (18% of deaths) and accidents (14%). Models suggested that each 25% absolute increase in PDD was associated with a 69% increase in the risk of all-cause mortality (hazard ratio: 1.69; 95% confidence interval: 1.18-2.43). CONCLUSION: Cumulative exposure to depressive symptoms was substantially associated with the risk of mortality in this cohort of PWH in Africa.

High hepatitis B vaccination coverage among a cohort of predominantly men who have sex with men in Germany.

Incidence of hepatitis B virus (HBV) infection has declined dramatically since the introduction of the HBV vaccine, but gaps remain in coverage. We characterized factors associated with vaccination among individuals with sexual risk of HBV infection. The BRAHMS observational cohort enrolled men and transgender women, without HIV, aged 18-55 years, with behavioral vulnerability to sexually transmitted infections at 10 German outpatient clinics. HBV surface antigen, surface antibody, and core antibody were assessed at screening for cohort eligibility to determine HBV vaccination status. Modified Poisson regression with robust standard errors was used to calculate adjusted prevalence ratios (aPR) and 95% confidence intervals (95% CI) for factors potentially associated with prior HBV vaccination. A total of 1,042 participants were included in these cross-sectional analyses, with 831 participants (79.7%) immune to HBV due to vaccination. Knowledge around HBV vaccination recommendations (aPR: 0.87; 95% CI: 0.78-0.98). and age (aPR 40-49 vs 18-29 years: 0.88; 95% CI: 0.79-0.97) were significantly associated with a history of HBV vaccination in both the unadjusted and adjusted models. Education about the availability of vaccines and recommendations for vaccinations may improve coverage.

Preparing for future European efficacy trials of interventions to prevent HIV and other sexually transmitted infections: Lessons on willingness to participate and barriers to participation from ten German clinics serving behaviorally vulnerable men who have sex with men.

Future efficacy testing of interventions to prevent HIV or other infections will require engagement of vulnerable populations. We characterized willingness to participate in a future HIV vaccine trial and barriers to participation among men who have sex with men in a 12-month German cohort study. Among 1015 participants at enrollment, 604 (60%) reported willingness, 60 (6%) were unwilling, 351 (35%) were unsure or refused to answer. Among those unwilling, the primary reason was fear of getting HIV. Among those willing, reasons included protection against HIV and furthering scientific knowledge. In a multivariable logistic regression model, higher odds of willingness to participate were seen among participants at the 12-month visit (aOR: 1.09, 95% CI: 1.04-1.15) and with prior knowledge of HIV vaccine research (aOR: 1.14, 95% CI: 1.06-1.23). Educating potential participants about vaccine research may facilitate recruitment and participation in future trials of HIV vaccine candidates and other prevention interventions.

Achieving the third 95 in sub-Saharan Africa: application of machine learning approaches to predict viral failure.

OBJECTIVE: Viral failure in people with HIV (PWH) may be influenced by multiple sociobehavioral, clinical, and context-specific factors, and supervised learning approaches may identify novel predictors. We compared the performance of two supervised learning algorithms to predict viral failure in four African countries. DESIGN: Cohort study. METHODS: The African Cohort Study is an ongoing, longitudinal cohort enrolling PWH at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. Participants underwent physical examination, medical history-taking, medical record extraction, sociobehavioral interviews, and laboratory testing. In cross-sectional analyses of enrollment data, viral failure was defined as a viral load at least 1000 copies/ml among participants on antiretroviral therapy (ART) for at least 6 months. We compared the performance of lasso-type regularized regression and random forests by calculating area under the curve (AUC) and used each to identify factors associated with viral failure; 94 explanatory variables were considered. RESULTS: Between January 2013 and December 2020, 2941 PWH were enrolled, 1602 had been on antiretroviral therapy (ART) for at least 6 months, and 1571 participants with complete case data were included. At enrollment, 190 (12.0%) had viral failure. The lasso regression model was slightly superior to the random forest in its ability to identify PWH with viral failure (AUC: 0.82 vs. 0.75). Both models identified CD4 + count, ART regimen, age, self-reported ART adherence and duration on ART as important factors associated with viral failure. CONCLUSION: These findings corroborate existing literature primarily based on hypothesis-testing statistical approaches and help to generate questions for future investigations that may impact viral failure.

Epidemiology of Tuberculosis Among People Living With HIV in the African Cohort Study From 2013 to 2021.

BACKGROUND: The prevalence and incidence of tuberculosis (TB) is high among people living with HIV (PLWH) but is often underdiagnosed in HIV programmatic settings. SETTING: President's Emergency Plan for AIDS Relief (PEPFAR)-supported research sites in Uganda, Kenya, Tanzania, and Nigeria. METHODS: All patients underwent molecular testing at entry into a longitudinal cohort of PLWH and annually thereafter. We assessed the prevalence and incidence of TB and identified clinical and demographic factors associated with prevalent and incident TB using logistic regression and Cox proportional hazard models. RESULTS: From 21 January, 2013, to 1 December 2021, 3171 PLWH were enrolled with a TB prevalence of 3% (n = 93). Of the cases with prevalent TB, 66% (n = 61) were bacteriologically confirmed. The adjusted odds of prevalent TB were significantly higher among those with higher educational attainment, PLWH for 1-5 years since their HIV diagnosis, those who were underweight, and those with CD4 counts <200 cells/mm 3 . The overall TB incidence rate was 600 per 100,000 person-years (95% CI: 481-748). We found that shorter time since HIV diagnosis, being underweight, taking antiretroviral therapy <6 months, and having a CD4 count <200 cells/mm 3 were significantly associated with incident TB. PLWH on dolutegravir/lamivudine/tenofovir had a 78% lower risk of incident TB compared with those on tenofovir/lamivudine/efavirenz (hazard ratio: 0.22; 95% CI: 0.08-0.63). CONCLUSION: The prevalence and incidence of TB was notably high in this cohort sourced from PEPFAR clinics. Aggressive efforts to enhance HIV diagnosis and optimize treatment in programmatic settings are warranted to reduce the risk of HIV-TB co-occurrence in this cohort.

Weight gain during the dolutegravir transition in the African Cohort Study.

INTRODUCTION: Dolutegravir (DTG) has become a preferred component of first-line antiretroviral therapy (ART) in many settings but may be associated with excess weight gain. We evaluated changes in weight and body mass index (BMI) after switch to single-tablet tenofovir/lamivudine/dolutegravir (TLD) by people living with HIV (PLWH) in four African countries. METHODS: The African Cohort Study (AFRICOS) prospectively follows adults with and without HIV in Kenya, Uganda, Tanzania and Nigeria. Demographics, ART regimen, weight, BMI and waist-to-hip ratio were collected every 6 months. Multivariable Cox proportional hazards modelling was used to estimate hazard ratios and 95% confidence intervals (CIs) for factors associated with developing a BMI ≥25 kg/m2 . Linear mixed effects models with random effects were used to examine the average change in BMI, weight and waist-to-hip ratio. RESULTS: From 23 January 2013 to 1 December 2020, 2950 PLWH were enrolled in AFRICOS and 1474 transitioned to TLD. In adjusted models, PLWH on TLD had 1.77 times the hazard of developing a high BMI (95% CI: 1.22-2.55) compared to PLWH on non-TLD ART. Examining change in weight among all PLWH on ART, participants on TLD gained an average of 0.68 kg (95% CI: 0.32-1.04) more than PLWH on other regimens after adjusting for duration on ART, sex, age, study site and CD4 nadir. Among participants who switched to TLD, the average change in weight prior to TLD switch was 0.35 kg/year (95% CI: 0.25-0.46) and average change in weight was 1.46 kg/year (95% CI: 1.18-1.75) in the year following transition to TLD after adjustment for confounders. CONCLUSIONS: Elevated BMI and weight gain among PLWH on TLD are concerning safety signals. Implications for the development of metabolic comorbidities should be monitored, particularly if annual weight gain persists during continued follow-up after transitioning to TLD.

Non-communicable diseases by age strata in people living with and without HIV in four African countries.

INTRODUCTION: Non-communicable diseases (NCDs) are an important driver of morbidity among ageing people living with HIV (PLWH). We examined the composite role of age and HIV status on NCDs in people living with and without HIV. METHODS: The African Cohort Study (AFRICOS) prospectively enrols participants aged ≥15 years with and without HIV at 12 sites in Kenya, Tanzania, Uganda and Nigeria. From 21 January 2013 to 1 September 2021, we assessed participants for renal insufficiency (estimated glomerular filtration rate <60 ml/minute/1.73 m2 ), elevated blood pressure (BP) (any systolic BP >139 mmHg or diastolic BP >89 mmHg), obesity (body mass index >30 kg/m2 ), diabetes mellitus (DM) (fasting glucose ≥126 mg/dl or antidiabetic medication) and dysglycemia (fasting glucose ≥99 mg/dl or non-fasting ≥199 mg/dl). Multivariable logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with each NCD. The main exposure of interest was a composite of HIV status and age dichotomized around 50 years. All models were adjusted for study site and sex. The renal insufficiency model was additionally adjusted for elevated BP and dysglycemia. RESULTS AND DISCUSSION: Of 3761 participants with age data, 557 (14.8%) were age ≥50, 2188 (58.2%) were females and 3099 (82.4%) were PLWH. At enrolment, the prevalence of elevated BP, dysglycemia, renal insufficiency and obesity were n = 128 (26.9%), n = 75 (15.8%), n = 8 (1.7%) and n = 40 (8.4%), respectively, for PLWH ≥50. Compared to people without HIV age <50, PLWH age ≥50 had increased adjusted odds of having DM (OR: 2.78, 95% CI: 1.49-5.16), dysglycemia (OR: 1.98, 95% CI: 1.51-2.61) and renal insufficiency (OR: 6.20, 95% CI: 2.31-16.66). There were significant differences by study site, specifically, participants from Nigeria had the highest odds of elevated BP, dysglycemia and renal insufficiency as compared to Uganda. CONCLUSIONS: There was a high burden of NCDs in this African cohort with differences by geographic region. In order to promote healthy ageing with HIV, screening and treatment for common NCDs should be incorporated into routine HIV care with attention paid to geographic heterogeneity to better allocate resources.

Clinical similarities and differences between two large HIV cohorts in the United States and Africa.

BACKGROUND: Washington, DC, and sub-Saharan Africa are both affected by generalized HIV epidemics. However, care for persons living with HIV (PLWH) and clinical outcomes may differ in these geographically and culturally diverse areas. We compared patient and clinical site characteristics among adult persons living with HIV (PLWH) enrolled in two longitudinal HIV cohort studies-the African Cohort Study (AFRICOS) and the DC Cohort. METHODS: The DC Cohort is a clinic-based city-wide longitudinal cohort comprised of PLWH attending 15 HIV clinics in Washington, DC. Patients' socio-demographic characteristics, clinical evaluations, and laboratory data are retrospectively collected from electronic medical records and limited manual chart abstraction. AFRICOS is a prospective observational cohort of PLWH and uninfected volunteers attending 12 select HIV care and treatment facilities in Nigeria, Kenya, Uganda and Tanzania. AFRICOS study participants are a subset of clinic patients who complete protocol-specific visits every 6 months with history and physical examination, questionnaire administration, and blood/sputum collection for ascertainment of HIV outcomes and comorbidities, and neurocognitive and functional assessments. Among participants aged ≥ 18 years, we generated descriptive statistics for demographic and clinical characteristics at enrollment and follow up and compared them using bivariable analyses. RESULTS: The study sample included 2,774 AFRICOS and 8,420 DC Cohort participants who enrolled from January 2013 (AFRICOS)/January 2011 (DC Cohort) through March 2018. AFRICOS participants were significantly more likely to be women (58.8% vs 27.1%) and younger (83.3% vs 61.1% aged < 50 years old) and significantly less likely to be MSM (only 0.1% of AFRICOS population reported MSM risk factor) than DC Cohort. Similar rates of current viral suppression (about 75% of both samples), hypertension, hepatitis B coinfection and alcohol use were observed. However, AFRICOS participants had significantly higher rates of CD4<200 and tuberculosis and significantly lower rates of obesity, DM, hepatitis C coinfection and syphilis. CONCLUSIONS: With similar viral suppression outcomes, but many differences between our cohorts noted, the combined sample provides unique opportunities to assess and compare HIV care and treatment outcomes in the U.S. and sub-Saharan Africa. Comparing these two cohorts may inform care and treatment practices and may pave the way for future pathophysiologic analyses.

Dissecting drivers of immune activation in chronic HIV-1 infection.

BACKGROUND: Immune activation is a significant contributor to HIV pathogenesis and disease progression. In virally-suppressed individuals on ART, low-level immune activation has been linked to several non-infectious comorbid diseases. However, studies have not been systematically performed in sub-Saharan Africa and thus the impact of demographics, ART and regional endemic co-infections on immune activation is not known. We therefore comprehensively evaluated in a large multinational African cohort markers for immune activation and its distribution in various settings. METHODS: 2747 specimens from 2240 people living with HIV (PLWH) and 477 without HIV from the observational African Cohort Study (AFRICOS) were analyzed for 13 immune parameters. Samples were collected along with medical history, sociodemographic and comorbidity data at 12 HIV clinics across 5 programs in Uganda, Kenya, Tanzania and Nigeria. Data were analyzed with univariate and multivariate methods such as random forests and principal component analysis. FINDINGS: Immune activation was markedly different between PLWH with detectable viral loads, and individuals without HIV across sites. Among viremic PLWH, we found that all immune parameters were significantly correlated with viral load except for IFN-α. The overall inflammatory profile was distinct between men and women living with HIV, in individuals off ART and with HIV viremia. We observed stronger differences in the immune activation profile with increasing viremia. Using machine learning methods, we found that geographic differences contributed to unique inflammatory profiles. We also found that among PLWH, age and the presence of infectious and/or noninfectious comorbidities showed distinct inflammatory patterns, and biomarkers may be used to predict the presence of some comorbidities. INTERPRETATION: Our findings show that chronic immune activation in HIV-1 infection is influenced by HIV viral load, sex, age, region and ART use. These predictors, as well as associations among some biomarkers and coinfections, influence biomarkers associated with noncommunicable diseases. FUNDING: This work was supported by the President's Emergency Plan for AIDS Relief via a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11-2-0174, W81XWH-18-2-0040]. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70-25. This article was prepared while Michael A. Eller was employed at Henry M. Jackson Foundation for the Advancement of Military Medicine for the U.S. Military HIV Research Program. The views expressed are those of the authors and should not be construed to represent the positions of the US Army or the Department of Defense. The opinions expressed in this article are the author's own, and do not reflect the view of the National Institutes of Health, the U.S. Department of Health and Human Services, or the U.S. government.

Decreasing time to antiretroviral therapy initiation after HIV diagnosis in a clinic-based observational cohort study in four African countries.

INTRODUCTION: World Health Organization (WHO) guidelines have shifted over time to recommend earlier initiation of antiretroviral therapy (ART) and now encourage ART initiation on the day of HIV diagnosis, if possible. However, barriers to ART access may delay initiation in resource-limited settings. We characterized temporal trends and other factors influencing the interval between HIV diagnosis and ART initiation among participants enrolled in a clinic-based cohort across four African countries. METHODS: The African Cohort Study enrols adults engaged in care at 12 sites in Uganda, Kenya, Tanzania and Nigeria. Participants provide a medical history, complete a physical examination and undergo laboratory assessments every six months. Participants with recorded dates of HIV diagnosis were categorized by WHO guideline era (<2006, 2006 to 2009, 2010 to 2012, 2013 to 2015, ≥2016) at the time of diagnosis. Cox proportional hazard modelling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for time to ART initiation. RESULTS AND DISCUSSION: From January 2013 to September 2019, a total of 2888 adults living with HIV enrolled with known diagnosis dates. Median time to ART initiation decreased from 22.0 months (interquartile range (IQR) 4.0 to 77.3) among participants diagnosed prior to 2006 to 0.5 months (IQR 0.2 to 1.8) among those diagnosed in 2016 and later. Comparing those same periods, CD4 nadir increased from a median of 166 cells/mm3 (IQR: 81 to 286) to 298 cells/mm3 (IQR: 151 to 501). In the final adjusted model, participants diagnosed in each subsequent WHO guideline era had increased rates of ART initiation compared to those diagnosed before 2006. CD4 nadir ≥500 cells/mm3 was independently associated with a lower rate of ART initiation as compared to CD4 nadir <200 cells/mm3 (HR: 0.32; 95% CI: 0.28 to 0.37). Age >50 years at diagnosis was independently associated with shorter time to ART initiation as compared to 18 to 29 years (HR: 1.38; 95% CI: 1.19 to 1.61). CONCLUSIONS: Consistent with changing guidelines, the interval between diagnosis and ART initiation has decreased over time. Still, many adults living with HIV initiated treatment with low CD4, highlighting the need to diagnose HIV earlier while improving access to immediate ART after diagnosis.