Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis.

BACKGROUND: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. METHODS: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs). RESULTS: Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. CONCLUSIONS: While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.

HIV infection among children and adolescents in Burundi, Cameroon, and the Democratic Republic of Congo.

Evidence demonstrates a substantial HIV epidemic among children and adolescents in countries with long-standing generalized HIV epidemics, where availability of prevention of mother-to-child transmission services has historically been limited. The objective of this research was to explore factors associated with antiretroviral therapy (ART) initiation and morbidity among HIV-infected surviving children 2-17 years of age attending HIV programs in Central Africa. Programmatic data from 404 children attending HIV programs in Burundi, Cameroon, and the Democratic Republic of Congo (DRC) were included in our evaluation. Children were followed prospectively from 2008 to 2011 according to each clinic's standard of care. Diagnosis at a reference hospital was significantly associated with not having initiated ART (adjusted odds ratio, AOR = 0.40; 95% confidence interval, CI, 0.24-0.67). Being seen at a clinic in Cameroon (AOR = 0.45; 95%CI = 0.24-0.85) and being in school were associated with decreased risk (AOR = 0.55; 95%CI = 0.31-0.96). Being ART-naïve (AOR = 1.88; 95%CI = 1.20-2.94) and being diagnosed at a reference hospital (AOR = 2.39; 95%CI = 1.29-4.41) or other testing facility (AOR = 2.86; 95%CI = 1.32-6.18) were associated with increased risk of having a morbid event at the initial visit. In longitudinal analysis of incident morbidity, we found a decreased risk associated with attending clinics in Cameroon (adjusted hazard ratio, AHR = 0.23; 95%CI = 0.11-0.46) and the DRC (AHR = 0.46; 95%CI = 0.29-0.74), and an increased risk associated with being ART-naïve (AHR = 1.83; 95%CI = 1.12-2.97). We found a high burden of HIV-related health problems among children receiving care in this setting. Children face significant barriers to accessing HIV services, and the HIV epidemic among surviving children in the Central African region has not been adequately evaluated nor addressed.

Characteristics of antiretroviral therapy-naïve patients lost-to-care in HIV clinics in Democratic Republic of Congo, Cameroon, and Burundi.

Antiretroviral therapy (ART)-naïve patients are vulnerable to becoming lost-to-care (LTC) because they are not monitored as often as patients on treatment. We examined data from 19,461 HIV positive adults at 10 HIV clinics in Democratic Republic of Congo (DRC), Cameroon, and Burundi participating in the Phase 1 International epidemiologic Databases to Evaluate AIDS Central Africa (IeDEA-CA) study. Patients were LTC if they were ART-naïve and did not return within 7 months of the end of data collection. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with LTC. Of 5353 ART-naïve patients, 4420 (83%) were LTC and 933 (17%) were in-care. The odds of being LTC were greatest among patients from DRC (OR = 2.16, CI: 1.64-2.84, p < .0001), males (OR = 1.39, CI: 1.15-1.69, p = .0009), and ages 18-49 (OR = 1.45, CI: 1.16-1.82, p = .001). The odds of being LTC were least among patients with a WHO Clinical Stage of 1 or 2 (OR = 0.65, CI: 0.55-0.77, p < .0001) and in a perceived concordant relationship (OR = 0.61, CI: 0.43-0.87, p < .0001). LTC patients were more likely to have characteristics associated with higher risk for HIV transmission and progression. Many entered care at advanced stages and were less likely to know their partner's serostatus. Greater efforts to retain ART-naïve patients may increase earlier initiation of ART.

Spatial analysis of HIV infection and associated individual characteristics in Burundi: indications for effective prevention.

BACKGROUND: Adequate resource allocation is critical in the battle against HIV/AIDS, especially in Africa. The determination of the location and nature of HIV services to implement must comply with the geographic, social and behavioral characteristics of patients. We therefore investigated the spatial heterogeneity of HIV prevalence in Burundi and then assessed the association of social and behavioral characteristics with HIV infection accounting for the spatial heterogeneity. METHODS: We used data from the 2010 Demographic and Health Survey. We analyzed these data with a geostatistical approach (which takes into account spatial autocorrelation) by i) interpolating HIV data using the kernel density estimation, ii) identifying the spatial clusters with high and low HIV prevalence using the Kulldorff spatial scan statistics, and then iii) performing a multivariate spatial logistic regression. RESULTS: Overall HIV prevalence was 1.4 %. The interpolated data showed the great spatial heterogeneity of HIV prevalence (from 0 to 10 %), independently of administrative boundaries. A cluster with high HIV prevalence was found in the capital city and adjacent areas (3.9 %; relative risk 3.7, p < 0.001) whereas a cluster with low prevalence straddled two southern provinces (0 %; p = 0.02). By multivariate spatial analysis, HIV infection was significantly associated with the female sex (posterior odds ratio [POR] 1.36, 95 % credible interval [CrI] 1.13-1.64), an older age (POR 1.97, 95 % CrI 1.26-3.08), the level of education (POR 1.50, 95 % CrI 1.22-1.84), the marital status (POR 1.86, 95 % CrI 1.23-2.80), a higher wealth index (POR 2.11, 95 % CrI 1.77-2.51), the sexual activity (POR 1.76, 95 % CrI 1.04-2.96), and a history of sexually transmitted infection (POR 2.03, 95 % CrI 1.56-2.64). CONCLUSIONS: Our study, which shows where and towards which populations HIV resources should be allocated, could help national health policy makers develop an effective HIV intervention in Burundi. Our findings support the strategy of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for country-specific, in-depth analyses of HIV epidemics to tailor national prevention responses.

Hypertension and associated factors in HIV-infected patients receiving antiretroviral treatment in Burundi: a cross-sectional study.

Currently, the life expectancy of people living with the human immunodeficiency virus (HIV) and the general population are similar. Hypertension is a major public health issue in Africa and is largely underdiagnosed. Most HIV-infected individuals, especially those on Anti-Retroviral Therapy (ART) have hypertension. Our project aims to determine the prevalence of hypertension and associated factors amongst HIV-infected adults treated by ART in Burundi. A cross-sectional study was conducted among HIV-infected subjects over the age of 20, managed in five healthcare centers for people living with HIV (PLWH). The World Health Organization STEPWISE survey and anthropometric measurements were employed. Blood pressure was measured according to the ESC 2018 recommendations. 1 250 HIV-infected patients aged between 35.4 and 50.2 years were included (18.4% men). The prevalence of hypertension was 17.4% (95% CI 13.2-22.1). Approximately 47.25% of HIV patients with hypertension were previously undiagnosed. Other factors were associated with HTN, such as being overweight (OR 2.88; 95% CI 1.46-5.62), obesity (OR 2.65; 95% CI 1.27-5.55), longer duration of HIV infection: ≥ 10 years (OR 1.04; 95% CI 1.14-3.20), diabetes (OR 2.1; 95% CI 1.37-3.32) and age (OR 1.13; 95% CI 1.09-1.14). Despite their young age, almost 20% of HIV-ART treated patients had hypertension, 50% of these were undiagnosed. Blood pressure monitoring is crucial in these patients, especially those identified as high-risk, with prompt life and disability-saving interventions.

COVID-19 associated changes in HIV service delivery over time in Central Africa: Results from facility surveys during the first and second waves of the pandemic.

INTRODUCTION: The COVID-19 pandemic has impacted population health around the globe, directly and indirectly. The objective of this study was to document changes in HIV care associated with the COVID-19 pandemic at selected clinics in Central Africa, along with clinic-level strategies for minimizing disruptions in HIV care and treatment for people with HIV (PWH). METHODS: A 51-item questionnaire on COVID-19 pandemic-associated changes in HIV service delivery was completed by clinicians involved in HIV care at 21 clinics in five countries participating in Central Africa International epidemiology Databases to Evaluate AIDS (CA-IeDEA). The survey was completed at two timepoints: June-July 2020 and October 2020 to February 2021. Descriptive statistics were used to characterize changes in HIV care and related services. RESULTS: While 81% of sites reported at least one negative consequence of COVID-19 for clinic operations during the first survey, none reported suspending antiretroviral therapy (ART) initiation services for new patients, and 24% reported adopting telemedicine. In the follow-up survey, fewer sites (48%) reported at least one disruption to clinic operations, and more sites reported mitigation strategies, including expanding rapid ART initiation services and providing extra supplies of ART medications to reduce visit frequency. In the follow-up survey, more sites, especially in Rwanda, reported stockouts of commodities, including HIV and viral load testing and HIV pre-exposure prophylaxis. More than one-fifth of sites reported stockouts of second- or third-line ART at each survey timepoint. CONCLUSIONS: While the initial wave of the COVID-19 pandemic resulted in concerning disruptions to HIV service delivery at CA-IeDEA sites, most of these disruptions attenuated over time, and many sites introduced measures to help PWH avoid frequent visits to the clinic for care and medications. The impact of HIV commodity stockouts and clinic mitigation strategies on treatment outcomes needs to be assessed.

Prevalence of chronic kidney disease among people living with HIV/AIDS in Burundi: a cross-sectional study.

BACKGROUND: Since little is known about chronic kidney disease (CKD) among people living with HIV/AIDS (PLWHA) in Sub-Saharan Africa, the prevalence and nature of CKD were assessed in Burundi through a multicenter cross-sectional study. METHODS: Patients underwent assessments at baseline and 3 months later. Glomerular Filtration Rate (GFR) was estimated using abbreviated 4-variable Modification of Diet in Renal Diseases (MDRD) and Cockroft-Gault estimation methods. Patients were classified at month 3 into various CKD stages using the National Kidney Foundation (NKF) definition, which combines GFR and urinary abnormalities. Risk factors for presence of proteinuria (PRO) and aseptic leukocyturia (LEU) were further analyzed using multiple logistic regression. RESULTS: Median age of the patients in the study (N = 300) was 40 years, 70.3% were female and 71.7% were on highly active antiretroviral therapy. Using the MDRD method, CKD prevalence in patients was 45.7%, 30.2% of whom being classified as stage 1 according to the NKF classification, 13.5% as stage 2 and 2% as stage 3. No patient was classified as stage 4 or 5. Among CKD patients with urinary abnormality, PRO accounted for 6.1% and LEU for 18.4%. Significant associations were found between LEU and non-steroidal anti-inflammatory drug (NSAID) use, previous history of tuberculosis, low body mass index and female gender and between PRO and high viral load. CONCLUSION: Our study, using a very sensitive definition for CKD evaluation, suggests a potentially high prevalence of CKD among PLWHA in Burundi. Patients should be regularly monitored and preventative measures implemented, such as monitoring NSAID use and adjustment of drug dosages according to body weight. Urine dipsticks could be used as a screening tool to detect patients at risk of renal impairment.

HIV clinical stages and lower extremity arterial disease among HIV infected outpatients in Burundi.

Chronic disease of people living with human immunodeficiency virus (HIV) infection are now approaching those of the general population. Previous, in vitro studies shown that HIV causes arterial injuries resulting in inflammation and atherosclerosis but direct relationship between HIV infection clinical stages and lower extremity arterial disease (LEAD) remain controversial. No study assessed, with an accurate method, both the prevalence of LEAD and the influence of HIV severity on LEAD in HIV outpatients in Central Africa. A cross-sectional study was conducted among 300 HIV-infected outpatients, aged ≥ 40 years in Bujumbura, Burundi. All patients underwent ankle-brachial index (ABI) measurement and LEAD was diagnosed by ABI ≤ 0.9. The prevalence of LEAD was 17.3% (CI 95% 13.2-22.1). The mean age was 49.6 ± 7.1 years. On multivariable analysis, factors associated with LEAD were hypertension (OR = 2.42; 95% CI 1.10-5.80), and stage IV HIV clinical infection (OR = 4.92, 95% CI 1.19-20.36). This is the first study performed on a large HIV population in Central Africa, reporting high LEAD prevalence. It underlines the influence of HIV infection on peripheral atherosclerosis at latest clinical stages and the need for LEAD screening in HIV-infected patients.

Comparison of cohort characteristics in Central Africa International Epidemiology Databases to Evaluate AIDS and Demographic Health Surveys: Rwanda and Burundi.

Clinical health record data are used for HIV surveillance, but the extent to which these data are population representative is not clear. We compared age, marital status, body mass index, and pregnancy distributions in the Central Africa International Databases to Evaluate AIDS (CA-IeDEA) cohorts in Burundi and Rwanda to all people living with HIV and the subpopulation reporting receiving a previous HIV test result in the Demographic and Health Survey (DHS) data, restricted to urban areas, where CA-IeDEA sites are located. DHS uses a probabilistic sample for population-level HIV prevalence estimates. In Rwanda, the CA-IeDEA cohort and DHS populations were similar with respect to age and marital status for men and women, which was also true in Burundi among women. In Burundi, the CA-IeDEA cohort had a greater proportion of younger and single men than the DHS data, which may be a result of outreach to sexual minority populations at CA-IeDEA sites and economic migration patterns. In both countries, the CA-IeDEA cohorts had a higher proportion of underweight individuals, suggesting that symptomatic individuals are more likely to access care in these settings. Multiple sources of data are needed for HIV surveillance to interpret potential biases in epidemiological data.

Retention and mortality on antiretroviral therapy in sub-Saharan Africa: collaborative analyses of HIV treatment programmes.

INTRODUCTION: By 2020, 90% of all people diagnosed with HIV should receive long-term combination antiretroviral therapy (ART). In sub-Saharan Africa, this target is threatened by loss to follow-up in ART programmes. The proportion of people retained on ART long-term cannot be easily determined, because individuals classified as lost to follow-up, may have self-transferred to another HIV treatment programme, or may have died. We describe retention on ART in sub-Saharan Africa, first based on observed data as recorded in the clinic databases, and second adjusted for undocumented deaths and self-transfers. METHODS: We analysed data from HIV-infected adults and children initiating ART between 2009 and 2014 at a sub-Saharan African HIV treatment programme participating in the International epidemiology Databases to Evaluate AIDS (IeDEA). We used the Kaplan-Meier method to calculate the cumulative incidence of retention on ART and the Aalen-Johansen method to calculate the cumulative incidences of death, loss to follow-up, and stopping ART. We used inverse probability weighting to adjust clinic data for undocumented mortality and self-transfer, based on estimates from a recent systematic review and meta-analysis. RESULTS: We included 505,634 patients: 12,848 (2.5%) from Central Africa, 109,233 (21.6%) from East Africa, 347,343 (68.7%) from Southern Africa and 36,210 (7.2%) from West Africa. In crude analyses of observed clinic data, 52.1% of patients were retained on ART, 41.8% were lost to follow-up and 6.0% had died 5 years after ART initiation. After accounting for undocumented deaths and self-transfers, we estimated that 66.6% of patients were retained on ART, 18.8% had stopped ART and 14.7% had died at 5 years. CONCLUSIONS: Improving long-term retention on ART will be crucial to attaining the 90% on ART target. Naïve analyses of HIV cohort studies, which do not account for undocumented mortality and self-transfer of patients, may severely underestimate both mortality and retention on ART.

HIV type 1 diversity and antiretroviral drug resistance mutations in Burundi.

In 2002, an HIV surveillance study was performed among more than 5500 individuals representing the general population of urban and rural districts in Burundi. In this report, we genetically characterized a subset of the HIV-1-positive samples identified during this survey, including all the HIV-positive samples from Bujumbura, the capital city, and samples from one semiurban and one rural district. One hundred and nineteen samples were genetically characterized in the V3-V5 region of the env gene and/or in the protease and reverse transcriptase region of the pol gene. Phylogenetic analysis of 101 env/pol sequences revealed that the HIV-1 epidemic in Burundi was driven by subtype C (81.2%), followed by subtype A (7.9 %) and polC/envA recombinants (5.9%). One major mutation associated with resistance to antiretroviral drugs (ARVs) in the pol gene, as defined by the International AIDS Society Resistance Testing-USA panel, was observed in one individual, but many minor resistance-associated mutations were also present in the majority of the samples.

Older Adults Accessing HIV Care and Treatment and Adherence in the IeDEA Central Africa Cohort.

Background. Very little is known about older adults accessing HIV care in sub-Saharan Africa. Materials and Methods. Data were obtained from 18,839 HIV-positive adults at 10 treatment programs in Burundi, Cameroon, and the Democratic Republic of Congo. We compared characteristics of those aged 50+ with those aged 18-49 using chi-square tests. Logistic regression was used to determine if age was associated with medication adherence. Results. 15% of adults were 50+ years. Those aged 50+ were more evenly distributed between women and men (56% versus 44%) as compared to those aged 18-49 (71% versus 29%) and were more likely to be hypertensive (8% versus 3%) (P < 0.05). Those aged 50+ were more likely to be adherent to their medications than those aged 18-49 (P < 0.001). Adults who were not heavy drinkers reported better adherence as compared to those who reported drinking three or more alcoholic beverages per day (P < 0.001). Conclusions. Older adults differed from their younger counterparts in terms of medication adherence, sociodemographic, behavioral, and clinical characteristics.

Adult HIV care resources, management practices and patient characteristics in the Phase 1 IeDEA Central Africa cohort.

INTRODUCTION: Despite recent advances in the management of HIV infection and increased access to treatment, prevention, care and support, the HIV/AIDS epidemic continues to be a major global health problem, with sub-Saharan Africa suffering by far the greatest humanitarian, demographic and socio-economic burden of the epidemic. Information on HIV/AIDS clinical care and established cohorts' characteristics in the Central Africa region are sparse. METHODS: A survey of clinical care resources, management practices and patient characteristics was undertaken among 12 adult HIV care sites in four countries of the International Epidemiologic Databases to Evaluate AIDS Central Africa (IeDEA-CA) Phase 1 regional network in October 2009. These facilities served predominantly urban populations and offered primary care in the Democratic Republic of Congo (DRC; six sites), secondary care in Rwanda (two sites) and tertiary care in Cameroon (three sites) and Burundi (one site). RESULTS: Despite some variation in facility characteristics, sites reported high levels of monitoring resources, including electronic databases, as well as linkages to prevention of mother-to-child HIV transmission programs. At the time of the survey, there were 21,599 HIV-positive adults (median age=37 years) enrolled in the clinical cohort. Though two-thirds were women, few adults (6.5%) entered HIV care through prevention of mother-to-child transmission services, whereas 55% of the cohort entered care through voluntary counselling and testing. Two-thirds of patients at sites in Cameroon and DRC were in WHO Stage III and IV at baseline, whereas nearly all patients in the Rwanda facilities with clinical stage information available were in Stage I and II. WHO criteria were used for antiretroviral therapy initiation. The most common treatment regimen was stavudine/lamivudine/nevirapine (64%), followed by zidovudine/lamivudine/nevirapine (19%). CONCLUSIONS: Our findings demonstrate the feasibility of establishing large clinical cohorts of HIV-positive individuals in a relatively short amount of time in spite of challenges experienced by clinics in resource-limited settings such as those in this region. Country differences in the cohort's site and patient characteristics were noted. This information sets the stage for the development of research initiatives and additional programs to enhance adult HIV care and treatment in Central Africa.