WHO HIV Research Articles

Antiretroviral therapy initiation and outcomes of hospitalized HIV-infected patients in Uganda-An evaluation of the HIV test and treat strategy.

Uganda adopted the HIV Test and Treat in 2016. There is paucity of data about its implementation among hospitalized patients. We aimed to determine the proportion of patients initiating anti-retroviral therapy (ART) during hospitalization, barriers and mortality outcome. In this mixed methods cohort study, we enrolled hospitalized patients with a recent HIV diagnosis from three public hospitals in Uganda. We collected data on clinical characteristics, ART initiation and reasons for failure to initiate ART, as well as 30 day outcomes. Healthcare workers in-depth interviews were also conducted and data analyzed by sub-themes. We enrolled 234 patients; females 140/234 (59.8%), median age 34.5 years (IQR 29-42), 195/234 (83.7%) had WHO HIV stage 3 or 4, and 74/116 (63.8%) had CD4 ≤ 200 cell/μL. The proportion who initiated ART during hospitalization was 123/234 (52.6%) (95% CI 46.0-59.1), of these 35/123 (28.5%) initiated ART on the same day of hospitalization, while 99/123 (80.5%) within a week of hospitalization. By 30 days 34/234 (14.5%) (95% CI 10.3-19.7) died. Patients residing ≥ 35 kilometers from the hospital were more likely not to initiate ART during hospitalization, [aRR = 1.39, (95% CI 1.22-1.59). Inadequate patient preparation for ART initiation and advanced HIV disease were highlighted as barriers of ART initiation during hospitalization. In this high HIV prevalence setting, only half of newly diagnosed HIV patients are initiated on ART during hospitalization. Inadequate pre-ART patient preparation and advanced HIV are barriers to rapid ART initiation among hospitalized patients in public hospitals.

U.S. Women Need the Dapivirine Ring, Too: FDA as Structural Barrier to HIV Prevention for Women.

The dapivirine monthly vaginal ring-a discreet, anti-HIV microbicide created specifically for women-has received a positive scientific opinion by the European Medicines Agency and is included in the WHO HIV prevention guidelines. It has received regulatory approvals in several countries in southern and eastern Africa. During the review of the New Drug Application that was submitted in December 2020, FDA advised the developer, International Partnership for Microbicides, that it was unlikely to be approved in the United States; the application has since been withdrawn. This commentary will present the case for FDA approval for the dapivirine ring. Advocacy is urgently needed to protect U.S. women's access to user-controlled HIV prevention technologies, consistent with both global regulatory decisions to date and with a reproductive justice framework. Women continue to need the fullest range of HIV prevention methods to integrate into their lives in the most practical and effective way possible.

Dolutegravir for children with HIV-associated tuberculosis

In The Lancet HIV, Anna Turkova and colleagues1 report the findings of a pharmacokinetic and safety substudy nested within the ODYSSEY trial, which provides evidence that twice-daily dolutegravir dosing is safe and effective when used with rifampicin-containing tuberculosis (TB) treatment in children with HIV-associated TB. Their findings support the 2021 WHO HIV recommendations for once-daily dolutegravir as a component of first-line and second-line HIV treatment from age 4 weeks or older, and twice-daily dosing during treatment with rifampicin-based therapy for TB coinfection.

Incidence, risk factors, and outcomes of acute kidney injury among hiv positive medical admissions at the Bamenda Regional Hospital

Background: There is a paucity of data on the burden of acute kidney injury (AKI) in hospitalized HIV-infected patients in Sub-Saharan Africa in the “test and treat” era. Objectives: To study the incidence, risk factors, and outcomes of AKI among HIV-positive medical admissions in a secondary hospital. Materials and methods: We prospectively screened adult HIV-positive patients who gave their informed consent and were admitted to the Bamenda Regional Hospital for AKI from February to June 2020. We excluded participants with Chronic Kidney Disease (CKD) Stage 5 and those with confounders of serum creatinine. On admission and after 2-7 days, we extracted a venous blood sample from each participant to evaluate serum creatinine and diagnose AKI. The participants were then followed up on until they were discharged or died. We measured the need for dialysis, access to dialysis, and renal recovery at three months for patients with AKI. The amended KDIGO 2012 criteria were used to define and classify AKI. The University of Bamenda’s institutional review board provided ethical approval. Results: A total of 206 participants (39.8% men) were enrolled, with a mean (SD) age of 45.71(13.13) years. On enrolment, 89.8% (n = 185) of the participants were on combination antiretroviral therapy (c-ART), with 81.6% (n = 151) on tenofovir-containing regimens. The WHO HIV clinical stages 3 and 4 were present in 81.5% (n = 168) of the individuals. The most common reason for hospitalization was opportunistic infections (69.8%; n = 142). AKI was found in 30.6% (n = 63) of the patients, with 58.7% (n = 37) of them being classified as KDIGO stage 3. A total of 12 (42.9%) participants out of the 28 in need, were dialyzed. AKI was independently associated with use of traditional medicines (aOR = 2.9; 95% CI 1.4-6.3; p = 0.006), WHO HIV stages 3 and 4 (aOR = 4.1; 95% CI 1.1-15.7; p = 0.038), hypotension (aOR = 3.3; 95% CI 1.4-7.8; p = 0.008) and low haemoglobin level ≤ 8.0 g/dl (aOR = 3.5; 95% CI 1.7-7.4; p = 0.001). The AKI group used to have a significantly higher mortality rate (42.9% vs. 16.1%; p < 0.001). Renal recovery was complete in 66.7% of the 30 survivors at three months, partial in 13.3%, and no recovery in 20% of the survivors. Conclusion: Despite the growing use of combination antiretroviral medication, significant immunosuppression is still common in hospitalized HIV-positive patients, increasing the risk of AKI and worsening prognosis. In this high-risk population, early detection of AKI with renal function monitoring may improve results.

Predictors of loss to follow-up from HIV antiretroviral therapy in Namibia.

Despite progress on population-level HIV viral suppression, unknown outcomes amongst people who have initiated antiretroviral therapy (ART) in low- and middle-income countries, commonly referred to as loss to follow-up (LTFU), remains a barrier. The mean global estimate of LTFU is 20%, exceeding the World Health Organization target of <15%. Pervasive predictors associated with LTFU include younger age, low body mass index, low CD4 count, advanced HIV clinical stage and certain ART regimens. In Namibia, ART use by eligible individuals exceeds 85%, surpassing the global average. Nonetheless, LTFU remains a barrier to achieving viral suppression and requires research to elucidate context-specific factors. An observational cohort study was conducted in Namibia in 2012 by administering surveys to individuals who presented for HIV care and initiated ART for the first time. Additional data were collected from routine medical data monitoring systems. Participants classified as LTFU at 12 months were traced to confirm their status. Predictors of LTFU were analyzed using multivariable logistic regression. Of those who presented consecutively to initiate ART, 524 were identified as eligible to enroll in the study, 497 enrolled, and 474 completed the baseline questionnaire. The cohort had mean age 36 years, 39% were male, mean CD4 cell count 222 cells/mm3, 17% were WHO HIV clinical stage III-IV, and 14% started efavirenz-based regimens. Tracing participants classified as LTFU yielded a re-categorization from 27.8% (n = 132) to 14.3% (n = 68) LTFU. In the final multivariable model, factors associated with confirmed LTFU status were: younger age (OR 0.97, 95% CI 1.00–1.06, p = 0.02); male sex (OR 2.34, CI 1.34–4.06, p = 0.003); difficulty leaving work or home to attend clinic (OR 2.55, CI 1.40–4.65, p = 0.002); and baseline efavirenz-based regimen (OR 2.35, CI 1.22–4.51, p = 0.01). Interventions to reduce LTFU should therefore target young men, particularly those who report difficulty leaving work or home to attend clinic and are on an efavirenz-based regimen.

Retention in care and predictors of attrition among HIV-infected patients who started antiretroviral therapy in Kinshasa, DRC, before and after the implementation of the 'treat-all' strategy.

The retention of patients in care is a key pillar of the continuum of HIV care. It has been suggested that the implementation of a "treat-all" strategy may favor attrition (death or lost to follow-up, as opposed to retention), specifically in the subgroup of asymptomatic people living with HIV (PLWH) with high CD4 counts. Attrition in HIV care could mitigate the success of universal antiretroviral therapy (ART) in resource-limited settings. We performed a retrospective study of PLWH at least 15 years old initiating ART in 85 HIV care centers in Kinshasa, Democratic Republic of Congo (DRC), between 2010 and 2019, with the objective of measuring attrition and to define factors associated with it. Sociodemographic and clinical characteristics recorded at ART initiation included sex, age, weight, height, WHO HIV stage, pregnancy, baseline CD4 cell count, start date of ART, and baseline and last ART regimen. Attrition was defined as death or loss to follow-up (LTFU). LTFU was defined as "not presenting to an HIV care center for at least 180 days after the date of a last missed visit, without a notification of death or transfer". Kaplan-Meier curves were used to present attrition data, and mixed effects Cox regression models determined factors associated with attrition. The results compared were before and after the implementation of the "treat-all" strategy. A total of 15,762 PLWH were included in the study. Overall, retention in HIV care was 83% at twelve months and 77% after two years of follow-up. The risk of attrition increased with advanced HIV disease and the size of the HIV care center. Time to ART initiation greater than seven days after diagnosis and Cotrimoxazole prophylaxis was associated with a reduced risk of attrition. The implementation of the "treat-all" strategy modified the clinical characteristics of PLWH toward higher CD4 cell counts and a greater proportion of patients at WHO stages I and II at treatment initiation. Initiation of ART after the implementation of the 'treat all" strategy was associated with higher attrition (p<0.0001) and higher LTFU (p<0.0001). Attrition has remained high in recent years. The implementation of the "treat-all" strategy was associated with higher attrition and LTFU in our study. Interventions to improve early and ongoing commitment to care are needed, with specific attention to high-risk groups to improve ART coverage and limit HIV transmission.

Effects of Undernutrition and Predictors on the Survival Status of HIV-Positive Children after Started Antiretroviral Therapy (ART) in Northwest Ethiopia.

Malnutrition and human immunodeficiency virus/acquired immunodeficiency syndrome have complex and multidirectional relationships. Ethiopia is one of the countries hardest hit by the HIV epidemic as well as malnutrition. This study was aimed at assessing the effects of undernutrition on the survival status of HIV-positive children who received HIV/AIDS care in Northwest Ethiopia. Materials and Methods. A facility-based retrospective follow-up was conducted from January 1, 2009, to December 31, 2020. The data was entered into EpiData version 4.2.0. Then, the entered data was exported to STATA 14 software for further analysis, and the Kaplan-Meier survival curve was used to estimate survival time after the initiation of ART. The Bivariable and multivariable Cox regression analyses were conducted to identify predictors of mortality associated with undernutrition. Results. The mean (±SD) age of participant children was found 118.4 (±38.24) months. The overall mortality rate in this study was determined as 5.4 per 100 child-years (95% CI: 3.6, 5.8). Children with CD4 cell counts below the threshold [AHR = 1.6; 95% CI (1.19, 7.85)], advanced WHO clinical stages (III and IV) HIV [AHR = 4.5; 95% CI (2.80, 8.40)], and being severe stunting at the beginning [AHR = 2.9; 95% CI (1.80, 6.40)] were significantly associated with mortality of HIV-positive children. Conclusion. The findings of the current study indicated that HIV-positive children on ART had a high rate of mortality. Baseline undernutrition has the mortality of children who had CD4 counts below a threshold, advanced WHO HIV clinical staging (III and IV), and being severe stunting (HAZ ≤ −3 Z score) which were found to be independent predictors for mortality of undernourished HIV.

Most Early-Treated Children With Perinatally Acquired HIV Have Preserved Lung Function at School Age.

Impaired lung function is common among older children with perinatally acquired HIV (PHIV) who initiated antiretroviral therapy (ART) late in childhood. We determined the prevalence of abnormal spirometry and cofactors for impaired lung function among school-age children with PHIV who initiated ART when aged 12 months or younger. Children who received early ART in the Optimizing Pediatric HIV-1 Therapy study in Kenya and underwent spirometry at school age. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured. Abnormal spirometry was defined as follows: obstructive (FEV1/FVC <1.64 z score [zFEV1/FVC]) and restricted (zFVC <1.64 with zFEV1/FVC ≥1.64). Characteristics, including anthropometric and HIV-related data, were ascertained in infancy and at school age. Caregiver carbon monoxide exposure served as a proxy for school-age child exposure. Linear regression determined associations of cofactors with lung function. Among 40 children, the median age was 5 months at ART initiation and 8.5 years at spirometry. The mean zFEV1, zFVC, and zFEV1/FVC (SD) were 0.21 (1.35), 0.31 (1.22), and -0.24 (0.82), respectively. Five (13%) children had abnormal spirometry. Spirometry z scores were significantly lower among children with pre-ART pneumonia, WHO HIV stage 3/4, higher HIV RNA at 6 months after ART initiation, low anthropometric z scores, and higher carbon monoxide exposure. Most of the children with PHIV who initiated ART at age 12 months or younger had normal spirometry, suggesting that ART in infancy preserved lung function. However, 13% had abnormal spirometry despite early ART. Modifiable factors were associated with impaired lung function, providing potential targets for interventions to prevent chronic lung disease.

727. Predictors of Depressive Symptoms in Pregnant Partners in Seroconcordant Couples Living with HIV in Zambézia Province, Mozambique

BackgroundDepression contributes to HIV treatment outcomes in sub-Saharan Africa, where approximately 15% of people living with HIV have comorbid depression. HoPS+, a cluster randomized trial among seroconcordant couples living with HIV, assesses male partner involvement during antenatal HIV care and HIV outcomes. We describe predictors of depressive symptoms among pregnant partners living with HIV in Zambézia Province, Mozambique.MethodsThis baseline cross-sectional analysis includes 1079 female HoPS+ participants. We show demographic (age, enrollment date, relationship status, education, and occupation) and clinical (WHO HIV stage, body mass index [BMI], and antiretroviral therapy [ART] use history) factors. We model females’ depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) using proportional odds models with continuous covariates as restricted cubic splines (enrollment date, age, BMI, partner’s PHQ-9 score), categorical covariates (district, relationship status, education, occupation, WHO stage), and ART use history. Missing covariates were imputed 20 times.ResultsParticipants’ median age was 23 (interquartile range [IQR] 20-28). Most women reported no or < 7 years of education (84.1%), were farmers (61.3%), and were WHO stage I (81.9%). They had a median PHQ-9 score of 3 (IQR 0-5) and 47 (43.6%) had moderately severe or severe depressive symptoms, with 19.6% missing PHQ-9 scores. Among 867 pregnant partners with PHQ-9s, demographic and clinical covariates were not meaningful predictors of PHQ-9 score. Male partner’s PHQ-9 score, however, was associated with (covariate-adjusted Spearman’s rho 0.58, 95% Confidence Interval [CI]: 0.51-0.65) and strongly predictive of a pregnant partner’s score (Figure). An increase in a male partner’s PHQ-9 score from 9 to 10 was associated with 1.47 times increased odds (95% CI: 1.37-1.58) of a ≥1-point increase in a woman’s PHQ-9 score Figure: Female Partner's Depressive Symptoms ConclusionDepressive symptoms are highly correlated among pregnant people and their partners, which may have implications for pregnancy care. Interventions aimed to reduce depressive symptoms and improve HIV-related outcomes during pregnancy may have greater success when focused on addressing both partners’ depressive symptoms. Disclosures All Authors: No reported disclosures

ENT manifestations in HIV infected patients in PIMS Islamabad.

INTRODUCTION&#x0D; HIV is a global pandemic with estimation of 38 million active cases around the world according to WHO HIV data and statistics 2019. Despite of advancement in medical field the disease has not been tamed uptil now. In this modern era HIV is still considered a taboo in Pakistan, people are reluctant about disclosure of disease, screening of their partners and its treatment which is due to lack of awareness and socio-economic constraints.&#x0D; OBJECTIVE&#x0D; The aim of this study is to see the incidence of Ear, Nose and Throat (ENT) manifestations in HIV infected people presented in tertiary care hospital of Islamabad.&#x0D; MATERIAL AND METHOD&#x0D; A one-year observational cross-sectional study conducted in Pakistan Institute of Medical Sciences (PIMS) Islamabad between January 2019 to December 2019. All the HIV infected patients who presented with ear, nose and throat manifestations were recruited in the study. Detailed history and examination were conducted after taking written consent. Analysis included calculations of mean values of quantitative association between ENT symptoms and demographic characteristics. Statistical analysis was estimated using either Chi-square test or t-test. &#x0D; RESULTS &#x0D; Majority of the patients presented with Otological manifestation of which the most common was chronic suppurative otitis media (14.28%). Most common Rhinological/Oropharyngeal manifestation included epistaxis (12.24%) and oral candidiasis (8.16%) respectively. Among neck manifestations cervical lymph adenopathy (18.16%) showed the highest percentage.&#x0D; CONCLUSION&#x0D; The study shows a local trend of ENT manifestation in which the patient presented in later stage (WHO III) which resembled to the studies carried out in other developing countries showing ineffectiveness of current national HIV/AIDS programme.

Implementation of Context Specific Diagnostics, Strategies and Resources for PMTCT Scale-up Programming in Conflict Affected Communities in Jos, Nigeria

The 2013 WHO HIV guidelines provided effective antiretroviral regimens to reduce perinatal transmission to below 2%. The option-B approach of providing antiretroviral drugs was adopted by Nigeria, which contributed 32% of global gaps in Preventing Mother to child transmission (PMTCT). In Plateau State, which had 7.7% HIV prevalence, incessant ethnoreligious conflict created challenges impacting on HIV service delivery and access to treatment centers. PMTCT diagnostics conducted by the lead HIV implementing Partner (IP), revealed that several communities in Jos, Plateau State, lacked HIV treatment centers, but were also unable to access existing centers because of conflict related partitioning of Jos, calling for specialized strategies and collaboration to scale-up to affected communities. To bridge existing challenges related to distrust amongst communities, the intervention strategy identified six community oriented resource persons (CORPs), of same ethnoreligious dispensation as people in affected communities, who also possessed HIV programing competencies, to lead the intervention. The project methodology included engagement of community gatekeepers and Plateau HIV stakeholders, who generated context specific strategies to enter these communities and scale-up HIV/PMTCT. The lead CORPs included a female public health/HIV physician, another clinician who owned a community hospital, a HIV laboratory personnel, a HIV trained Data officer, a religious cleric/youth leader and a female expert patient cum member of Federation of Muslim women association of Nigeria (FOMWAN). Collaborating with various stakeholders, they birthed a community faith based organization they called Muslim Health Initiative of Nigeria (MUHIN). This served as platform for community engagement to scale-up HIV/PMTCT services. The Lead HIV Partner supported, engaged and funded MUHIN to provide context specific scale-up to address existing gaps. MUHIN identified, assessed, upgraded and activated twenty-eight community clinics for HIV/PMTCT service deliver, building on existing Maternal, child and New-born health (MNCH) structures. They provided HIV trainings, MNCH materials, national data-capture tools and capacity building to the identified facilities, staff and CORPs. They stratified according to facility capacity, and linked them using the Hub-and-spoke model, to provide HIV testing, PMTCT and Antiretroviral therapy (ART) services. In order to bridge existing human resource for health gaps existing at the clinics, community health workers and HIV positive women who had successfully completed PMTCT programs were engaged and trained according to task shifting and task sharing (TSTS) guidelines, in preparation for HIV/PMTCT activation using HCT as entry. We conclude that detailed diagnostics, planning and utilization of context-specific strategies including TSTS are critical for successful project outcomes.

False reactive HIV rapid antibody test in pregnancy

Background: Universal screening of HIV infection in pregnant women is recommended by CDC as well as Indonesia Ministry of Health to prevent mother-to-child HIV transmission. Algorithm of HIV testing in pregnant women in Indonesia is similar to that in Integrated Counseling and Testing Centre (ICTC) which refes to WHO HIV Testing Strategy III. Pregnancy has been observed to be associated with false positive HIV testing that can cause serious emotional distress and unnecessary follow-up. Case Description: A 21 y old pregnant woman was referred to a tertiary hospital with premature rupture of the membranes. Before C-section, preoperative laboratory test panels were ordered, including for HIV to which she consented. A rapid HIV test (A1) was performed and tested reactive for antibodies against HIV. The second (A2) and third (A3) rapid tests were then performed and yielded non-reactive results, concluding the final result as negative. Reassessment of the patients showed no risk factors for HIV infection. This was the third case of reactive A1 with non-reactive A2 and A3 within the last year in the hospital. After confirmatory tests, which came back non-reactive and negative for fourth-generation HIV test and Western Blot, respectively, the A1 test was considered as false positive. Discussion: Based on several reports, there are alloantibodies in pregnancy, transfusions, transplantations, and autoimmune diseases that account for the increased false positive rate. Positive HIV antibody test results can occur in the absence of infection due to cross-reactivity between viral proteins and tested specimens, but such cross-reactivity is less common using current peptide-based EIAs which contain fewer antigens than previous viral lysate-based EIAs. However, clinicians should be aware that when HIV prevalence is low, as is often the case among pregnant women, a reactive EIA result is more likely to be false positive. Conclusion: Counselling and HIV test should be integrated in antenatal care. Diagnostic procedure of HIV test in pregnant women refers to WHO Testing Strategy III. Because the positive predictive value of HIV test in obstetric population is low, positive screening results should be handled carefully and appropriate confirmatory testing should always be pursued.

World Health Organization Human Immunodeficiency Oral Preexposure Prophylaxis Mobile App for Clinicians and Consumers

This department reviews the WHO HIV Oral PrEP mobile app for clinicians and consumers. Patricia Biller Krauskopf, PhD, FNP-BC, FAANP, is a professor and the Helen Zebarth chair in nursing at the Eleanor Wade Custer School of Nursing at Shenandoah University in Winchester, VA.

Effect of tuberculosis infection on mortality of HIV-infected patients in Northern Tanzania

BackgroundTB and HIV are public health problems, which have a synergistic effect to each other. Despite the decreasing burden of these two diseases they still make a significant contribution to mortality. Tanzania is among the 30 high TB and HIV burden countries.MethodsRoutine data over 6 years from people living with HIV (PLHIV) attending health facilities in three regions of Northern Tanzania were analyzed, showing mortality trends from 2012 to 2017 for HIV and HIV/TB subpopulations. Poisson regression with frailty model adjusting for clustering at health facility level was used to analyze the data to determine mortality rate ratios (RR) and 95% confidence intervals (95%CI).ResultsAmong all PLHIV the overall mortality rate was 28.4 (95% CI 27.6–29.2) deaths per 1000 person-years. For PLHIV with no evidence of TB the mortality rates was 26.2 (95% CI 25.4–27.0) per 1000 person-years, and for those with HIV/TB co-infection 57.8 (95% CI 55.6–62.3) per 1000 person-years. After adjusting for age, sex, residence, WHO stage, and bodyweight, PLHIV with TB co-infection had 40% higher mortality than those without TB (RR 1.4; 95% CI 1.24–1.67).ConclusionsOver the 6-year period mortality rates for HIV/TB patients were consistently higher than for PLHIV who have no TB. More efforts should be directed into improving nutritional status among HIV patients, as it has destructive interaction with TB for mortality. This will improve patients’ body weight and CD4 counts which are protective against mortality. Among PLHIV attention should be given to those who are in WHO HIV stage 3 or 4 and having TB co-infection.

Leaving no one behind: lessons from implementation of policies for universal HIV treatment to universal health coverage

BackgroundThe third Sustainable Development Goal (SDG − 3) aims to ensure healthy lives and promote well-being for all at all ages. SDG-3 has a specific target on universal health coverage (UHC), which emphasizes the importance of all people and communities having access to quality health services without risking financial hardship. The objective of this study is to review progress towards UHC using antiretroviral treatment (ART) as a case study.MethodsWe used a mixed-methods design including qualitative and quantitative approaches. We reviewed and synthesised the evidence on the evolution of the WHO HIV treatment guidelines between 2002 and 2019. We calculated ART coverage over time by gender, age group, and location. We also estimated ART coverage differences and ratios.FindingsART guidelines have evolved from “treating the sickest” to “treating all”. ART coverage increased globally from under 7% in 2005 to 62% in 2018. There have been successes in increasing ART coverage in all populations and locations. However, progress varies by population and location in many regions. There is inequity in ART coverage: women (68%) versus men (55%), and adults (62%) versus children (54%). This inequity has widened over time, and with expanded ART eligibility criteria. On the other hand, data from at least one high-burden country (Ethiopia) shows that inequity among regions has narrowed over time due to the improvements in the primary health care systems and implementation of the public health approach in the country.ConclusionART coverage has increased at global, regional and national levels to all population groups. However, the gains have not been equitable among locations and populations. Policies towards universality may widen the inequity in resource-limited settings unless countries take precautions and “put the last first”. We argue that primary health care and public health approaches, with multi-sectoral actions and community engagement, are vital to minimize inequity, achieve UHC and leave no one behind.

Efficacy of Vitamin D for the Prevention of Pulmonary Tuberculosis and Mortality in HIV: A Randomised, Double-Blind, Placebo-Controlled Trial

Background: Observational data suggests that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis (TB) and mortality among people living with HIV; however, the efficacy of vitamin D supplementation remains unknown. Methods: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4,000 HIV-infected adults initiating antiretroviral therapy (ART) with low 25-hydroxyvitamin D (25(OH)D) levels in Dar es Salaam, Tanzania. The vitamin D group received weekly 50,000 IU vitamin D3 supplements for the first month of ART followed by daily 2,000 IU vitamin D3 supplements. The placebo arm received a matching weekly and daily placebo regimen. Findings: A total of 415 deaths were recorded and there was no overall effect of vitamin D3 supplementation on the risk of mortality (hazard ratio (HR): 1·04; 95% CI: 0·85-1·25; p=0·73). However, vitamin D3 supplementation appeared to reduce the risk of death by 41% (0-65%) among participants with baseline pulmonary TB and by 48% (95% CI: 11-69%) among those with WHO HIV Stage IV disease at the time of ART initiation. There was no effect on the overall incidence of pulmonary TB (HR: 0·78; 95% CI: 0·54-1·13; p=0·19), although vitamin D3 was found to reduce the incidence of sputum smear-positive pulmonary TB (HR: 0·54; 95% CI: 0·31-0·92; p=0·03). The vitamin D3 regimen increased serum 25(OH)D (p<0·001) and did not increase the risk of hypercalcemia (p=1·00) as compared to placebo. Interpretation: Vitamin D3 supplementation may improve survival for the subset HIV-infected adults initiating ART with pulmonary TB disease or advanced HIV disease and reduce the incidence of sputum smear positive pulmonary TB. Trial Registration: ClinicalTrials.gov, NCT01798680. Funding Statement: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Declaration of Interests: The authors stated: None to declare. Ethics Approval Statement: The trial protocol was approved by the Harvard T. H. Chan School of Public Health Institutional Review Board, the Tanzanian National Health Research Ethics Sub Committee (NatHREC), and the Tanzania Food and Drug Authority (TFDA) and was overseen by an independent data and safety monitoring board.

Patient factors and immunologic recovery in HIV management

CD4 cells are important component of the body�s defense mechanism, therefore CD4 cells count is an important indicator of immune function. Human immunodeficiency virus infection attacks the CD4 cells in the blood, causing their number to drop. When that happens, the person�s body cannot fight infections effectively. The individual then becomes vulnerable to attack by opportunistic infections. These infections occur more frequently and more severely in persons living with HIV (PLWH) than in the general population.\r\nHighly active antiretroviral therapy (HAART), when adhered to by PLWH, is capable of suppressing HIV viral replication, thereby reducing the viral population to �lower than detectable level� which eventually results in immunologic recovery and restoration of normal immune function as the number of CD4 cells increase to normal range.\r\nHowever, not all PLWH achieve immunologic recovery. There are factors that affect immunologic recovery. This study, with a sample size of 1203 PLWH, was aimed at determining patient factors which could affect immunologic recovery in PLWH on antiretroviral therapy in public health care facilities in KwaZulu-Natal. Data was collected using questionnaire and hospital patient charts. 64% of the participants were female, 45.5% of had immunologic failure (CD4 cell count <200 cells/�L). CD4 cells count outcome was statistically significantly associated with gender, poor adherence to ART and baseline CD4 cells count. The probability of immunologic failure for those who did not strictly adhere to ART was more than 3 folds higher than those who adhered to ART; and the probability of immunologic failure was more than 8 folds higher for those who had baseline CD4 cells <200 cells/�L than those who had baseline CD4 cells ?200 cells/�L. These therefore affirm the absolute necessity of strict adherence to ART by PLWH as well as highlights the necessity of the WHO HIV treatment policy of �test and treat�.\r\nKey words: Patient, Immunologic, CD4, HIV, Factors, Failure, recovery

Adverse Childhood Experiences and HIV Risk Behaviors in Young Adult Afghan Immigrants to Eastern Iran

This study aims to examine the association between separate and accumulative ACEs and migration-associated HIV risk behaviors among Afghan immigrants to Iran. A retrospective survey was conducted in three provinces of Iran. Respondent-driven sampling (RDS) technique recruited a sample of 772 young adult Afghan immigrants aged 18 to 37 years. Data were collected through structured interviews between January and March 2019. ACEs and HIV risk behaviors were measured, respectively, by an adapted version of the WHO Adverse Childhood Experiences InternationalQuestionnaire (ACE-IQ) and HIV Risk-taking Behavior Scale (HRBS). A notable proportion of participants with a mean percentage of 78.3 ± 10.49 reported cumulative ACEs. Only a mean percentage of 5.5 ± 3.18 of participants reported HIV risk behaviors. After adjusting for intra-class correlation (ICC), significantly higher odds of drug-related behaviors were found among respondents who were exposed to family dysfunction during childhood (aOR= 2.53, 95% CI 1.32–3.75) and those who experienced cumulative childhood adversities (aOR= 1.96, 95% CI 1.09–2.83). Respondents with no education (aOR= 1.38, 95% CI 0.85–1.92), those who were exposed to childhood family dysfunction (aOR= 2.10, 95% CI 1.39–2.81), and those who experienced cumulative childhood adversities (aOR= 2.31, 95% CI 1.33–3.29) were more likely to report sexual risk behaviors. Prevention of ACEs and support for Afghan immigrants exposed to ACEs to develop resilience are essential to improving the HIV health of young adults in future generations. Cumulative ACEs and, separately, family dysfunction, are overlapping risk factors for HIV risk behaviors in young adult Afghan immigrants

The HIV treatment cascade in people living with HIV in Iran in 2014: Mixed-method study to measure losses and reasons.

The study assessed the HIV treatment cascade of people living with HIV (PLWH) in Iran and the reasons for gaps in HIV services in 2014. We did the cascade analysis using the WHO HIV test–treat–retain cascade analysis tool (2014). To measure the gaps, we checked the records for all PLWH reported to the national HIV surveillance till September 2014 to define how many were alive, linked to HIV care, assessed for CD4 cell count, started antiretroviral therapy (ART), and reported to be alive up to five years after ART. To assess the reasons for gaps in the cascade, we ran desk review, four focus group discussions and 51 in-depth interviews with key informants including PLWH. Spectrum model estimated 75,700 PLWH in Iran, of whom only 22,647 people (%30) were diagnosed. Of those who were diagnosed with HIV, 16,266 people (%72) had enrolled in HIV care. About 13% of all PLWH were retained in HIV care and only 9% (6745 people) had ever been tested for CD4 cell count. Only 8% (6018 people) of all PLWH had received ART by September 2014. We found the biggest gap in the HIV treatment cascade to be HIV diagnosis as only 30% of PLWH have been diagnosed. Innovative strategies to improve HIV testing, particularly those that work best for key populations, are critical to reach the 90–90-90 targets.

Urine lipoarabinomannan (LAM) and antimicrobial usage in seriously-ill HIV-infected patients with sputum smear-negative pulmonary tuberculosis.

Based on current WHO guidelines, hospitalized tuberculosis (TB) and HIV co-infected patients with CD4 count <100 cells/mm3 who are urine lipoarabinomannan (LAM) positive should be initiated on TB treatment. This recommendation is conditional, and data are limited in sputum smear-negative patients from TB endemic countries where the LAM test is largely inaccessible. Other potential benefits of LAM, including reduction in antibiotic usage have, hitherto, not been explored. We consecutively enrolled newly-admitted seriously-ill HIV-infected patients (n=187) with suspected TB from three hospitals in KwaZulu-Natal, South Africa. All patients were empirically treated for TB as per the WHO 2007 smear-negative TB algorithm (patients untreated for TB were not recruited). Bio-banked urine, donated prior to anti-TB treatment, was tested for TB-infection using a commercially available LAM-ELISA test. TB sputum and blood cultures were performed. Data from 156 patients containing CD4 count, urine-LAM, sputum and blood culture results were analysed. Mean age was 37 years, median CD4-count was 75 cells/mm3 [interquartile range (IQR), 34-169 cells/mm3], 54/156 (34.6%) were sputum culture-positive, 12/54 (22.2%) blood-culture positive, and 53/156 (34.0%) LAM-positive. Thus, LAM sensitivity was 55.6% (30/54). The study design did not allow for calculation of specificity. Urine-LAM positivity was associated with low CD4 count (P=0.002). Ninety-point-six percent (48/53) of LAM-positive patients received antibiotics [15/48 (31.3%), 23/48 (47.9%) and 10/48 (20.8%) received one, two or three different antibiotics respectively], while the duration of antibiotic therapy was more than 5 days in 26 of 46 (56.5%) patients. Urine LAM testing in sputum smear-negative severely-ill hospitalized patients with TB-HIV co-infection and advanced immunosuppression, offered an immediate rule-in diagnosis in one-third of empirically treated patients. Moreover, LAM, by providing a rapid alternative diagnosis, could potentially reduce antibiotic overusage in such patients thereby reducing health-care costs and facilitating antibiotic stewardship.