Start Of Antiretroviral Therapy Research Articles

SEARCH Human Immunodeficiency Virus (HIV) Streamlined Treatment Intervention Reduces Mortality at a Population Level in Men With Low CD4 Counts.

We tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing. In the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk. Among 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P < .001). Mortality was reduced substantially more among men (RR = 0.61; 95% CI: .43, .86; P = .01) than among women (RR = 0.90; 95% CI: .62, 1.32; P = .58). After population-based HIV testing, streamlined care reduced population-level mortality among persons with HIV and CD4 ≤ 350/uL, particularly among men. Streamlined HIV care models may play a key role in global efforts to reduce AIDS deaths.

Incidence and predictors of early loss to follow up among patients initiated on protease inhibitor-based second-line antiretroviral therapy in southwestern Uganda

BackgroundGood adherence to antiretroviral therapy (ART) and retention in care are essential for the effectiveness of an HIV care program. With the current increase in numbers of people living with HIV taking second-line ART in sub-Saharan Africa, there is a need to establish their treatment outcomes and the rate of loss to follow up. In this study, we determined the incidence and predictors of loss to follow up among patients taking second-line ART at an experienced HIV treatment center in southwestern Uganda.MethodsThis was a retrospective review of an electronic database at Mbarara Regional Referral Hospital HIV clinic in southwestern Uganda. Second-line ART included at least two of the nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Loss to follow-up was defined as failure to return to the health facility for care or treatment refill for 180 days or more from the previous visit. After excluding children less than 15 years, we pooled data that included socio-demographic, clinical, and laboratory data for patients who started second-line ART between 2002 and 2017. Multiple imputation was done for variables with missing data. Variables that had a p < 0.05 in unadjusted bivariate analyses were included in a multivariate binomial regression model using a stepwise backward selection procedure to describe the factors that independently predicted loss to follow-up.ResultsBetween 2002 and 2017, 1121 patients had been initiated on second-line ART. We included data from 924 participants and of these, 518 (56.1%) were female, the mean age (SD) was 38.4 (± 10.5) years, and 433 (52.4%) had a CD4 count less than 100 cells/µl at the start of second-line ART. The incidence of loss to follow-up was 26.7 per 100 person-years. Male gender (Adjusted risk ratio (ARR) = 1.8, 95% CI 1.5–2.0) p < 0.001 and anemia ARR 1.4, 95% CI 1.1–1.6) p < 0.001 were strongly associated with loss to follow up.ConclusionsThere is a high incidence of loss to follow up among patients taking protease-inhibitor based second-line ART at a tertiary HIV center in southwestern Uganda. There is a need to routinely measure hemoglobin during clinic reviews, and establish mechanisms to retain males initiated on second-line ART in care. The association of anemia and loss to follow up needs to be investigated.

Antiretroviral Therapy Anchor-based Trends in Body Mass Index Following Treatment Initiation Among Military Personnel with HIV.

Weight gain and obesity in people living with HIV have been associated with increased risk for non-AIDS-related comorbidities, and integrase strand transfer inhibitor (INSTI)-based regimens may lead to comparatively more weight gain than other regimens. We evaluated body mass index (BMI) following antiretroviral therapy (ART) initiation among participants in the U.S. Military HIV Natural History Study (NHS). NHS participants with available baseline weight and height data initiating ART from 2006 to 2017 were considered for analysis. Antiretroviral therapy was categorized by anchor class to include INSTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Linear growth-curve modeling was used to predict BMI changes from ART initiation through 2 years of follow-up in participants stratified by baseline BMI (<25 vs ≥25 kg/m2) at ART start and anchor drug class. These models were adjusted for demographic- and HIV-related characteristics. Of 961 NHS participants started on initial ART between 2006 and 2017, 491 men who had available baseline BMI data and were virally suppressed (<200 c/mL) at 1 and 2 years of follow-up were included. Overall, the predicted BMI increased at each time point over 2 years regardless of baseline BMI. There was a trend toward less weight gain for non-INSTI regimens regardless of demographic- or HIV-related factors (-0.65 kg/m2/yr, P = .070). In participants with BMI <25, all regimens were associated with BMI gains except in those with high viral load (≥100,000 copies/mL) started on PI regimens (-1.91 kg/m2/yr, P = .000; n = 13). For those participants with BMI ≥25, only INSTI- and PI-based regimens were significantly associated with increased BMI (INSTI 0.54 kg/m2/y, P = .000; PI 0.39 kg/m2/yr, P = .006). Non-nucleoside reverse transcriptase inhibitors were not associated with weight gain regardless of race- or HIV-related characteristics. African Americans with BMI ≥25 were more likely to gain weight as compared to Whites (0.99 kg/m2/yr, P = .016). Specific anchor drug-based predictions revealed that only INSTI use among African Americans was significantly associated with BMI gains (1.85 kg/m2/yr, P = .007); NNRTI- and PI-related weight change was not significant as compared to Whites. In our cohort of young military members with HIV infection, those with BMI <25 experienced BMI gains across all ART classes. Among those with BMI ≥25, African Americans on INSTI regimens had the greatest BMI gains. Further studies are needed to determine whether NNRTI regimens should be considered in certain individuals at risk for INSTI-associated weight gain.

Antiretroviral treatment initiation among HIV-positive participants in the Bangkok men who have sex with men cohort study, 2006-2016.

Data on HIV antiretroviral therapy (ART) initiation among key-affected populations will support reaching the UNAIDS goal to end AIDS by 2030. We assessed ART initiation among HIV-positive participants of the Bangkok Men Who Have Sex with Men (MSM) Cohort Study, which enrolled sexually experienced MSM aged ≥ 18 years and included visits every four months for a period of 3-5 years, from 2006-2016. At each visit, participants had HIV testing and completed computer-assisted self-interviewing on demographics and HIV risk behaviors. If they acquired HIV infection during the study, they received active referral for HIV treatment, continued in the cohort, and were asked about ART initiation. We used logistic regression to determine factors associated with ART initiation. Overall, 632 (36.2%) participants were diagnosed with HIV infection; 463 (73%) had a follow-up visit reporting information about ART, of those 346 (74%) reported ART initiation, with 323 (93%) on ART initiating ART through their registered national health benefit program. Only 70 (11%) were eligible for ART at time of diagnosis, and 52 (74%) initiated ART, on average, within six months of diagnosis. Multivariable analysis evaluating factors associated with ART initiation demonstrated that low CD4 cell count at time of diagnosis was the only independent factor associated with ART initiation. Most HIV-positive participants in the cohort reported ART initiation through the national health benefit program but limited data suggests there could be improvements in length of time to initiation of ART. Efforts should focus on ART start in MSM and transgender women soon after HIV diagnosis.

Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients

It has been reported that hepatic flare (HF), attributable to the development of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected patients, occurs frequently after the start of anti-retroviral therapy (ART). We have observed several cases of hepatitis B surface antigen (HBsAg) loss after IRIS. However, the factors leading to HBsAg clearance remain unknown. We measured CD4+ and CD8+ T cells, cytokines and chemokines in 16 patients coinfected HIV-1 and HBV with IRIS, and analyzed the factors leading to HBsAg clearance after IRIS. There was no significant difference in the CD4+ and CD8+ T cell counts between the HBsAg clearance and non-clearance groups, while the serum concentrations of almost all cytokines and chemokines in the HBsAg clearance group were higher than in the HBsAg non-clearance group at any time of observation. In particular, IP-10 at the ALT peak, GM-CSF and IL-12 one month after the ALT peak and TNF-α and GM-CSF after the ALT concentrations fell to within normal limits, were significantly higher in the HBsAg clearance group. It seems that HBsAg loss after IRIS requires continued immune responses against HBV, involving Th1 cytokines.

HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda.

BackgroundOral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP.Methods and findingsDuring population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning–based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score–matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15–24 years; 19% in serodifferent partnerships), of whom 79% engaged in ≥1 follow-up visit and 61% self-reported PrEP adherence at ≥1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22–0.49) among PrEP initiators. Among matched controls, HIV incidence was 0.92 per 100 person-years (95% CI 0.49–1.41), corresponding to 74% lower incidence among PrEP initiators compared to matched controls (adjusted incidence rate ratio [aIRR] 0.26, 95% CI 0.09–0.75; p = 0.013). Among women, HIV incidence was 76% lower among PrEP initiators versus matched controls (aIRR 0.24, 95% CI 0.07–0.79; p = 0.019); among men, HIV incidence was 40% lower, but not significantly so (aIRR 0.60, 95% CI 0.12–3.05; p = 0.54). Of 25 participants with incident HIV infection (68% women), 7/25 (28%) reported taking PrEP ≤30 days before HIV diagnosis, and 24/25 (96%) started ART. Of those with repeat HIV RNA after ART start, 18/19 (95%) had <1,000 c/ml. One participant with viral non-suppression was found to have transmitted viral resistance, as well as emtricitabine resistance possibly related to PrEP use. Limitations include the lack of contemporaneous controls to assess HIV incidence without PrEP and that plasma samples were not archived to assess for baseline acute infection.ConclusionsPopulation-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls prior to PrEP availability. HIV infections were significantly lower among women who started PrEP. Universal HIV testing with linkage to treatment and prevention, including PrEP, is a promising approach to accelerate reductions in new infections in generalized epidemic settings.Trial registrationClinicalTrials.gov NCT01864603.

Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.

Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with non-perinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence. A retrospective cohort study. We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004-2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs. We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex. As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.

Influencing Factors of Mortality Among Adult HIV Patients Under Antiretroviral Therapy: The Case of Hossana Queen Elleni Mohammad Memorial Hospital, Ethiopia

Even though the use of ART has brought a significant reduction in the mortality and morbidity of patients living with HIV/AIDS globally, still a number of patients die after the start of Antiretroviral Therapy. This study aimed at identifying influencing factors of mortality among adult HIV infected patients who are on ART in Hossana Queen Elleni Mohammad Memorial Hospital. The data for the study were obtained from Hossana Queen Elleni Mohammad Memorial Hospital Antiretroviral Therapy clinic. The HIV infected patients ≥ 15 years of age. Binary logistic regression model was applied to analyze the data so as to identify the influencing factors associated with mortality of HIV infected patients. A total of 400 adult HIV infected patients who were under ART were included in the study. Of 400 patients, 18.75% of them died. Age of the patients 40 or above (OR=1.73, 95% CI: 1.13–1.92), primary education (OR=0.29, 95% CI: 0.030–0.71), secondary or above education (OR=0.13, 95% CI: 0.03–0.16), alcohol (OR=3.35, 95% CI: 1.79– 6.27), baseline weight 50 kg or above (OR=0.42, 95% CI: 0.23–0.77), TB positive (OR=3.76, 95% CI: 2.06–6.83), and baseline CD4 200 or above (OR=0.24, 95% CI: 0.19–0.50) were significantly associated with mortality among HIV patients under Antiretroviral Therapy. Health workers need to support those patients with no or little education by continuous awareness creation of taking care of themselves and knowing what factors facilitate death. Furthermore, patients who drink alcohol need to reduce excessive drinking.

Behavioral factors associated with delayed ART initiation among people living with HIV/AIDS (PLWH) in Nekemte referral Hospital, Western Ethiopia

BackgroundDelayed initiation of antiretroviral therapy (ART) continues to drive morbidity, mortality and onward human immune virus (HIV) infection transmission. The major causes for HIV related life threatening events were due to delayed ART initiation. Little has been documented about the timing of ART initiation in hospital settings where majority of patients present with advanced HIV disease and opportunistic infections, with a potentially high risk of mortality after discharge. So early initiation of ART is needed to reduce HIV related morbidity and mortality and to reduce HIV infection transmission, so the study aimed to determine PLWH’s health belief factors related to delayed ART initiation. MethodsA hospital-based cross-sectional study was conducted to explore health-related beliefs among PLWH on delayed ART initiation at ART Clinic, Nekemte Referral hospital, Western Ethiopia between January 1, 2020 and March 31, 2020 for the time period from January 1, 2016 to December 31, 2019. Consecutive sampling method was used to recruit 417 PLWH. Patients were interviewed to obtain socio-demographic data. Relevant medical history was obtained from patients’ chart records. The collected data were processed and analyzed using Epi data version 3.1 and SPSS version 20. Logistic regression models were constructed to identify independently associated behavioral factors with delayed ART initiation. P-value of <0.05 was used to declare the statistical significance. ResultThe mean age of the 417 PLWH was 33.5 (SD±9.8) years. Most (>75%) of them were urban dwellers and attended formal education. A third (34%) of PLWH initiated ART delayed. Poor literacy status was significantly associated with delayed use of ART. Timing of ART initiation had significantly affected by respondents’ perceived threat, perceived net benefit and self-efficacy to start ART there. ConclusionPrevalence of delayed ART initiation was relatively low. Strengthening the mechanisms of early HIV test, linkage to care and awareness on ART benefit are recommended to initiate ART early.

Cumplimiento de los indicadores de proceso en un programa para el manejo de pacientes que viven con VIH/SIDA

Introducción: La infección por VIH/SIDA es un problema de salud pública para el cual se han desarrollado múltiples estrategias de control. Colombia busca estandarizar la atención en centros especializados, bajo las recomendaciones de la Guía de Práctica Clínica vigente y con una intervención multidisciplinaria. Objetivo: Determinar el cumplimiento de los indicadores de gestión en un programa para el manejo de pacientes que viven con VIH/SIDA, en una IPS especializada de Cali, Colombia. Métodos: Se hizo un estudio observacional, descriptivo y retrospectivo en pacientes mayores de 18 años que ingresaron al programa e iniciaron tratamiento antirretroviral, entre enero y diciembre de 2016. Se analizó información de 173 registros clínicos y datos reportados en la Cuenta de Alto Costo de pacientes con diagnóstico de VIH/SIDA. Se evaluaron 13 indicadores del área clínica, todos de proceso; tres de evaluación inicial, dos de monitoreo, seis de terapia y dos de prevención especifica.Resultados: El 23.1% de los indicadores cumplieron la meta establecida por el consenso de la CAC; se identificó cumplimiento del 100% de las recomendaciones en 11% de la población y el 72.8% logró resultados de carga viral indetectable entre la semana 9 y la semana 117 posterior al inicio de tratamiento antirretroviral; el 69.3% reportó supresión viral antes de la semana 48 y se evaluó la carga viral al 1.2% de la población. Conclusión: El cumplimiento de los indicadores de gestión de la guía de práctica clínica (GPC) fue bajo y están relacionados a las barreras administrativas.

Rapid Start of Antiretroviral Therapy in Youth Diagnosed with HIV Infection.

Guidelines for the use of antiretroviral agents in adults and adolescents with HIV recommend that antiretroviral therapy (ART) be started as soon as possible. While rapid initiation of ART in adults with HIV has been well-described, there is relatively little information describing this approach for youth. On April 1, 2018, St. Jude Children's Research Hospital began offering ART to youth with HIV infection at their first clinic visit. We report the results of a quality improvement initiative that compared patients who offered ART at their first visit to a historical cohort of patients who initiated ART at a subsequent visit. Demographic, HIV biomarker, and visit information were abstracted from medical records, described and compared using univariate statistical methods. There were 124 ART-naive youth (median age 19 years, 91% male, 94% black) first seen during the indicated time period. A total of 54 patients were in the baseline cohort and 70 patients were in the rapid start cohort. 90% of youth in the rapid start cohort started ART on their first clinic visit. Time from first clinic visit to undetectable viral load was significantly higher in the baseline cohort compared with the rapid start cohort (median 54 vs. 41 days; P = 0.01). Retention in care 12 months following the first clinic visit was comparable and overall high (>80%). Starting ART-naïve youth with HIV infection on ART at their first clinic visit is feasible, has high acceptance, leads to faster viral load suppression, and is associated with high retention in care.

Gender difference in mortality among pulmonary tuberculosis HIV co-infected adults aged 15-49 years in Kenya.

SettingKenya, 2012–2015ObjectiveTo explore whether there is a gender difference in all-cause mortality among smear positive pulmonary tuberculosis (PTB)/ HIV co-infected patients treated for tuberculosis (TB) between 2012 and 2015 in Kenya.DesignRetrospective cohort of 9,026 smear-positive patients aged 15–49 years. All-cause mortality during TB treatment was the outcome of interest. Time to start of antiretroviral therapy (ART) initiation was considered as a proxy for CD4 cell count. Those who took long to start of ART were assumed to have high CD4 cell count.ResultsOf the 9,026 observations analysed, 4,567(51%) and 4,459(49%) were women and men, respectively. Overall, out of the 9,026 patients, 8,154 (90%) had their treatment outcome as cured, the mean age in years (SD) was 33.3(7.5) and the mean body mass index (SD) was 18.2(3.4). Men were older (30% men’ vs 17% women in those ≥40 years, p = <0.001) and had a lower BMI <18.5 (55.3% men vs 50.6% women, p = <0.001). Men tested later for HIV: 29% (1,317/4,567) of women HIV tested more than 3 months prior to TB treatment, as compared to 20% (912/4,459) men (p<0.001). Mortality was higher in men 11% (471/4,459) compared to women 9% (401/4,567, p = 0.004). There was a 17% reduction in the risk of death among women (adjusted HR 0.83; 95% CI 0.72–0.96; p = 0.013). Survival varied by age-groups, with women having significantly better survival than men, in the age-groups 40 years and over (log-rank p = 0.006).ConclusionWomen with sputum positive PTB/HIV co-infection have a significantly lower risk of all-cause mortality during TB treatment compared to men. Men were older, had lower BMI and tested later for HIV than women.

Nutritional status and other predictors of immune response recovery among HIV-AIDS patients receiving antiretroviral therapy in Dr. Sardjito Hospital, Yogyakarta, Indonesia: a retrospective cohort study

Introduction: Nutritional status and immune response of Human Immunodeficiency Virus-Acquired Immune Deficiency Syndrome (HIV-AIDS) patients are closely connected. There are limited studies assessing the influence of Body Mass Index (BMI) on immune response recovery among HIV patients in Indonesia. This study aimed to identify the BMI and other predictors of immune response recovery among HIV-AIDS patients following two years of Antiretroviral (ARV) therapy. Methods: This research was a retrospective cohort study among HIV-AIDS patients who started ARV therapy from January 2014 to December 2016 at Dr. Sardjito Hospital, Yogyakarta. Data were collected from ARV registry and medical reports. Data were analysed using linear regression. Results: A total of 255 patients were included in the study, with a median BMI of 20.07 kg/m2. Results showed that BMI was not significantly correlated with immune response recovery at the 6th, 12th, 18th, and 24th months of ARV therapy (p&gt;0.05). But, the increase in cluster of differentiation 4 (CD4) cell count was higher in overweight and pre-obese patients than underweight patients, especially in the 18th and 24th months of therapy. Factors related to immune response recovery were the regularity of treatment at the 12th, 18th, and 24th months of ARV therapy, and the use of Tenofovir at 18th-month therapy (p&lt;0.05). Conclusion: Immune response recovery was higher in overweight and pre-obese patients. Using Tenofovir type ARV and doing treatment regularly can increase CD4 cell counts. Underweight patients need to enhance their nutritional status to improve their immune response during ARV therapy.

Evaluation of Prognostic response in HIV positive patients after Antiretroviral Therapy

Objective: The present study was aimed to monitor the prognostic response of antiretroviral therapy in HIV positive patients.&#x0D; Methodology: The study was conducted on confirmed HIV positive patients registered at HIV treatment and care centre, PIMS. Islamabad from January 2013 to December 2015.. Among all HIV positive patients,276 adult cases were selected. There were 263 patients on first-line antiretroviral (ARV) therapy and 13 patients were shifted to 2nd line ARV therapy.CD4 cell counts and viral load (Polymerase chain reaction) monitoring was done after one year of starting ARV therapy.&#x0D; Results: Out of 276 adult patients, 75%(n=207) were male and 25%(n=69) were females. Among 276 adult cases, 95.3% (n=263) patients were on first line ARV therapy. Patients on first line ARV therapy showed good prognostic response. There were 15.5%(n=40) patients having CD4+cells less than 350cells/µL. There were 84.5%(n=223) patients having CD4 +cells count greater than 350cells/µL There were 69%(n=182) patients having viral load &lt;50copies/ml and 31%(n=81) patients who had viral load &gt;50copies/ml.&#x0D; Conclusion: First line ARV therapy given to HIV positive patients proved itself best both in respect of increasing the immunity of HIV positive patients by increasing the number of CD4 cells and also results in effective viral load suppression.

Incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy in public hospitals of Northern Ethiopia: Multicenter retrospective study.

BackgroundThis study aimed to determine the incidence and factors associated with treatment failure among HIV infected adolescent and adult patients on second-line antiretroviral therapy (ART) in public hospitals of Northern Ethiopia.MethodsA retrospective study was conducted from September 1, 2007 to July 30, 2017 on 227 patients. The data were extracted using a retrieval checklist from the patient’s charts. The incidence rate of treatment failure was calculated using Kaplan–Meier methods and Cox proportional hazard model was used to assess factors associated with treatment failure.ResultThe study subjects were followed for a total observation of 788.58 person-years with a median follow-up period of 35 (IQR: 17–60) months after switching to second-line ART. About 57 (25.11%) patients developed treatment failure, out of which, 32 (56.14%) occurred during the first two years. The overall incidence of second-line treatment failure was 72.3 per 1000 person years (95%CI: 55.75–93.71) of observation. The Kaplan–Meier estimates of cumulative treatment failure after 1, 2, and around 10 years of follow-up were 12.31% (95%CI: 8.60–17.45%), 14.99% (95%CI: 10.82%-20.57%), and 48.67% (95%CI: 32.45–67.81%) respectively. Age >45 years AHR = 3.33, 95%CI = 1.33–8.31), WHO stage IV (AHR = 3.63, 95%CI = 1.72–7.67), CD4 count <100 cells/mm3 (AHR = 3.79, 95%CI = 1.61–8.91), TB co-morbidity (AHR = 3.39 95%CI = 1.91–6.01) and poor adherence level (AHR = 3.63, 95% CI = 1.89–6.96) at the start of second line ART were significantly associated with second-line ART failure.ConclusionIncidence of second-line ART treatment failure in the first 2 years of follow-up was high. The rate of second-line ART failure was higher in patients who started second-line ART with poor drug adherence, CD4 count <100 cells/mm3, TB co-morbidity, age >45 years, and being in WHO stage IV. Therefore, intensive counseling and adherence support should be given along with strong TB screening. Moreover, the government of Ethiopia should consider endorsing third-line ART drugs after careful cost–benefit analysis.

Transmitted drug resistance to NRTIs and risk of virological failure in naïve patients treated with integrase inhibitors.

Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads >50 HIV-1 RNA copies/mL or a single viral load ≥200 copies/mL after 3months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P=0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P=0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

Rapid ART start in early HIV infection: Time to viral load suppression and retention in care in a London cohort.

Rapid antiretroviral therapy (ART) initiation is recommended in early HIV infection (EHI), even in the absence of baseline viral resistance test result. We analysed time to viral suppression according to ART regimen started in a cohort of patients diagnosed with EHI. Clinical records of individuals consecutively diagnosed with EHI between July 2016-June 2018 were reviewed. The distribution of clinical, virological and immunological factors was compared in treatment groups using the Mann-Whitney U-test. 262 individuals (97% MSM) were diagnosed with EHI. 58% of patients agreed to start ART within 14 days of diagnosis. Tenofovir-based combinations were prescribed to all patients. DRV/b was the most commonly prescribed third agent (78%), when genotypic resistance testing was not available at time of ART choice. Switching to INSTI was encouraged once VRT became available and 27% switched from DRV/b to INSTI (mainly RAL) within 28 days from ART start. Those receiving INSTI were more likely to have a baseline viral load exceeding 1 million HIV-1 RNA copies/mL compared with those starting with DRV/b. Rapid start with INSTI regimens resulted in quicker viral suppression than when DRV/b was chosen in EHI, even when that was subsequently switched to INSTI. Retention in care following rapid ART start was achieved by all patients at 24 weeks. Starting an INSTI-based ART combination was associated with quicker viral suppression than when a protease inhibitor-based combination was chosen. No differences in the achievement of viral suppression or in retention in care were observed.

Prevalence of and Risk Factors for Low Free Testosterone Levels in Japanese Men with Well-controlled Human Immunodeficiency Virus Infection.

The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurate indicator. We also determined the relationship between age and fTST levels and identified risk factors for hypogonadism in men with HIV infection. We retrospectively reviewed fTST levels and associated clinical factors in 71 wellcontrolled HIV-infected men who were treated at Teikyo University Hospital between April 2015 and March 2016 and who had data available on serum fTST levels, measured >6 months after starting antiretroviral therapy. fTST was measured using radioimmunoassay on blood samples collected in the morning. Risk factors for hypogonadism were identified using Welch's t-test and multiple regression analysis. The men had a mean (± standard deviation) age of 47.4 ± 13.6 years, and mean (± standard deviation) serum fTST level of 13.0 ± 6.1 pg/mL. Fifteen (21.1%) men had hypogonadism based on a fTST <8.5 pg/mL. Serum fTST levels significantly decreased with age (-0.216 pg/mL/year). Older age and low hemoglobin levels were identified as risk factors for hypogonadism. The men in the study experienced a more rapid decline in fTST levels with age than men in the general population (-0.161 pg/mL/year). Serum fTST levels in men with HIV infection should be monitored, especially in older men and those with low hemoglobin levels.

Evaluation of the impact of delayed centrifugation on the diagnostic performance of serum creatinine as a baseline measure of renal function before antiretroviral treatment.

BackgroundThe measurement of serum creatinine is a standard requirement of the medical management of people living with HIV. Renal dysfunction is common, both as a complication of HIV-infection and as a result of its treatment. The detection of abnormal renal function before the start of antiretroviral therapy will impact patient management and the outcome of treatment.ObjectivesThis study aimed to determine if a time delay in the centrifugation of serum samples affected the creatinine level and the estimated glomerular filtration rate as recorded on the analytical platforms used in the laboratory.MethodsTwenty-two (n = 22) HIV-positive, newly diagnosed and treatment-naïve patients were randomly recruited from Alexandra Health Clinic, Johannesburg, South Africa. Serum samples were centrifuged at six time intervals following receipt of the sample viz. < 4 h (baseline), 6 h, 24 h, 48 h, 72 h and 96 h. Creatinine concentrations were measured on the Roche platform utilising the enzymatic and kinetic Jaffe methods. Whole blood samples were also analysed with the Abbott i-STAT point-of-care instrument. The estimated glomerular filtration rate was calculated using the Cockcroft Gault, CKD–Epidemiology Collaboration and Modified Diet and Renal Disease v3/4 equations.ResultsAt baseline (< 4 h) there was good agreement between the enzymatic and kinetic Jaffe methods: bias 1.7 µmol/l. The enzymatic and i-STAT creatinine concentrations were stable over 96 h viz. changes of 1.8% and 5.7%. However, from 24 h onwards agreement between the enzymatic and kinetic Jaffe methods was poor with the latter measuring 43.7 µmol/l higher than the enzymatic method at 96 h. Creatinine concentrations measured with the kinetic Jaffe method increased significantly in samples centrifuged after 6 h (p < 0.001, 61.7% change), and resulted in a 95% decline in eGFR at 96 h as determined with the CKD–Epidemiology Collaboration equation.ConclusionThe analysis of serum creatinine using the isotope dilution mass spectrometry traceable kinetic Jaffe method is unreliable if performed on samples centrifuged ≥ 6 h after collection. The raised creatinine concentration can affect clinical decisions such as renal functional assessment, choice of antiretroviral drug or regimen, and the dose and frequency of medication.

Early ART in Acute HIV-1 Infection: Impact on the B-Cell Compartment.

HIV-1 infection induces B cell defects, not fully recovered upon antiretroviral therapy (ART). Acute infection and the early start of ART provide unique settings to address the impact of HIV on the B cell compartment. We took advantage of a cohort of 21 seroconverters, grouped according to the presence of severe manifestations likely mediated by antibodies or immune complexes, such as Guillain-Barré syndrome and autoimmune thrombocytopenic purpura, with a follow-up of 8 weeks upon effective ART. We combined B and T cell phenotyping with serum immunoglobulin level measurement and quantification of sj-KRECs and ΔB to estimate bone marrow output and peripheral proliferative history of B cells, respectively. We observed marked B cell disturbances, notably a significant expansion of cells expressing low levels of CD21, in parallel with markers of both impaired bone marrow output and increased peripheral B cell proliferation. This B cell dysregulation is likely to contribute to the severe immune-mediated conditions, as attested by the higher serum IgG and the reduced levels of sj-KRECs with increased ΔB in these individuals as compared to those patients with mild disease. Nevertheless, upon starting ART, the dynamic of B cell recovery was not distinct in the two groups, featuring both persistent alterations by week 8. Overall, we showed for the first time that acute HIV-1 infection is associated with decreased bone marrow B cell output assessed by sj-KRECs. Our study emphasizes the need to intervene in both bone marrow and peripheral responses to facilitate B cell recovery during acute HIV-1 infection.