Timing Of Antiretroviral Treatment Initiation Research Articles

Antigen specificities and proviral integration sites differ in HIV-infected cells by timing of antiretroviral treatment initiation.

Despite effective antiretroviral therapy (ART), persons living with HIV (PWH) harbor reservoirs of persistently infected CD4+ cells, which constitute a barrier to cure. Initiation of ART during acute infection reduces the size of the HIV reservoir, and we hypothesized that in addition, it would favor integration of proviruses in HIV-specific CD4+ T cells, while initiation of ART during chronic HIV infection would favor relatively more proviruses in herpesvirus-specific cells. We further hypothesized that proviruses in acute-ART-initiators would be integrated into antiviral genes, whereas integration sites in chronic-ART-initiators would favor genes associated with cell proliferation and exhaustion. We found the HIV DNA distribution across HIV-specific vs. herpesvirus-specific CD4+ T cells was as hypothesized. HIV integration sites (IS) in acute-ART-initiators were significantly enriched in gene sets controlling lipid metabolism and HIF-1α-mediated hypoxia, both metabolic pathways active in early HIV infection. Persistence of these infected cells during prolonged ART suggests a survival advantage. IS in chronic-ART-initiators were enriched in a gene set controlling EZH2 histone methylation; and methylation has been associated with diminished LTR transcription. These differences we found in antigen specificities and IS distributions within HIV-infected cells might be leveraged in designing cure strategies tailored to the timing of ART initiation.

Characterization and Determinants of Long-Term Immune Recovery Under Suppressive Antiretroviral Therapy.

We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia. Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in people living with HIV on ART for at least 8 years by fitting nonlinear mixed-effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed. Overall, our population showed good immune recovery (median plateau [interquartile range]-CD4: 718 [555-900] cells/μL, CD8: 709 [547-893] cells/μL, CD4/CD8: 1.01 [0.76-1.37]). The following factors were predictive of recovery: age, sex, nadir/zenith value, pre-ART HIV-1 viral load, hepatitis C, ethnicity, acquisition risk, and timing of ART initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4 and CD8 cell recovery dynamics: Compared with carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3%-18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using predictors derived from the recovery dynamics improved most model fits. We described and validated a method to characterize individual immune recovery trajectories of people living with HIV on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia.

Does HIV index testing bring patients into treatment at earlier stages of HIV disease? Results from a retrospective study in Ukraine.

Over one-third of people living with HIV (PLH) in Ukraine are not on treatment. Index testing services, which link potentially exposed partners (named partners) of known PLH (index patients) with testing and treatment services, are being scaled in Ukraine and could potentially close this gap. This retrospective study included patient data from 14,554 adult PLH who initiated antiretroviral treatment (ART) between October 2018 and May 2021 at one of 35 facilities participating in an intervention to strengthen index testing services. Mixed effects modified Poisson models were used to assess differences between named partners and other ART initiators, and an interrupted time series (ITS) analysis was used to assess changes in ART initiation over time. Compared to other ART initiators, named partners were significantly less likely to have a confirmed TB diagnosis (aRR = 0.56, 95% CI = 0.40, 0.77, p < 0.001), a CD4 count less than 200 cells/mm3 (aRR = 0.84, 95% CI = 0.73, 0.97, p = 0.017), or be categorized as WHO HIV stage 4 (aRR = 0.68, 9% CI = 0.55, 0.83, p < 0.001) at the time of ART initiation, and were significantly more likely to initiate ART within seven days of testing for HIV (aRR = 1.36, 95% CI = 1.22, 1.50, p < 0.001). Our ITS analysis showed a modest 2.34% (95% CI = 0.26%, 4.38%; p = 0.028) month-on-month reduction in mean ART initiations comparing the post-intervention period to the pre-intervention period, although these results were likely confounded by the COVID epidemic. Our findings suggest that index testing services may be beneficial in bringing PLH into treatment at an earlier stage of HIV disease and decreasing delays between HIV testing and ART initiation, potentially improving patient outcomes and retention in the HIV care cascade.

Therapeutic effectiveness on early and delayed treatment of antiretroviral in TB-HIV patients: a literature review

Introduction: Indonesia is one of the countries with a high TB-HIV prevalence. Antiretroviral treatment (ART) is only being administered to approximately 42% of TB-HIV patients. The low utilization of ART can be attributed, in part, to the delayed initiation of treatment. Nonetheless, starting ART in these people at an early stage poses risks, owing to the increased likelihood of drug-drug interactions and the manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS) side effects when combined with anti-TB medication. Postponing ART, on the other hand, can hasten illness progression and increase the risk of death. Methods: A literature review was conducted to assess the effects of early ART (within four weeks of getting anti-TB) against delayed ART initiation (at least eight weeks after receiving anti-TB) in individuals co-infected with TB and HIV. The data was obtained by a comprehensive electronic search using the PubMed and Science Direct databases. Results: The findings of our study suggest that there was no statistically significant disparity in mortality rates between the early ART group and the delayed ART group. The initial ART cohort had a markedly elevated susceptibility to encountering an IRIS occurrence, particularly among individuals with a CD4 count below 50 cells per cubic millimeter. Conclusion: In summary, the strategy of delaying the initiation of ART in patients co-infected with TB-HIV is seen as preferable when compared to the approach of early treatment. The frequency of IRIS events is a significant determinant in determining the optimal timing of ART initiation in individuals co-infected with TB-HIV.

Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens.

To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.

Cortical and trabecular bone deficit in middle-aged men living with HIV.

A significant increase in risk of hip fracture was observed in middle-aged men living with human immunodeficiency virus (MLWH), almost a decade earlier than those without infection. Data regarding cortical and trabecular bone deficit of hip, an important determinant of bone strength, in MLWH are limited. Quantitative computed tomography was performed in consecutive MLWH aged ≥30 years between November 2017 and October 2018 at Severance Hospital, Seoul, Korea. Volumetric bone mineral density (vBMD) and cortical bone mapping parameters of hip (cortical thickness, CTh; cortical bone vBMD, CBMD; cortical mass surface density, CMSD; endocortical trabecular density, ECTD) were compared to age- and body mass index (BMI)-matched controls (1:2), using a community-based healthy adults' cohort. Among 83 MLWH and 166 controls (mean age: 47.2 years; BMI: 23.6 kg/m2 ), MLWH had lower total hip vBMD (280 ± 41 vs. 296 ± 41 mg/cm3 ), CMSD (155 vs. 160 mg/cm2 ), and ECTD (158 vs. 175 mg/cm3 ) than controls that remained robust after adjustment for covariates (adjusted β: total hip vBMD, -18.8; CMSD, -7.3; ECTD, -18.0; p < 0.05 for all). Cortical bone mapping revealed localized deficit of CTh, CBMD, and CMSD in anterolateral trochanteric region and femoral neck in MLWH compared to controls, with more extensive ECTD deficit. In MLWH, lower CD4 T cell count (/100 cells/mm3 decrement) and protease inhibitor (PI)-based regimen (versus non-PI regimen) at the time of antiretroviral treatment initiation were associated with lower total hip vBMD (adjusted β -7.5 for lower CD4 count; -28.3 for PI-based regimen) and CMSD (adjusted β -2.6 for lower CD4 count; -12.7 for PI-based regimen; p < 0.05 for all) after adjustment for covariates including age, BMI, smoking, alcohol use, HCV co-infection, tenofovir exposure, and CT scanners types. MLWH had lower hip bone density with cortical and trabecular bone deficit compared to community-dwelling controls. This article is protected by copyright. All rights reserved.

Trends and factors associated with initiation of HIV treatment among PLHIV in Jamaica, 2015-2019.

Jamaica did not achieve the UNAIDS 90-90-90 targets in 2020. This study aimed to examine trends and factors associated with uptake of HIV treatment among people living with HIV (PLHIV) in Jamaica and to assess the effectiveness of revised treatment guidelines. This secondary analysis used patient-level data from the National Treatment Service Information System. The baseline sample was 8147 PLHIV initiating anti-retroviral treatment (ART) between January 2015-December 2019. Descriptive statistics were used to summarize demographic and clinical variables and the primary outcome timing of ART initiation. Multivariable logistic regression was used to assess factors associated with ART initiation (same day vs 31+ days), using categorical variables for age group, sex and regional health authority. Adjusted odds ratios and 95% confidence intervals are reported. Most persons initiated ART at 31+ days (n = 3666, 45%) after the first clinic date or on the same day (n = 3461, 43%). Same day ART initiation increased from 37% to 51% over 5 years and was significantly associated with males (aOR = 0.82, CI = 0.74-0.92), 2018 (aOR = 0.66, CI = 0.56-0.77), 2019 (aOR = 0.77, CI = 0.65-0.92). late HIV diagnosis (aOR = 0.3, CI = 0.27-0.33) and viral suppression at the first viral load test (aOR = 0.6, CI = 0.53-0.67). ART initiation at 31+days was associated with 2015 (aOR = 1.21, CI = 1.01-1.45) and 2016 (aOR = 1.30, CI = 1.10-1.53) compared to 2017. Our study shows that same day ART initiation increased between 2015-2019, however it remains too low. Same day initiation was associated with the years after Treat All implementation and late initiation before Treat All, providing evidence of the strategy's success. In order to achieve the UNAIDS targets, there is a need to also increase the number of diagnosed PLHIV retained on treatment in Jamaica. Further studies should be conducted to understand important challenges to accessing treatment as well as differentiated care models to improve treatment uptake and retention.

Gestational weight gain in persons with HIV in the United States.

We evaluated gestational weight gain (GWG) in pregnant persons with HIV (PWH) enrolled in the Surveillance Monitoring for ART Toxicities study. This was a cohort study. GWG was classified as excessive, adequate, or inadequate; weekly GWG in second and third trimesters was calculated using National Academy of Medicine standards. Adjusted modified Poisson and linear regression models were fit with generalized estimating equations to assess the association of antiretroviral treatment (ART) with GWG outcomes stratified by timing of ART initiation [at conception (ART-C) and initiating during pregnancy (ART-I)]. We included 1477 pregnancies (847 ART-C, 630 ART-I) from 1282 PWH. The proportion of excessive, adequate, and inadequate GWG was 44, 24, and 32%, respectively. No associations of ART class with excessive GWG were observed overall. However, among ART-I pregnancies with overweight prepregnancy BMI-based, protease inhibitor-based, nonnucleoside reverse transcriptase inhibitor-based, and nucleoside reverse transcriptase inhibitor-based ART were associated with significantly lower GWG per week than integrase inhibitor (INSTI)-based ART [mean differences: -0.14, -0.27, and -0.29 kg/week, respectively]. Among ART-I pregnancies with obese prepregnancy BMI, lower weekly GWG was also observed for protease inhibitor-based vs. INSTI-based ART (mean difference: -0.14 kg/week). ART class type was not associated with excessive GWG. However, PWH entering pregnancy already overweight/obese and initiating INSTI-based ART had higher weekly GWG in second and third trimesters vs. other ART classes. Further studies to understand how increases in weekly GWG for overweight/obese PWH impinges on long-term maternal/child health are warranted.

The effect of antiretroviral therapy initiation on vitamin D levels and four oral diseases among Kenyan children and adolescents living with HIV.

ObjectivesThe impact of antiretroviral treatment (ART) on the occurrence of oral diseases among children and adolescents living with HIV (CALHIV) is poorly understood. The aim of this study was to determine the effect of ART timing on vitamin D levels and the prevalence of four oral diseases (dry mouth, dental caries, enamel hypoplasia, and non-herpes oral ulcer) among Kenyan CALHIV from two pediatric HIV cohorts.MethodsThis nested cross-sectional study was conducted at the Kenyatta National Hospital, Nairobi, Kenya. CALHIV, 51 with early-ART initiated at <12 months of age and 27 with late-ART initiated between 18 months-12 years of age, were included. Demographics, HIV diagnosis, baseline CD4 and HIV RNA viral load data were extracted from the primary study databases. Community Oral Health Officers performed oral health examinations following standardized training.ResultsAmong 78 CALHIV in the study, median age at the time of the oral examination was 11.4 years old and median ART duration at the time of oral examination was 11 years (IQR: 10.1, 13.4). Mean serum vitamin D level was significantly higher among the early-ART group than the late-ART group (29.5 versus 22.4 ng/mL, p = 0.0002). Children who received early-ART had a 70% reduction in risk of inadequate vitamin D level (<20 ng/mL), compared to those who received late-ART (p = 0.02). Although both groups had similar prevalence of oral diseases overall (early-ART 82.4%; late-ART 85.2%; p = 0.2), there was a trend for higher prevalence of dry mouth (p = 0.1) and dental caries (p = 0.1) in the early versus late ART groups. The prevalence of the four oral diseases was not associated with vitamin D levels (p = 0.583).ConclusionsAfter >10 years of ART, CALHIV with early-ART initiation had higher serum vitamin D levels compared to the late-ART group. The four oral diseases were not significantly associated with timing of ART initiation or serum vitamin D concentrations in this cohort. There was a trend for higher prevalence of dry mouth and dental caries in the early-ART group, probably as side-effects of ART.

Optimal Timing of Antiretroviral Therapy Initiation in Children and Adolescents With Human Immunodeficiency Virus-Associated Pulmonary Tuberculosis.

There is insufficient evidence in children and adolescents with human immunodeficiency virus (CAHIV) to guide the timing of antiretroviral treatment (ART) initiation after starting treatment for pulmonary tuberculosis (pTB). To address this knowledge gap, we evaluated the risk of mortality associated with timing of ART initiation in ART-naive CAHIV treated for pTB. Data were extracted from electronic medical records of ART-naive patients, aged 0-19 years, who were treated for HIV-associated pTB at Baylor Centers of Excellence in Botswana, Eswatini, Malawi, Lesotho, Tanzania, or Uganda between 2013 and 2020. Data were analyzed against a primary outcome of all-cause mortality with unadjusted Kaplan-Meier curves and Cox proportional hazard models. The study population included 774 CAHIV with variable intervals to ART initiation after starting TB treatment: <2 weeks (n = 266), 2 weeks to 2 months (n = 398), >2 months (n = 66), and no ART initiated (n = 44). Adjusted Cox proportional hazards models demonstrated increased mortality 1 year from TB treatment initiation in children never starting ART (adjusted HR [aHR]: 2.67; 95% CI: 1.03, 6.94) versus children initiating ART between 2 weeks and 2 months from TB treatment initiation. Mortality risk did not differ for the <2-weeks group (aHR: 1.02; 95% CI: .55, 1.89) versus the group initiating ART between 2 weeks and 2 months. This retrospective study demonstrated no increase in mortality among CAHIV initiating ART <2 weeks from TB treatment initiation. Given the broad health benefits of ART, this evidence supports the recent WHO recommendation for CAHIV to initiate ART within 2 weeks of initiating TB treatment.

Time of the First Antiretroviral Treatment (ART) Default and Factors Associated to Early ART Default in the Test and Treat Context: Evidence from the West region of Cameroon

Antiretroviral Treatment (ART) retention continues to be a challenge in Sub-Saharan Africa. Understanding factors that contribute to default at the early stage of ART can contribute to avoid poor treatment outcomes. We conducted a retrospective cross-sectional study on adult patients who initiated ART treatment between October 2019 and September 2020 in 25 health facilities in the West region of Cameroon. Early ART default was defined as having default within the first three months of treatment. The mean age of the 2219 clients included in the analysis was 36.8 (SD:13.4), and 838 (36.5%) were male. The median time to the first ART default of the 629 (28.3%) participants who experienced at least one ART default within 12 months after their ART initiation was 5 months, and 41.2% of those defaults occurred within the first three months of ART. Male gender (AOR =1.3; 95%CI:1.1-1.7) and good health at initiation (AOR =1.7; 95%CI:1.3-2.2) were associated with a high risk of early default; while being followed up in a private facility (AOR =0.3; 95%CI:0.2-0.6) were associated with less risk of early default. The ART default at the early stage of HIV care is high in the West region of Cameroon and more frequent in the male gender and in patients with apparent good health at the time of ART initiation. Interventions should be identified and implemented to ensure continuity of ART treatment especially in males, in clients with good health at the time of ART initiation, and in clients on care in public health facilities.

Mental health and initiation of antiretroviral treatment at enrolment into HIV care in Cameroon under a national "treat all" policy: a cross-sectional analysis.

IntroductionRapid antiretroviral treatment (ART) initiation reduces time from HIV infection to viral suppression, decreasing HIV transmission risk. Mental health symptoms may influence timing of ART initiation. This study estimated the prevalence of ART initiation at enrolment into HIV care and the relationship between mental health and ART initiation at enrolment into HIV care.MethodsWe conducted interviews with 426 individuals initiating HIV care in Cameroon between June 2019 and March 2020 to estimate the association between mental health and timing of ART initiation. Depression (Patient Health Questionnaire‐9; cut‐point 10), anxiety (Generalized Anxiety Disorder‐7; cut‐point 10), post‐traumatic stress disorder (PTSD) (PTSD Checklist for DSM‐5; cut‐point 31) and harmful alcohol use (Alcohol Use Disorders Identification Test; cut‐point 16) were dichotomized to represent those with and without each exposure at first HIV care appointment. Date of ART initiation (date ART prescribed) was ascertained from medical records. Separate multivariable log‐binomial regression models were used to estimate the association between mental health exposures and ART initiation at enrolment into care.Results and discussionOverall, 87% initiated ART at enrolment into HIV care. Approximately 20% reported depressive symptoms, 15% reported PTSD symptoms, 12% reported anxiety symptoms and 13% reported harmful alcohol use. In multivariable analyses, individuals with moderate to severe depressive symptoms had 1.7 (95% confidence interval [CI] 1.1, 2.7) times the prevalence of not initiating ART at enrolment into HIV care compared to those with no or mild depressive symptoms. Those with symptoms of PTSD, compared to those without, had 1.9 (95% CI 1.2, 2.9) times the prevalence of not initiating ART at enrolment into HIV care. Symptoms of anxiety or harmful drinking were not associated with ART initiation at enrolment into HIV care in multivariable models.ConclusionsSymptoms of depression and PTSD were associated with lower prevalence of ART initiation at enrolment into HIV care among this sample of individuals initiating HIV care in Cameroon under a “treat all” policy. Research should examine barriers to timely ART initiation, whether incorporating mental health services into HIV care improves timely ART initiation, and whether untreated symptoms of depression and PTSD drive suboptimal HIV care outcomes.

Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients.

Background and PurposeIn TB‐HIV co‐infection, prompt initiation of TB therapy is recommended but anti‐retroviral treatment (ART) is often delayed due to potential drug–drug interactions between rifampicin and efavirenz. In a longitudinal cohort study, we evaluated the effects of efavirenz/rifampicin co‐treatment and time of ART initiation on CYP3A induction.Experimental ApproachTreatment‐naïve TB‐HIV co‐infected patients (n = 102) were randomized to efavirenz‐based‐ART after 4 (n = 69) or 8 weeks (n = 33) of commencing rifampicin‐based anti‐TB therapy. HIV patients without TB (n = 94) receiving efavirenz‐based‐ART only were enrolled as control. Plasma 4β‐hydroxycholesterol/cholesterol (4β‐OHC/Chol) ratio, an endogenous biomarker for CYP3A activity, was determined at baseline, at 4 and 16 weeks of ART.Key ResultsIn patients treated with efavirenz only, median 4β‐OHC/Chol ratios increased from baseline by 269% and 275% after 4 and 16 weeks of ART, respectively. In TB‐HIV patients, rifampicin only therapy for 4 and 8 weeks increased median 4β‐OHC/Chol ratios from baseline by 378% and 576% respectively. After efavirenz/rifampicin co‐treatment, 4β‐OHC/Chol ratios increased by 560% of baseline (4 weeks) and 456% of baseline (16 weeks). Neither time of ART initiation, sex, genotype nor efavirenz plasma concentration were significant predictors of 4β‐OHC/Chol ratios after 4 weeks of efavirenz/rifampicin co‐treatment.Conclusion and ImplicationsRifampicin induced CYP3A more potently than efavirenz, with maximum induction occurring within the first 4 weeks of rifampicin therapy. We provide pharmacological evidence that early (4 weeks) or deferred (8 weeks) ART initiation during anti‐TB therapy has no significant effect on CYP3A induction.LINKED ARTICLESThis article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc

Effect of the Timing of Antiretroviral Treatment Initiation on Outcomes in Children Living With Human Immunodeficiency Virus Admitted With Severe Acute Malnutrition.

Delays in early infant diagnosis and antiretroviral treatment (ART) initiation in developing countries frequently result in malnutrition at initial presentation with associated higher mortality and delayed immune recovery. The optimal timing of ART initiation is yet to be established. Eighty-two children admitted with HIV and severe acute malnutrition (SAM) between July 2012 and December 2015 were enrolled. Patients were randomized to initiate ART within 14 days from admission (early arm) or delay ART initiation until nutritional recovery and >14 days after admission (delayed arm). All patients received a standardized treatment and feeding protocol and were followed to 48 weeks. The mean age of the patients at baseline was 23.3 months (standard deviation [SD], 27.9; range, 1.6-129 months). The mean time from admission to ART initiation was 5.6 days (SD, 4.4) in the early arm and 23 days (SD, 5.8) in the delayed arm (P < .001). There was no significant difference in mortality (P = .62), virologic response (P = .53), and anthropometric response (P = .57) between the 2 groups at 48 weeks. However, the rates of change in CD4, viral load, weight for age z score, and height for age z score occurred earlier and favored the delayed arm at early time points but were not significant at 24 and 48 months. Despite initial improved responses in the delayed arm, lack of difference in outcome at 48 weeks supports a pragmatic approach with earlier ART initiation in children living with HIV admitted with SAM.In this randomised controlled study of ART initiation in children admitted with HIV and severe acute malnutrition (SAM), despite initial improved responses in the delayed arm, lack of difference in outcome at 48 weeks supports a pragmatic approach with earlier ART initiation in children living with HIV admitted with SAM. PACTR 21609001751384.

Effect of HIV-exposure and timing of antiretroviral treatment initiation in children living with HIV on antibody persistence and memory responses to Haemophilus influenzae type b and pneumococcal polysaccharide-protein conjugate vaccines

BackgroundWe investigated the effect of in utero HIV-exposure, timing of antiretroviral treatment (ART) initiation, and ART interruption on memory responses and persistence of immunity induced by pneumococcal (PCV) and Haemophilus influenzae type b (HibCV) polysaccharide-protein conjugate vaccines. MethodsChildren were enrolled (6–12 weeks of age), and vaccinated with a three-dose primary series of 7-valent PCV (PCV7) and HibCV at 6, 10 and 14 weeks of age. Study groups included infants infected with HIV perinatally with CD4+ ≥ 25% initiating ART following immunological or clinical deterioration (ART-Def), or immediately upon enrolment followed by interruption at 40 (ART-Immed/40w) or 96 weeks (ART-Immed/96w); and HIV-uninfected infants with (HEU), and without HIV (HIV-unexpsoed) exposure in utero. Within each group, children were randomized to receive either a booster dose of PCV7 or HibCV at 15 months of age. PCV serotype-specific and polyribosyl ribitol phosphate (PRP) IgG were measured pre-boost, two-weeks post-boost and at two-years of age. Opsonophagocytic activity (OPA) to serotypes 9V, 19F and 23F was measured post-booster dose. ResultsPersistence of IgG to PCV vaccine–serotypes and anti-PRP was similar in all groups of children living with HIV (CLWH) compared to HIV-unexposed children. Anamnestic responses to PCV and HibCV were also similar in all three groups of CLWH compared to HIV-unexposed children. CLWH, however, tended to have lower functional antibody (OPA) titers than HIV-unexposed children after the PCV booster dose for some serotypes. Immunity to PCV and HibCV was similar between the ART-Immed/40w and ART-Immed-96w groups. There were no differences in IgG kinetics between HEU and HIV-unexposed children. ConclusionsA three dose primary series, with or without PCV or HibCV booster doses in CLWH initiated on ART during infancy, would likely be similarly effective in preventing invasive bacterial disease as in HIV-unexposed children.

Combination antiretroviral treatment use in prevention of mother-to-child transmission programmes: 6-week HIV prevalence and relationship to time of antiretroviral treatment initiation and mixed feeding.

BackgroundIn Zimbabwe, 16% of pregnant women aged 15–49 years are infected with HIV. More than 90% of HIV infection in children is through mother-to-child transmission (MTCT). We investigated the effectiveness of the Option B+ in reducing HIV infection and factors associated with HIV transmission among infants born to mothers enrolled in the prevention of mother-to-child transmission (PMTCT) programme.MethodsWe randomly selected 1204 early infant HIV diagnosis test results for HIV-exposed infants and linked these results to maternal clinical records at primary healthcare clinics in Harare to estimate the prevalence of MTCT and to determine the clinical factors associated with MTCT of HIV at 6 weeks.ResultsOf the 1204 infants in the study, 2.5% (95% confidence interval [CI], 1.7–3.5) were infected with HIV at 6 weeks post-delivery. Antiretroviral adherence reduced the odds of HIV infection by about 99% (odds ratio [OR] 0.01 [95% CI, 0.00–0.06]). Both mixed feeding (OR 3.89 [95% CI, 0.92–16.50]) and late initiation of antiretroviral treatment (ART) (after delivery) (OR 3.18 [95% CI, 0.42–23.94]) increased the odds of HIV infection.ConclusionEarly initiation of combination ART reduces 6-week MTCT of HIV in PMTCT programmes to levels similar to those found in controlled trial settings. Exclusive breastfeeding remains important even in the presence of ART.

Perceived Patients’ Satisfaction, Barriers and Implications on Engagement in Antiretroviral Treatment Services in Cameroon within the HIV Test and Treat Context

Introduction: Patients’ satisfaction has been associated with improved adherence, retention and antiretroviral treatment (ART) outcomes. Sustained engagement in ART is a prerequisite for attaining universal ART coverage. This study describes perceived patients’ satisfaction, barriers and implications on engagement in ART services within the context of the HIV Test &Treat (HIV T&T) strategy. Materials and methods: Between August and September 2018, HIV positive clients who initiated ART and key HIV care providers (HCPs) in three HIV clinics in Cameroon were interviewed. Ethical and administrative clearances for the study were obtained from the appropriate quarters. A thematic approach was used to analyze the data. Results: A total of 45 HIV positive clients and 21 HCPs were interviewed. Patients’ satisfaction varied with HIV service. Patient-reported barriers included: long waiting time, poor reception, delay between time of HIV diagnosis and ART initiation, poor coordination between HIV testing and ART services, poor flexibility in ART delivery system, large tablet size of ARVs/indefinite treatment duration, side effects. Inadequate counselling, overcrowding in the HIV clinics, patients’ non-appreciation of ART benefits were reported by patients and HCPs. Some barriers were linked to the HIV T&T strategy and many of them limited patients’ engagement in ART. Conclusion: Patient satisfaction varied with HIV service. Some of the barriers to patients’ satisfaction were linked with the implementation of the HIV T&T strategy and negatively impacted patients’ engagement in ART services. These views should be considered in evaluating and improving the quality of HIV care.

Timeliness of Human Immunodeficiency Virus Diagnosis and Antiretroviral Treatment Initiation in the Era of Universal Testing and Treatment.

We describe the timing of human immunodeficiency virus (HIV) diagnosis and antiretroviral treatment (ART) initiation after implementation of universal testing and treatment policies in New York City (NYC). Using NYC population-based HIV registry data for persons with HIV diagnosed from 2012 through 2015 and followed up through June 2017, we examined trends in the proportion with diagnosis soon after HIV infection (ie, with CD4 cell count ≥500/μL or with acute HIV infection) and used Kaplan-Meier plots and proportional hazards regression to examine the timing of ART initiation after diagnosis. Among 9987 NYC residents with HIV diagnosed from 2012 to 2015, diagnosis was early in 35%, and 87% started ART by June 2017. The annual proportion of persons with early diagnosis did not increase appreciably (35% in 2012 vs 37% in 2015; P = .08). By 6 months after diagnosis, 62%, 67%, 72% and 77% of persons with HIV diagnosed in 2012, 2013, 2014, or 2015, respectively, had started ART, with median (interquartile range) times to ART initiation of 3.34 (1.34-12.75), 2.62 (1.28-10.13), 2.16 (1.15-7.11), and 2.03 (1.11-5.61) months, respectively. Although recommendations for ART initiation on diagnosis are increasingly being implemented, the findings of the current study suggest that immediate treatment initiation is not universal. Continued efforts are needed to expand and better target HIV testing to promote earlier diagnosis.

Bootstrap inference when using multiple imputation.

Many modern estimators require bootstrapping to calculate confidence intervals because either no analytic standard error is available or the distribution of the parameter of interest is nonsymmetric. It remains however unclear how to obtain valid bootstrap inference when dealing with multiple imputation to address missing data. We present 4 methods that are intuitively appealing, easy to implement, and combine bootstrap estimation with multiple imputation. We show that 3 of the 4 approaches yield valid inference, but that the performance of the methods varies with respect to the number of imputed data sets and the extent of missingness. Simulation studies reveal the behavior of our approaches in finite samples. A topical analysis from HIV treatment research, which determines the optimal timing of antiretroviral treatment initiation in young children, demonstrates the practical implications of the 4 methods in a sophisticated and realistic setting. This analysis suffers from missing data and uses the g-formula for inference, a method for which no standard errors are available.

Performance of the Antiretroviral Treatment Program in Ethiopia, 2005-2015: strengths and weaknesses toward ending AIDS

BackgroundEthiopia is one of the countries which has scaled up antiretroviral treatment (ART) over the past decade. This study reviews the performance of the ART program in Ethiopia during the past decade, and identifies successes and weaknesses toward ending AIDS in the country. MethodsA review and synthesis of data was conducted using multiple data sources: reports from all health facilities in Ethiopia to the Federal Ministry of Health, HIV/AIDS estimates and projections, and retrospective cohort and cross-sectional studies conducted between 2005/6 and 2014/15. FindingsThe ART program has been successful over several critical areas: (1) ART coverage improved from 4% to 54%; (2) the median CD4 count/mm3 at the time of ART initiation increased from 125 in 2005/6 to 231 in 2012/13; (3) retention in care after 12 months on ART has increased from 82% to 92%. In spite of these successes, important challenges also remain: (1) ART coverage is not equitable: among regions (5.6%-93%), between children (25%) and adults (60%), and between female (54%) and male patients (69%); (2) retention in care is variable among regions (83%-94%); and, (3) the shift to second-line ART is slow and low (0·58%). InterpretationThe findings suggest that the ART program should sustain the successes and reflect on the shortcomings toward the goal of ending AIDS. It is important to capitalize on and calibrate the interventions and approaches utilized to scale up ART in the past. Analysis of the treatment cascade, in order to pinpoint the gaps and identify appropriate solutions, is commendable in this regard.