Early ART Initiation Research Articles

Timing of HIV testing among pregnant and breastfeeding women and risk of mother-to-child HIV transmission in Malawi: a sampling-based cohort study.

IntroductionPregnant women living with HIV can achieve viral suppression and prevent HIV mother‐to‐child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy, or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi’s PMTCT programme.MethodsWe conducted a two‐stage cohort study among mother–infant pairs in 30 randomly selected high‐volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log‐binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting.ResultsOf 822 mother–infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living <1 hour travel time to the nearest health facility. The risk of unsuppressed VL did not differ between women who had their last positive HIV test during breastfeeding versus pregnancy (adjusted RR [aRR] = 0.87; 95% CI: 0.48 to 1.57). MTCT risk was higher among women who had their last positive HIV test during breastfeeding compared to women who had it during pregnancy (aRR = 6.57; 95% CI: 3.37 to 12.81).ConclusionsMTCT in Malawi occurred disproportionately among women with a last positive HIV test during breastfeeding. Testing delayed until the postpartum period may lead to higher MTCT. To optimize maternal and child health outcomes, PMTCT programmes should focus on early ART initiation and providing targeted testing, prevention, treatment and support to breastfeeding women.

Ocular Manifestations in Patients of HIV(Human Immunodeficiency Virus) Infection on Combined Anti-Retroviral Therapy (CART)

ABSTRACT Aim To determine the prevalence and spectrum of ocular manifestations in PLHIV (people living with Human Immunodeficiency Virus) on cART (combined Antiretroviral Therapy) and correlate them with WHO clinical staging, CD4 count, duration & type of cART. Methods Observational cross-sectional study. Ophthalmic evaluation of 350 PLHIV on cART (at least 6 months) was done. Logistic regression was done to correlate ocular findings with different variables. Results: Prevalence of ocular, anterior & posterior segment manifestations was 15.71%, 10.86%, and 4.00%, respectively. Dry eye(8.00%) being the most common finding. PLHIV with CD4 count ≤350 (OR = 3.1,p < 0.001), in WHO stage 3 (OR = 26.9,p = 0.004) & 4(OR = 60.7,p < 0.001) & on 3rdlineART were at much higher risk of ocular manifestations as compared to those on 2nd (OR = 2.83) and 1stline (OR = 6.6) of therapy. Duration of treatment had a protective (p = 0.01) effect on bilateral manifestations. Conclusion With early initiation of ART, there is significant reduction in the overall prevalence of ocular findings, in the number of opportunistic ophthalmic infections and blinding disorders. Of all the reported ocular findings, anterior segment disorder emerged more often.

Adherence to Antiretroviral Treatment for Prevention of Mother-to-Child Transmission of HIV in Eastern Ethiopia: A Cross-Sectional Study.

IntroductionEven though PMTCT (prevention of mother-to-child transmission) is the most effective option to prevent vertical transmission of HIV, achieving optimal adherence has been a universal challenge to PMTCT, including Ethiopia.ObjectiveTo assess levels of adherence and associated factors among pregnant and lactating mothers on PMTCT at public health facilities in Harar town, Harari region, Eastern Ethiopia.MethodsA facility-based cross-sectional study was conducted from April 01 to April 30, 2019, at the selected public health facilities of Harar town, Harari regional state, Eastern Ethiopia. Adherence was measured using a multi-method tool that includes pill counting and self-reporting method. Binary logistic regression analysis was used to determine factors associated with PMTCT adherence. The results were adjusted for possible confounding variables and P-value <0.05 or CI not including 1 was considered statistically significant.ResultsOf the 190 included patients, 83.2% of them had good adherence to PMTCT. Forgetfulness (79%) and being busy (71%) were among the main reasons for non-adherence to PMTCT. In multivariate logistic regression, participants who have received counseling on side effects were 3.4 times more likely to have good adherence [AOR=3.4, 95% CI: 2.1–9.2]; those with previously known HIV status were 2.1 times more likely to have good adherence to PMTCT [AOR=2.1, 95% CI: 1.6–7.1] and women who were knowledgeable on PMTCT were 5.2 times more likely to have good adherence [AOR=5.2, 95% CI: 1.6–6.28].ConclusionIn this study, the overall level of adherence to PMTCT care and support was 83.2%. Counseling on side effects, knowledge about PMTCT, and pregnancy status during initiation of ART were the factors that determine adherence of pregnant and lactating women towards PMTCT service. Thus, it is recommended to raise awareness about PMTCT among all reproductive-age women by stressing the benefit of the early initiation of ART and by providing information on the possible side effect of the drugs.

Effect of Enhanced Adherence Package on Early ART Uptake Among HIV-Positive Pregnant Women in Zambia: An Individual Randomized Controlled Trial.

We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naïve pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91-1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02-1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support.This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.

The effect of antiretroviral therapy guideline change on health outcomes among youth living with HIV in Uganda

ABSTRACT Opportunistic infections (OIs) are the primary cause of HIV-related morbidity and mortality. To reduce the risk, the ART eligibility criteria were revised to start treatment before advanced disease onset. We evaluated the effect of 2014 HIV clinical guideline changes in Uganda on opportunistic infections and survival among Youth Living with HIV (YLWH). This retrospective cohort analysis used administrative data from the District Health Information System (DHIS2) and the national referral hospital, to compare YLWH, 15–24 years old, who started ART pre-guideline (January 2012–June 2014) and post-guideline (July 2014–December 2016). We assessed the effect using multivariable logistic and Cox Proportional Hazards regression models, respectively. Post-guideline youth had 18% and 30% lower adjusted odds of having an OI at 6 (aOR: 0.82, 95%CI: 0.67, 0.99), and 12 months (aOR: 0.70, 95%CI: 0.58, 0.85) after ART initiation, compared to pre-guideline youth. No significant differences were observed in survival probabilities (Z = 2.56, P-value = 0.11) and adjusted hazard ratios (aHR: 1.55, 95%CI: 0.46, 5.28). Early ART initiation reduced the risk of OIs among YLWH. However, given the existence of geographical and clinical variations in the endemicity, morbidity and mortality associated with different OIs, additional research is still needed.

HIV-positive persons who inject drugs experience poor health outcomes and unmet needs for care services

ABSTRACT Comparison of social determinants of health and clinical outcomes between HIV-positive persons who inject drugs (PWID) and HIV-positive persons who do not inject drugs is essential to understanding disparities and informing HIV prevention and care efforts; however, nationally representative estimates are lacking. Interview and medical record data were collected for the Medical Monitoring Project during 2015–2018 among U.S. adults with diagnosed HIV. Among HIV-positive PWID (N=340) and HIV-positive persons who do not inject drugs (N=11,475), we reported weighted percentages and prevalence ratios with predicted marginal means to compare differences between groups (P<.05). Associations with clinical outcomes were adjusted for age, race/ethnicity, and gender. HIV-positive PWID were more likely to be homeless (29.1% vs. 8.1%) and incarcerated (18.3% vs. 4.9%). HIV-positive PWID were less likely to be retained in HIV care (aPR: 0.85 [95% CI: 0.77–0.94]), and were more likely to have poor HIV outcomes, have unmet needs for care services (aPR: 1.50 [1.39–1.61]), seek non-routine care, and experience healthcare discrimination (aPR: 1.42 [1.17–1.73]). Strengthening interventions supporting (1) continuity of care given high levels of incarceration and housing instability, (2) early ART initiation and adherence support, and (3) drug treatment and harm reduction programs to limit transmission risk may improve outcomes among HIV-positive PWID.

Identifying and predicting longitudinal trajectories of care for people newly diagnosed with HIV in South Africa.

BackgroundPredicting long-term care trajectories at the time of HIV diagnosis may allow targeted interventions. Our objective was to uncover distinct CD4-based trajectories and determine baseline demographic, clinical, and contextual factors associated with trajectory membership.MethodsWe used data from the Sizanani trial (NCT01188941), in which adults were enrolled prior to HIV testing in Durban, South Africa from August 2010–January 2013. We ascertained CD4 counts from the National Health Laboratory Service over 5y follow-up. We used group-based statistical modeling to identify groups with similar CD4 count trajectories and Bayesian information criteria to determine distinct CD4 trajectories. We evaluated baseline factors that predict membership in specific trajectories using multinomial logistic regression. We examined calendar year of participant enrollment, age, gender, cohabitation, TB positivity, self-identified barriers to care, and ART initiation within 3 months of diagnosis.Results688 participants had longitudinal data available. Group-based trajectory modeling identified four distinct trajectories: one with consistently low CD4 counts (21%), one with low CD4 counts that increased over time (22%), one with moderate CD4 counts that remained stable (41%), and one with high CD4 counts that increased over time (16%). Those with higher CD4 counts at diagnosis were younger, less likely to have TB, and less likely to identify barriers to care. Those in the least favorable trajectory (consistently low CD4 count) were least likely to start ART within 3 months.ConclusionsOne-fifth of people newly-diagnosed with HIV presented with low CD4 counts that failed to rise over time. Less than 40% were in a trajectory characterized by increasing CD4 counts. Patients in more favorable trajectories were younger, less likely to have TB, and less likely to report barriers to healthcare. Better understanding barriers to early care engagement and ART initiation will be necessary to improve long-term clinical outcomes.

Prevalence and Predictors of Virological Failure Among Adults Living with HIV in South Wollo Zone, Northeast Ethiopia: A Retrospective Cohort Study.

BackgroundHighly active antiretroviral therapy has dramatically altered progression of HIV infection and significantly improved patients’ quality of life. However, drug resistance with consequent treatment failure raises the need for much more expensive and toxic second-line regimens. Thus, this study aimed at investigating the predictors of virologic failure among adults in Northeast Ethiopia.MethodsA retrospective cohort study was carried out among adults who started first-line antiretroviral treatment from September 2005 to January 2018. Data were collected from patients’ medical records, entered and validated using EpiData version 3.1 and then exported to SPSS version 20 for analysis. Binary logistic regression was carried out; odds ratio with 95% CI was used to identify covariates associated with virologic failure. Statistical significance was considered at p-value <0.05.ResultsA total of 384 patients with mean age of 35.73±9.44 years were consecutively enrolled; of which, 213 (55.5%) were females, 255 (66.4%) had WHO clinical stage III/IV, and 130 (33.9%) had baseline CD4 count <100 cells/mm3. Mean baseline CD4 count was 179 cells/mm3 (range: 2–853 cells), and 158 (41.1%) participants were on AZT/3TC/NVP. Virological failure was diagnosed among 61 (15.9%) patients. The mean time to virologic failure after initiation of ART was 63.80 months (range: 17–150 months). After adjusting for other confounders, risk of experiencing virologic failure was significantly associated with being divorced (AOR 3.40, 95% CI 1.20–9.59), being naïve to ART (AOR 2.55, 95% CI 1.23–5.28), low (<100) baseline CD4 count (AOR 2.39, 95% CI 1.03–5.54) and nonadherence (AOR 6.73, 95% CI 3.29–13.76).ConclusionIn this study, the prevalence of antiretroviral treatment failure was 15.9%. Being divorced, being naïve to antiretroviral therapy, low (<100 cells/mm3) baseline CD4 count and nonadherence were found to be significant predictors of virologic failure. ART programs should focus on early HIV diagnosis and ART initiation as well as enhanced adherence support.

Magnitude of Opportunistic Infections and Associated Factors Among HIV-Positive Adults on ART at Selected Public Hospitals in Sidama National Regional State, Southern Ethiopia.

BackgroundOpportunistic infections are late complications of HIV infection due to the depletion of the immune system. It is a major public health problem and high morbidity AIDS patients die of AIDS-related infections in developing countries like Ethiopia. Identification of opportunistic infections (OIs) is important to develop a specific intervention. Therefore, the aim of this study was to assess the burden and associated factors of opportunistic infections.MethodsA facility-based cross-sectional study was conducted on 420 randomly selected HIV/AIDS patients taking anti-retroviral therapy. Data were collected from selected hospitals in Sidama Regional State based on population proportion to size. Data were collected by a pre-tested questionnaire and a pre-tested checklist from the medical records of patients. Data were entered and analyzed for descriptive and logistic regression models by SPSS v.23. The result declared as statistically significant at p < 0.05.ResultsThe magnitude of opportunistic infections was 39.6%. Major identified OIs were oral candidiasis 23.2%, recurrent bacterial pneumonia 21.5%, herpes zoster 6.3%, and pulmonary tuberculosis 6.0%. The magnitude of opportunistic associated with older age [AOR=3.50, 95% CI:1.85, 6.61], no formal education [AOR=4.54, 95% CI:1.81, 11.37], initial CD4 count less than 200 cells/mm3 [AOR=3.10, 95% CI:1.61, 5.96], who interrupt ART medicines [AOR=3.21, 95% CI:1.86, 5.56] and khat chewing [AOR=4.24, 95% CI:2.07, 8.68] when compared to their counterparts.ConclusionThe overall magnitude of opportunistic infections was high when compared with other studies. Health officials and clinicians need to give attention to the strengthening of the provision if ART with prophylaxis on early stage and adherence, implementation of the TB/HIV collaboration activity, and early initiation of ART to reduce opportunistic infections.

Effectiveness of Maternal Transmission Risk Stratification in Identification of Infants for HIV Birth Testing: Lessons From Zimbabwe.

Background:In 2017, Zimbabwe adopted a modified version of the World Health Organization 2016 recommendation on HIV birth testing by offering HIV testing at birth only to infants at “high risk” of HIV transmission. There is limited evidence on the effectiveness of this approach. Our study assessed the sensitivity and specificity of birth testing “high risk” infants only.Methods:We conducted a cross-sectional study at 10 health facilities from November 2018 to July 2019. A nucleic acid test for HIV was performed on all HIV-exposed infants identified within 48 hours of life, irrespective of risk status. Univariate and bivariate analyses were used to estimate the performance of the risk screening tool.Results:HIV nucleic acid test was successfully performed on 1970 infants (95%), of whom 266 (13.5%) were classified as high-risk infants. HIV prevalence for all infants tested was 1.5% (95% CI: 1% to 2%), whereas prevalence among high-risk infants and low-risk infants was 6.8% (95% CI: 3.7% to 9.8%) and 0.6% (95% CI: 0.3% to 1%) respectively. Sensitivity and specificity of the maternal risk screening tool was at 62.1% (95% CI: 44.4% to 79.7%) and 87.2% (95% CI: 85.7% to 88.7%), respectively; positive and negative predictive values were 6.8% (95% CI: 3.7% to 9.8%) and 99.4% (95% CI: 99.0% to 99.7%) respectively.Conclusions:Despite high negative predictive value, sensitivity was relatively low, with potential of missing 2 in every 5 HIV infected infants. Given the potential benefits of early ART initiation for all exposed infants, where feasible, universal testing for HIV-exposed infants at birth may be preferred to reduce missing infected infants.

Tuberculosis and its association with CD4+ T cell count among adult HIV positive patients in Ethiopian settings: a systematic review and meta-analysis

BackgroundTuberculosis (TB) and HV have been intertwined and makeup a deadly human syndemic worldwide, especially in developing countries like Ethiopia. Previous studies have reported different TB incidences and its association with CD4+ T cell counts among HIV positive patients in Ethiopia. Thus, the goal of this meta-analysis was, first, to determine pooled incident TB among adult HIV positive patients, and second, to assess the association between incident TB and baseline CD4+ T cell count strata’s.MethodsWe searched PubMed, Cochrane library, Science Direct and Google scholar databases from June 1 to 30, 2018. The I2 statistics and Egger’s regression test was used to determine heterogeneity and publication bias among included studies respectively. A random effects model was used to estimate pooled incident TB and odds ratio with the respective 95% confidence intervals using Stata version 11.0 statistical software.ResultsA total of 403 research articles were identified, and 10 studies were included in the meta-analysis. The pooled incident TB among adult HIV infected patients in Ethiopia was 16.58% (95% CI; 13.25–19.91%). Specifically, TB incidence in Pre-ART and ART was 17.16% (95% CI; 7.95–26.37%) and 16.24% (95% CI; 12.63–19.84%) respectively. Moreover, incident TB among ART receiving patients with baseline CD4+ T cell count < and > 200 cells/mm3 was 28.86% (95% CI; 18.73–38.98%) and 13.7% (95% CI; 1.41–25.98%) correspondingly. The odds of getting incident TB was 2.88 (95% CI; 1.55–5.35%) for patients with baseline CD4+ T cell count < 200 cells/mm3 compared to patients with baseline CD4+ T cell count > 200 cells/mm3.ConclusionHigh incident TB among adult HIV positive patients was estimated, especially in patients with CD4+ T cell count < 200 cells/mm3. Therefore, Early HIV screening and ART initiation, as well as strict compliance with ART and increasing the coverage of TB preventive therapy to more risky groups are important to prevent the problem.Trial registrationStudy protocol registration: CRD42018090802.

Predictors of Early ART Initiation Among HIV + Infants in Kenya: A Retrospective Review of HITSystem Data from 2013 to 2017.

Early initiation of antiretroviral therapy (ART, before 12weeks of age) among infants living with HIV reduces infant mortality and slows disease progression. However, inefficiencies in early infant diagnosis processes prevents timely ART initiation among infants living with HIV in Kenya. This study assesses predictors of early ART initiation among infants living with HIV in Kenya. We retrospectively reviewed data from 96 infants living with HIV born between January 2013 and June 2017 at 6 Kenyan government hospitals. The primary outcome was infant receipt of ART by 12weeks of age. We assessed bivariable and multivariable predictors of ART initiation by 12weeks of age. Among 96 infants living with HIV, 82 (85.4%) infants initiated ART at a median infant age of 17.1weeks. Of the 82 infants who started ART, only 17 (20.7%) initiated ART by 12weeks of age. In multivariable logistic regression analyses, testing per national guidelines (< 7weeks of age) (aOR 40.14 [3.96-406.97], p = 0.002), shorter turnaround time for result notification (≤ 4weeks) (aOR 11.30 [2.02-63.34], p = 0.006), and ART initiation within 3days of mother notification (aOR 7.32 [1.41-38.03], p = 0.006) were significantly associated with ART initiation by 12weeks of age. Current implementation of early infant diagnosis services in Kenyan only achieves targets for early ART initiation in one-fifth of infants with HIV. Strengthening services to support earlier infant testing and streamlined processes for early infant diagnosis may increase the proportion of infants who receive timely ART.

High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy

Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.

OP 2.6 - Utilising correlative PET/CT and multiscale imaging to define the dynamics of SIV-infected cells from early ART initiation to the rebound after analytic treatment interruption

OP 2.6 - Utilising correlative PET/CT and multiscale imaging to define the dynamics of SIV-infected cells from early ART initiation to the rebound after analytic treatment interruption

The effect of HIV infection and exposure on cognitive development in the first two years of life in Malawi

To assess longitudinal patterns and determinants of cognitive development in infants living with HIV, infants exposed to maternal HIV infection, and HIV-unexposed infants. Prospective, community-based cohort study of 555 Malawian infants aged 8 weeks to 24 months, using multivariable linear mixed-effects regression models with random intercepts to analyze repeated measures of cognitive function. At 3 months of age, cognitive scores on the Bayley Scales of Infant Development (BSID 3rd edition) were lower in the 96 HIV-infected infants (mean=14.1 (SD:4.8)) compared to the 289 HIV-exposed (mean=16.5 (SD:3.7)) and the 170 unexposed infants (mean=17.5 (SD:3.3)). Over the first two years of life, the small deficit in cognitive development of infants living with HIV who survived and remained in care did not increase (mean score 52.9 among HIV-infected vs 55.6 among HIV unexposed). In multivariable analysis, malnutrition and a more advanced clinical infant HIV stage had a negative impact on cognition at age 3, while financial security, care by the biological mother, and ART for mother and child were associated with better cognitive status at this young age. The positive influence of maternal ART reversed with age. Malawian infants exposed to HIV had a cognitive development that was similar to their unexposed peers in the first two years of life, while that of HIV infected infants lagged behind from the start. Early initiation of effective ART in all HIV infected mothers and infants, and prevention of infant malnutrition are important to safeguard cognitive development of children affected by HIV.

887. High Rates of Virologic Suppression Achieved in HIV-1–Infected Adults Rapidly Starting Antiretroviral Therapy (ART) with the Single-Tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) 800/150/200/10 mg Regardless of Baseline Disease Characteristics: Week 48 Subgroup Analyses From the Phase 3 DIAMOND Trial

BackgroundRapid initiation of ART requires that clinicians start therapy prior to having baseline laboratory Results. High rates of virologic suppression and retention were reported in the DIAMOND trial. Efficacy and safety are presented, according to baseline disease characteristics.MethodsDIAMOND (ClinicalTrials.gov: NCT03227861), a phase 3, single-arm, open-label, prospective, multicenter study, assessed efficacy/safety of D/C/F/TAF in rapid initiation. Adults enrolled within 14 days of diagnosis and started D/C/F/TAF without baseline laboratory results; investigators reviewed results as they became available. Primary endpoint was virologic suppression (HIV-1 RNA < 50 copies[c]/mL; intent-to-treat (ITT); Food and Drug Administration [FDA] snapshot) at Week 48. Virologic suppression <50 c/mL and <200 c/mL were also assessed via an observed analysis, excluding patients with missing data.ResultsOverall, 109 patients were enrolled; 25% had HIV-1 RNA ≥100,000 c/mL and 21% had CD4+ < 200 cells/μL (Table 1). 21% of patients started therapy within 24 hours of diagnosis. At Week 48, 84%, and 88% of patients had HIV-1 RNA <50 c/mL and <200 c/mL (FDA snapshot), respectively. In the observed analysis, 96% and 100% of patients had HIV-1 RNA <50 c/mL and <200 c/mL, respectively, at Week 48. Earlier ART initiation, HIV-1 RNA <100,000 c/mL, and CD4+ >200 cells/μLwere associated with numerically higher virologic suppression rates (ITT-FDA snapshot; Table 2). No patient discontinued due to lack of efficacy or met protocol-defined virologic failure (PDVF) criteria. In the observed analysis, virologic suppression rates were consistent across all subgroups; all patients were suppressed <200 c/mL at Week 48. One patient discontinued due to an adverse event (AE); incidences of grade 3/4 (10%) and serious (9%) AEs were low, with no serious AEs related to study drug and no deaths.ConclusionIn the first phase 3 study of an STR in a rapid initiation model, no patients rapidly starting D/C/F/TAF discontinued therapy due to lack of efficacy or had PDVF through 48 weeks. High rates of virologic suppression were achieved and maintained with a variety of baseline characteristics, and treatment was safe and well tolerated, indicating D/C/F/TAF as a preferred ART option for patients rapidly starting treatment. Disclosures All Authors: No reported Disclosures.

Prevalence And Predictors Of Opportunistic Infections Among HIV Positive Adults On Antiretroviral Therapy (On-ART) Versus Pre-ART In Addis Ababa, Ethiopia: A Comparative Cross-Sectional Study.

PurposeData comparing the burden of the opportunistic infections among the Pre-ART and On-ART HIV-infected patients in Ethiopia are scarce. Therefore, this study aimed to compare the prevalence and predictors of opportunistic infections in Pre-ART and On-ART HIV-infected patients.MethodsA comparative cross-sectional study was conducted among adult patients infected with HIV and who were on Pre-ART or On-ART and followed up from 2012 to 2016 in Zewditu Memorial Hospital, Addis Ababa. Those patients who were infected with HIV, but not eligible for ART were categorized under Pre-ART follow-up (n=192) and those patients who started taking ART were categorized under the On-ART follow-up group (n=192). Patients were included in the study by using simple random sampling technique from the list of the patients registered in the ART follow-up database. The presence of opportunistic infections along with clinical findings and baseline laboratory data was extracted from the ART follow-up database and the medical records of the patients using a standardized checklist. Factors associated with the development of opportunistic infections were analyzed using multi-variable binary logistic regression analysis.ResultsThe overall prevalence of opportunistic infections was found to be 33.6% (95% CI; 28.9–38.5). The prevalence of opportunistic infections among the Pre-ART group (38%) was higher than On-ART group (29.2%) (P-value = 0.04). Pulmonary tuberculosis was the most common opportunistic infection observed in both Pre-ART and On-ART groups. Being in the WHO clinical Stage III (AOR = 2.1; 95% CI 1.1–3.9) or Stage IV (AOR = 3.6; 95% CI 1.7–7.7) were independent predictors for the development of opportunistic infections.ConclusionThe prevalence of opportunistic infections among the HIV-infected patients who were in Pre-ART was higher than On-ART group. This finding reinforces the need for early initiation of ART for HIV-infected patients irrespective of their CD4 counts.

Myeloid Derived Suppressor Cells Expansion Persists After Early ART and May Affect CD4 T Cell Recovery

Myeloid-derived suppressor cells (MDSC) are expanded during HIV-1 infection and correlated with disease progression. MDSC expand in the early phase of primary infection depending on TRAIL level. In this study we evaluated the effect of ART on the frequency of MDSC in patients with primary HIV infection (PHI), and their impact on CD4 T cell reconstitution. MDSC frequency was evaluated by flow-cytometry in 60 PHI patients at 12, 24 and 48 weeks after ART initiation. Cytokine plasma levels were evaluated by Luminex technology at the same time points. The capacity of MDSC to modulate hematopoietic early progenitor cells' expansion was evaluated using the OP9/Dl1 in vitro system. As previously described, polymorphonuclear-MDSC (PMN-MDSC) frequency was higher in PHI compared to healthy donors. Interestingly, 48 weeks of successful ART failed to normalize the PMN-MDSC frequency. Moreover, PMN-MDSC frequency was not correlated with residual viral load, suggesting that the persistence of PMN-MDSC was not due to residual viral replication. Interestingly, patients with low PMN-MDSC frequency (<6%) at T0 had a higher HIV DNA at the same time point than individuals with high PMN-MDSC frequency (>6%). We also found an inverse correlation between PMN-MDSC frequency and CD4-T cell count at 48 weeks post-ART, which was confirmed by multivariate analysis adjusting for age and CD4 T cell number at baseline. These data suggest that the persistence of PMN-MDSC may impact CD4 T cell recovery. Indeed, in vitro PMN-MDSC impaired the expansion of CD34+CD38- hematopoietic early progenitors. Further, a balance between TRAIL and GM-CSF may be necessary to maintain a low MDSC level. In conclusion, early ART initiation was not able to normalize PMN-MDSC frequency that might impact the CD4 T cell recovery. These data open new questions regarding the clinical impact of MDSC persistence in HIV+ patients, in particular on non-AIDS related diseases.

8 - Persistent elevation of Tim-3 and PD-1 on memory T cells despite early ART initiation during primary HIV infection

8 - Persistent elevation of Tim-3 and PD-1 on memory T cells despite early ART initiation during primary HIV infection

Cost-effectiveness and budget impact of immediate antiretroviral therapy initiation for treatment of HIV infection in Côte d'Ivoire: A model-based analysis.

IntroductionThe Temprano and START trials provided evidence to support early ART initiation recommendations. We projected long-term clinical and economic outcomes of immediate ART initiation in Côte d’Ivoire.MethodsWe used a mathematical model to compare three potential ART initiation criteria: 1) CD4 <350/μL (ART<350/μL); 2) CD4 <500/μL (ART<500/μL); and 3) ART at presentation (Immediate ART). Outcomes from the model included life expectancy, 10-year medical resource use, incremental cost-effectiveness ratios (ICERs) in $/year of life saved (YLS), and 5-year budget impact. We simulated people with HIV (PWH) in care (mean CD4: 259/μL, SD 198/μL) and transmitted cases. Key input parameters to the analysis included first-line ART efficacy (80% suppression at 6 months) and ART cost ($90/person-year). We assessed cost-effectiveness relative to Côte d’Ivoire’s 2017 per capita annual gross domestic product ($1,600).ResultsImmediate ART increased life expectancy by 0.34 years compared to ART<350/μL and 0.17 years compared to ART<500/μL. Immediate ART resulted in 4,500 fewer 10-year transmissions per 170,000 PWH compared to ART<350/μL. In cost-effectiveness analysis, Immediate ART had a 10-year ICER of $680/YLS compared to ART<350/μL, ranging from cost-saving to an ICER of $1,440/YLS as transmission rates varied. ART<500/μL was “dominated” (an inefficient use of resources), compared with Immediate ART. Immediate ART increased the 5-year HIV care budget from $801.9M to $812.6M compared to ART<350/μL.ConclusionsIn Côte d’Ivoire, immediate compared to later ART initiation will increase life expectancy, decrease HIV transmission, and be cost-effective over the long-term, with modest budget impact. Immediate ART initiation is an appropriate, high-value standard of care in Côte d’Ivoire and similar settings.