Antiretroviral Therapy Initiation Research Articles

Assessing BE FASTER, a Community of Practice Among Ryan White Part A Clinics in Houston, to Increase Rapid Initiation of Antiretroviral Therapy: A Qualitative, Longitudinal Study.

Rapid initiation of antiretroviral therapy (Rapid ART) is a key strategy for the Ending the HIV Epidemic inititative. In Harris County, Texas, a priority Ending the HIV Epidemic jurisdiction, 57% of persons with HIV receive care at 1 of 5 public agencies that receive funding from the Ryan White HIV/AIDS Program. The Ryan White HIV/AIDS Program is administered by the US Department of Health and Human Services, Health Resources and Services Administration, and HIV/AIDS Bureau. This program administers grants to clinics and local/state programs to deliver medical and support services (Part A) for low-income persons with HIV. In 2019, 39% of recently diagnosed persons with HIV in Houston took > 1 month to start ART. Herein, the authors evaluate the acceptability of the Baylor College of Medicine ECHO Facilitating Antiretroviral StART Earlier (BE FASTER) program, a community of practice collaborative among 5 Ryan White Part A Clinics, to increase Rapid ART in Harris County, Texas. Semistructured interviews across 4 time points were conducted among health care workers participating in the BE FASTER program. Interviews took place from November 2021 through February 2023 and were analyzed using rapid qualitative analysis. A total of 29 participants were interviewed. Analyses revealed 6 themes: 1) Rapid ART protocols varied between clinics; 2) participants were interested in getting to know Rapid ART staff at other Ryan White clinics; 3) participants enjoyed the active components of BE FASTER and asked for more opportunities to engage; 4) at the end of BE FASTER, participants reported that they had streamlined their processes for Rapid ART, but barriers to long-term retention remained an ongoing challenge; 5) participants reported an increased sense of community from participating in the BE FASTER program; and 6) overall, participants had a positive experience with BE FASTER. Participants found BE FASTER valuable and reported a positive impact on their cross-agency interactions. The BE FASTER program using the ECHO model can augment the creation of cross-organizational networks for Rapid ART.

Time to initiation of antiretroviral therapy and its predictors among newly diagnosed HIV positive at the selected public health centers in Adama Town, Ethiopia

IntroductionAntiretroviral therapy (ART) has significantly reduced HIV infections, but late initiation remains a major issue. This study aimed to identify predictors of ART initiation among newly diagnosed HIV-positive patients in Adama town.MethodA retrospective cohort study was conducted, with 396 newly diagnosed HIV-positive patients. This study used a survival analysis approach, including Kaplan-Meier plots, the log-rank test, and the Cox proportional hazards model.ResultThe incidence rate was 152 per 1000 person-days for early initiation after HIV positive confirmed. In the adjusted model, gender, VCT test, disclosure status, having children in the home, opportunistic infections, and HIV/TB co-infections were significantly associated with time to ART initiation.ConclusionTo enhance early ART initiation, healthcare programs should prioritize support for women patients, promote HIV serostatus disclosure, and improve access to VCT testing. Targeted interventions for those with comorbidities and support for families with children are also essential.

Acute retroviral syndrome.

To review the most important recent literature on the definition, epidemiology, clinical presentation, pathogenesis and treatment of the acute retroviral syndrome (ARS), a constellation of nonspecific symptoms and transient illness occuring in at least 50% of persons shortly after HIV acquisition. ARS is driven by initial rapid HIV viral replication and dissemination after acquisition, followed by immune activation and massive systemic inflammation. A more detailed understanding of ARS is important for the implementation of early detection efforts, treatment and public health strategies to control HIV. Recent research has provided deeper insights into ARS. Key findings include associations of ARS with heightened immune activation and elevated levels of IFNγ and multiple other cytokines, particularly IP-10, as well as with higher viral load and more severe CD4+ depletion during acute infection. These negative impacts can be mitigated by early antiretroviral therapy initiation and long-term outcomes are generally similar in treated individals with or without ARS. Current findings underscore the importance of early detection and intervention in ARS to mitigate long-term health impacts and inform the development of targeted therapeutic strategies.

Assessment of Virologic Suppression and Retention in Care 6 Years After Rapid Initiation of Antiretroviral Therapy.

In a single-center retrospective follow-up study, no difference in retention in care or virologic suppression was noted between rapid and delayed initiation of antiretroviral therapy at 6-year follow up in participants who were antiretroviral naive. Further study is needed to assess the long-term impact of rapidly starting antiretroviral therapy.

HIV associated motor neuron disease (MND): A case series with systematic review of literature.

Human immunodeficiency virus (HIV) associated motor neuron disease (MND) is very rare. HIV infection can cause an MND-like syndrome due to central nervous system (CNS) involvement de novo or during antiretroviral therapy (ART) due to CNS escape. We present two cases: one with a classic amyotrophic lateral sclerosis (ALS) phenotype, which was the manifestation of symptomatic CNS escape from ART, and the second with a primary lateral sclerosis (PLS) phenotype associated with underlying HIV infection. A systematic review of published literature of people living with HIV (PLHIV) who developed ALS/ MND was conducted using the PubMed, Embase, and Lilacs databases. A total of 91 cases were found, 89 of which were obtained from 37 articles, and two were included from our own case series. In patients with HIV-associated MND, 63 patients reviewed had a classic ALS phenotype followed by progressive muscular atrophy variant (12), progressive bulbar palsy (8), PLS (7) and bulbar onset ALS (1). Neuroimaging, electrophysiology, cerebrospinal fluid (CSF) analysis, CSF and serum HIV viral load, and CD4 count investigations were used for diagnosis. Following the initiation or modification of antiretroviral therapy (ART), approximately 70% exhibited an improvement or a stable disease course. HIV-associated MND is a rare condition that can occur in both ART-naive individuals and those on treatment. A proportion of cases (~ 70%) show improvement with ART. Accurate diagnosis requires the exclusion of opportunistic infections, which remains a critical yet challenging aspect of managing this condition.

Autovaccination revisited: potential to boost antiviral immunity and facilitate HIV-1 cure/remission in children.

To review the concept of autovaccination as a strategy to boost anti-HIV-1 immunity and improve immune control, especially as a means to facilitate cure/remission in paediatric HIV-1 infection, where effective interventions in clinical testing remain limited compared to adults. Early autovaccination studies, conducted 15-25 years ago, suggested potential immunological benefits from exposure to autologous virus in both children and adults, specifically when antiretroviral therapy (ART) was initiated during acute infection. More recent work in nonhuman primates (NHPs) has shown that early ART initiation can significantly reduce the viral setpoint following treatment interruption, primarily through CD8+ T-cell responses, and prevent early immune escape - a phenomenon commonly observed in ART-naive acute infections. Additionally, NHP studies indicate that multiple, short analytical treatment interruptions (ATIs) can delay viral rebound and further lower the viral setpoint via enhanced CD8+ T-cell responses. Recent studies in NHP support the potential for autovaccination via short ATIs to enhance antiviral immunity and improve immune control of HIV-1. With well tolerated, well monitored ATI protocols, autovaccination could be a valuable approach to facilitating cure/remission in children living with HIV (LWH), in whom very early-ART initiation and early-life immunity are associated with low viral reservoirs and high cure/remission potential.

Clinical outcomes among HIV positive babies below 18 months of age, diagnosed under the Early Infant Diagnosis (EID) programme, India: a mixed-methods study.

Clinical outcomes among HIV positive babies below 18 months of age, diagnosed under the Early Infant Diagnosis (EID) programme, India: a mixed-methods study.

Impact of Age of Sexual Debut on HIV Care Engagement Among Sexual and Gender Minorities in Nigeria.

Sexual and gender minorities (SGM) bear a high burden of HIV. The age of anal sexual debut may influence HIV care engagement. Our objective was to evaluate this relationship to help health care providers promote and anticipate future HIV care engagement among at-risk SGM. The TRUST/RV368 study provided HIV testing and treatment at SGM-friendly clinics in Abuja and Lagos, Nigeria. Self-reported age of sexual debut was dichotomized as <16 or ≥16 years. Multivariable logistic models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association of sexual debut with (1) HIV testing history, (2) HIV testing at the clinics, (3) initiation of antiretroviral therapy (ART) within 6 months of a clinic diagnosis, and (4) viral suppression within 12 months of ART initiation. Of the 2680 participants, 30% (n = 805) reported a sexual debut <16 years. Those with an <16-year debut had significantly more receptive sex partners, condomless sex, and transactional sex (all P < 0.01) and were 24% less likely to have tested for HIV before enrollment (aOR: 0.76; CI: 0.62 to 0.93). However, <16-year debut was not associated with HIV testing, receiving ART, or achieving viral suppression once engaged with TRUST/RV368 (all P > 0.05). SGM with <16-year debut engaged in behaviors that could increase HIV risk and were less likely to have a history of HIV testing. However, once enrolled in SGM-friendly clinics, uptake of HIV care was not associated with <16-year debut, suggesting that SGM-friendly care models may promote HIV care engagement.

Shingles in HIV: Outcome and discovery.

Background: Herpes zoster (HZ) is a frequent manifestation in people living with HIV (PLHIV), with a significantly higher incidence compared to the general population. It often presents as an early indicator of immunosuppression, making timely diagnosis and treatment crucial. Methods: This retrospective study, conducted from January 2015 to September 2024, analyzed 45 PLHIV diagnosed with HZ. Patients were recruited from the Infectious Diseases Department (for HIV-related HZ cases) and the Dermatology Department (for complicated HZ cases requiring hospitalization). Clinical and demographic data were collected, including ART status, HZ presentation, and treatment outcomes. Results: The mean patient age was 36.35years, with a male predominance (M/F ratio: 8). Among the cohort, 12 patients had undiagnosed HIV, and HZ was the presenting symptom that led to HIV diagnosis. The thoracic metameric variant was the most common, with erythematous-vesicular, necrotic-hemorrhagic, and bullous forms observed. 21 patients were on antiretroviral therapy (ART), six of whom developed HZ shortly after ART initiation. Treatment involved oral or intravenous acyclovir, with hospitalization required for complicated or multi-metameric forms and high-risk patients. Outpatient management with close monitoring was provided for stable cases. Conclusions: HZ remains a significant opportunistic infection in PLHIV, often serving as a sentinel sign of undiagnosed HIV. Early HIV screening in patients presenting with HZ and timely initiation of antiviral therapy are essential for improved outcomes. Enhanced awareness and integrated HIV-HZ management strategies are crucial in clinical practice.

Effect of antiretroviral therapy on retention of people living with HIV in India (2012-2017): a retrospective, cohort study.

Effect of antiretroviral therapy on retention of people living with HIV in India (2012-2017): a retrospective, cohort study.

Patterns of linear growth among children and adolescents living with HIV on antiretroviral therapy in Zimbabwe and Zambia

BackgroundAdolescents with HIV (AWH) frequently exhibit impaired growth, which manifests as stunting and wasting. We studied trajectories in leg-length (appendicular), sitting (axial), and standing height among AWH on antiretroviral therapy (ART), determining peak height velocity (PHV) and age at PHV (aPHV).MethodsAnalyses used VITALITY trial data from Zimbabwe and Zambia (PACTR20200989766029), which recruited AWH (11-19 years) established on ART to determine whether vitamin D3/calcium supplementation improves bone health. The study enrolled participants between January and December 2021. Weight-for-age and height-for-age z-scores (WAZ/HAZ) were calculated from 12-weekly anthropometry over 96 weeks. Height trajectory analyses used SuperImposition by Translation And Rotation (SITAR) methods adjusting for height, tempo (aPHV) and velocity. Linear associations between vitamin D/calcium supplementation, HIV-specific factors, WAZ, HAZ, and SITAR parameters were determined.ResultsOverall, 842 participants (53·2% female; median age 15·5 [IQR:13·2-17·9] years), were taking ART for median 9·8(IQR:6·3–12·3) years. Mean(SD) HAZ was 1·21(1·05) in females, -1·68(1·05) in males. Overall, 251(29·8%) AWH were stunted (HAZ < -2) and 253(30%) wasted (WAZ < -2). Standing, appendicular and axial aPHVs were: Female 13·4, 13·3, 13·9 years; Males 15·3, 15·0, 15·8 years. Unsuppressed viral-load(VL) and delayed ART initiation (age > 4-years) were associated with later aPHV and shorter axial height in females. In all, unsuppressed VL had a more negative effect on aPHV for axial (Females: β = 0·39 years [95%CI:0·12,0·65]; Males: β = 0·45 [95%CI:0·10,0·80]) than appendicular growth (Females: β = 0.31 [95%CI 0·08,0·53]; Males: β = 0·2 [95%CI:-0·17,0·56]). Conversely, delayed ART initiation was more negatively related to aPHV for appendicular (Females: β = 0·25 [95% CI:0·08,0·43]; Males: β = 0·63 [95%CI:0·32, 0·93] than axial growth (Females: β = 0·13 [95%CI:-0·08,0·34]; Males: β = 0·56 [95%CI:0·28,0·86]. Lower HAZ and WAZ were associated with lower height, later aPHV and lower PHV. At 48-week vitamin-D3/calcium supplementation had no effect on the growth pattern.ConclusionUnsuppressed viral load and delayed ART-initiation predicted later aPHV. Stunting and wasting were associated with attenuated growth velocity and later aPHV. Adolescents with HIV experience persistent linear growth impairments, potentially persisting into adulthood.Trial registration(PACTR20200989766029||http://www.pactr.org/); First registered on 03/09/2020.

Efficacy and Safety of the Two-Drug Regimen Dolutegravir/Lamivudine in Adolescents Living With HIV-1 Naive to Antiretroviral Therapy at 48 Weeks (DANCE): A Single-Arm, Open-label, Phase 3b Trial.

Dolutegravir/Lamivudine is recommended for initial antiretroviral therapy (ART) in adults living with HIV-1; however, no clinical trials have assessed this regimen in adolescents, a potentially more challenging population to treat. We evaluated efficacy, safety, and pharmacokinetics of dolutegravir/lamivudine as initial ART in adolescents living with HIV-1. Nine centers in Thailand, Kenya, and South Africa. In the single-arm, open-label, phase 3b DANCE study (NCT03682848), adolescents naive to ART aged ≥12 to <18 years, weighing ≥25 kg, with plasma HIV-1 RNA 1000 to ≤500,000 copies/mL received single once-daily dolutegravir/lamivudine fixed-dose combination tablet orally for 48 weeks (treatment phase). The primary endpoint was proportion of participants with HIV-1 RNA <50 copies/mL at Week 48 (Snapshot; intention-to-treat-exposed [ITT-E] population). Safety outcomes were evaluated in the safety population. Both the ITT-E and safety populations consisted of participants who received ≥1 dose of dolutegravir/lamivudine (N=32). A sensitivity analysis was performed using data from all but two participants who were withdrawn before Week 48 due to site closure (n=30). At Week 48, 26/32 (81%; 95% CI, 64%-93%) participants had HIV-1 RNA <50 copies/mL; in sensitivity analyses, 26/30 (87%; 95% CI, 69%-96%) achieved virologic suppression. No confirmed virologic withdrawals or deaths were reported. One drug-related adverse event was reported (grade 3 decreased glomerular filtration rate) and was the only adverse event leading to study withdrawal at data cut. Pharmacokinetic parameters were comparable to adult systemic exposure ranges. Dolutegravir/Lamivudine demonstrated efficacy and safety as initial ART in adolescents with HIV-1 through 48 weeks.

Establishment and evaluation of a predictive model for immune reconstitution in people living with HIV after antiretroviral therapy

BackgroundAchieving complete immune reconstitution (CIR) in people living with human immunodeficiency virus (PLWH) following antiretroviral therapy (ART) is essential for preventing acquired immunodeficiency syndrome (AIDS) progression and improving survival. However, there is a paucity of robust prediction models for determining the likelihood of CIR in PLWH after ART. We aimed to develop and validate a CIR prediction model utilizing baseline data.MethodsBaseline data including demographic information, immunological profiles, and routine laboratory test results, were collected from PLWH in Yunnan, China. Baseline referred to the first recorded results after HIV diagnosis but before initiating ART, and these initial measurements served as the baseline data for analysis. The participants were divided into training and validation sets (7:3 ratio). To construct the model and accompanying nomogram, univariable and multivariable Cox regression analyses were performed. The model was evaluated using the C-index, time-dependent receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves to assess discrimination, calibration, and clinical applicability.ResultsFive thousand four hundred eight PLWH were included, with a CIR of 38.52%. Cox regression analysis revealed various independent factors associated with CIR, including infection route, baseline CD4+T cell count, baseline CD4/CD8 ratio, interval from HIV diagnosis to ART initiation, and the level of PLT, Glu, Crea, HGB, ALT. A nomogram was formulated to predict the probability of achieving CIR at years 4, 5, and 6. The model demonstrated good performance, as evidenced by an AUC of 0.8 for both sets. Calibration curve analysis demonstrated a high level of agreement, and decision curve analysis revealed a significant positive yield.ConclusionsThis study successfully developed a prediction model with robust performance. This model has considerable potential to aid clinicians in tailoring treatment strategies, which could enhance outcomes and quality of life for PLWH.

Religion, Faith, and Spirituality as Barriers and Facilitators to Antiretroviral Therapy Initiation Among People with HIV in Indonesia.

Indonesia is a country deeply rooted in religion, faith, and spirituality. These aspects significantly determine individuals' decision-making and behavior, including health care decisions. Given the suboptimal attainment of the HIV-cascade targets in the country, we conducted a study to explore the role of religion, faith, and spirituality on antiretroviral therapy (ART) initiation. Our study involved individual interviews with 67 participants recruited from community health centers, public hospitals, and private clinics, predominantly Muslim, including 17 untreated people with HIV (ART-naïve), 30 people with HIV on treatment (ART-experienced), and 20 HIV service providers. Findings revealed that many individuals perceived HIV as a godly punishment related to individual failure (prior risk-prone behaviors), generating shame, guilt, and stigma. Perceiving religion as punitive and unforgiving and holding fatalistic beliefs was linked to postponed ART initiation. Conversely, perceiving religion as loving and forgiving, seeking forgiveness through religious practices, viewing ART intake as a "collaborative" effort with God, and engaging in righteous deeds facilitated ART initiation. These findings indicated that religion, faith, and spirituality can serve as both barriers and facilitators to ART initiation, depending on individuals' faith-based practices and perceptions of religion, whether punishing or forgiving. We recommend that people with HIV and health care providers better recognize the role of religion, faith, and spirituality in coping with shame, guilt, and stigma after an HIV diagnosis. This recognition can facilitate informed decisions regarding ART initiation, ultimately improving health outcomes for individuals with HIV in Indonesia.

Differentiated community-based point-of-care early infant diagnosis to improve HIV diagnosis and ART initiation among infants and young children in Zambia: a quasi-experimental cohort study

IntroductionAn estimated 800 000 children (<15 years) globally living with HIV remain undiagnosed. To reach these children with timely HIV testing services during infancy, we implemented a community-based differentiated care...

Prevalence and associated factors with low birth weight among human immunodeficiency virus exposed infants between 2004 and 2021 in Hubei, China: a retrospective cohort study

BackgroundLow birth weight (LBW, < 2500 g) is an essential indicator of neonatal death and poor infant development, but data on LBW among human immunodeficiency virus (HIV)-exposed infants in China is inadequate.ObjectiveThis study aimed to explore the temporal trend and factors associated with the LBW among HIV-exposed infants in Hubei province, China.MethodsThe pregnant women living with HIV in Hubei province, China between Jan 2004 and Dec 2021 were enrolled this study. Recruited HIV-positive women were provided with consultation about preventing mother-to-child transmission (PMTCT). The intervention measures for PMTCT were provided to pregnant women and HIV-exposed infants, and the LBW and HIV status of infants were followed. Collected data included women’s demographic information, HIV status of sexual partner, route of HIV transmission, HBV infection, HCV infection, syphilis infection, intrapartum CD4 count, whether received antiretroviral therapy (ART), the time of ART initiation, and ART regimens during pregnancy. Multivariable logistic regression was used to analyze factors associated with the LBW.ResultsIn total, 531 mothers (581 pregnancy events) and 581 infants were enrolled. The mean birth weight and LBW rate were 3075 ± 470.2 g and 8.4%, respectively. From 2004 to 2021, a significantly increased LBW rate (4.7–14.0%, P = .004) was observed. The use of protease inhibitor (PI)-based regimen (P = .04) and the exposure to ART in the first trimester (P = .01) were positively correlated with the increase of LBW rate. Exposure to ART in the first trimester (adjusted odds ratio [aOR] 3.64, 95%CI 1.29–10.27) and the second trimester (aOR 4.53, 95%CI 1.52–13.48), premature delivery (aOR 48.44, 95%CI 16.98-138.18), and infant with HIV infection (aOR 5.91, 95%CI 1.55–22.58) were predictors for LBW.ConclusionsThe significantly increased LBW rate in our study indicated that specific attention should be paid to HIV-exposed infants in China. More importantly, our study identified significant factors that can predict the risk of LBW. Interventions targeting these risk factors may prevent LBW among pregnant women living with HIV in future research and prenatal care.

Activation of CXCR3+ Tfh cells and B cells in lymph nodes during acute HIV-1 infection correlates with HIV-specific antibody development.

Early initiation of antiretroviral therapy (ART) is important to limit the seeding of the long-lasting HIV-1 reservoir; however, it also precludes the development of HIV-specific antibodies that can help control the virus if ART is stopped. Antibody development occurs within germinal centers in the lymph node and requires activation of both antigen-specific B cells and T follicular helper cells (Tfh), a specialized CD4+ cell that provides B cell help. To understand how early ART initiation may prohibit antibody development, we analyzed the frequencies and activation status of Tfh and B cells in lymph node biopsies collected in the different stages of acute HIV-1 infection. Our data suggest that decreased antibody development after early ART initiation may be due to limited germinal center development at the time of treatment and that new interventions that target activation of CXCR3+ Tfh may be beneficial to increase long-term HIV-specific antibody levels.

Human models that inform antiretroviral therapy-free remission with perinatally acquired HIV infection.

Rare persons who achieve disease-control despite high viral loads (viraemic nonprogressors) or maintain virologic control in the absence of antiretroviral therapy (ART) (elite controllers) or following ART interruption (posttreatment controllers) possess protective factors that can be harnessed for interventions to achieve ART-free remission. This review broadly summarizes these phenotypes in adults and children, and updates on findings important in informing strategies for ART-free remission in children with HIV. To date, only a few individual cases of posttreatment control have been described in children. Smaller HIV reservoir size with very early ART initiation in neonates with in-utero acquired HIV associates with improved virological and immunological outcomes. Nine new cases of ART-free remission in children were recently described - 4 from the P1115 trial, and 5 males from the Ucwaningo Lwabantwana study in South Africa. A striking reduction in the decay of intact proviruses was observed over three decades on suppressive ART in two early-treated twins with HIV. The unique environment of perinatal HIV infection favours effective restriction and decay of the HIV-1 reservoir with suppressive ART initiated very early. Sex and population differences require consideration in ongoing studies to inform ART-free remission.

Rapid initiation of antiretrovirals at a syringe services program for people with HIV who inject drugs

Background People who inject drugs (PWID) living with HIV are less likely to receive care at early disease stages and have low rates of viral suppression. This study examined the feasibility and acceptability of rapid antiretroviral therapy (ART) initiation among PWID with HIV at a syringe services program (SSP) and assessed retention in care after transition to a traditional HIV clinic. Patients/Materials and Methods A mixed-methods single-arm pilot study was conducted at an SSP in Miami, Florida. Participants with HIV viral load >200 copies/mL were immediately connected with an HIV care provider and received HIV care and peer navigation at the SSP for 6 months, then were transitioned to a traditional HIV clinic. Demographic data were abstracted from the SSP’s administrative records. Laboratory assessments and qualitative interviews were conducted at 1, 3, 6, 9, and 12 months. Results Sixty-nine percent, 70%, and 69% of participants were virally suppressed (<200 copies/mL) at 1, 3, and 6 months, respectively. Following transition to a traditional HIV clinic, viral suppression remained high at 74% and 79% at 9 and 12 months, respectively. Themes were identified on: 1) barriers to care in traditional HIV clinics, 2) the SSP as a ‘safe haven’, 3) benefits of the rapid ART initiation program, 4) acceptability of telehealth, and 5) persistent barriers to engaging in HIV care. Conclusion Rapid ART initiation for PWID at an SSP was acceptable and feasible and showed preliminary effectiveness in achieving HIV viral suppression and sustaining it after transition to a traditional HIV clinic.

Longitudinal changes in the transcriptionally active and intact HIV reservoir after starting ART during acute infection.

Even in antiretroviral therapy (ART)-suppressed human immunodeficiency virus (HIV)-infected individuals, there are heterogeneous populations of HIV-expressing cells exhibiting variable degrees of progression through blocks to HIV transcriptional initiation, elongation, completion, and splicing. These HIV-transcribing cells likely contribute to HIV-associated immune activation and inflammation as well as the viral rebound that occurs after stopping ART. However, it is unclear whether the blocks to HIV transcription are present before ART and how the timing and duration of ART may affect the clearance of cells expressing HIV transcripts that differ in their processivity and/or presence of mutations. To investigate these questions, we quantified different types of HIV transcripts and the corresponding HIV DNA regions/proviruses in longitudinal blood samples obtained before ART initiation (T1) and after 6 months (T2) and 1 year (T3) of ART in 16 individuals who initiated ART during acute HIV infection. Before ART, the pattern of HIV transcripts suggested blocks to elongation and splicing, and only ~10% of intact proviruses were transcribing intact HIV RNA. During the first 6 months of ART, we detected progressively greater reductions in initiated, 5'-elongated, mid-transcribed, completed, and multiply spliced HIV transcripts. Completed HIV RNA decayed faster than initiated or 5'-elongated HIV RNA, and intact HIV RNA tended to decay faster than defective HIV RNA. HIV DNA and RNA levels at T1-T3 correlated inversely with baseline CD4+ T-cell counts. Our findings suggest the existence of immune responses that act selectively to reduce HIV transcriptional completion and/or preferentially kill cells making completed or intact HIV RNA.IMPORTANCEEven in virologically suppressed HIV-infected individuals, expression of viral products from both intact and defective proviruses may contribute to HIV-associated immune activation and inflammation, which are thought to underlie the organ damage that persists despite suppressive ART. We investigated how the timing of ART initiation and the duration of ART affect the heterogeneous populations of HIV-transcribing cells, including a detailed characterization of the different HIV transcripts produced before ART and the rate at which they decay after ART initiation during acute HIV infection. Even during untreated infection, most cells (~90%) have blocks at some stage of transcription. Furthermore, different HIV transcripts decline at different rates on ART, with the fastest decay of cells making completed and intact HIV RNA. Our results suggest that intrinsic or extrinsic immune responses act selectively to either reduce particular stages of HIV transcription or cause selective killing of cells making particular HIV transcripts.