Late Antiretroviral Therapy Initiation Research Articles

The Problem of Late ART Initiation in Sub-Saharan Africa: A Transient Aspect of Scale-up or a Long-term Phenomenon?

Efforts to scale-up HIV care and treatment have been successful at initiating large numbers of patients onto antiretroviral therapy (ART), although persistent challenges remain to optimizing scale-up effectiveness in both resource-rich and resource-limited settings. Among the most important are very high rates of ART initiation in the advanced stages of HIV disease, which in turn drive morbidity, mortality, and onward transmission of HIV. With a focus on sub-Saharan Africa, this review article presents a conceptual framework for a broader discussion of the persistent problem of late ART initiation, including a need for more focus on the upstream precursors (late HIV diagnosis and late enrollment into HIV care) and their determinants. Without additional research and identification of multilevel interventions that successfully promote earlier initiation of ART, the problem of late ART initiation will persist, significantly undermining the long-term impact of HIV care scale-up on reducing mortality and controlling the HIV epidemic.

Structural Barriers to Timely Initiation of Antiretroviral Treatment in Vietnam: Findings from Six Outpatient Clinics

In Vietnam, premature mortality due to AIDS-related conditions is commonly associated with late initiation to antiretroviral therapy (ART). This study explores reasons for late ART initiation among people living with HIV (PLHIV) from the perspectives of health care providers and PLHIV. The study was undertaken in six clinics from five provinces in Vietnam. Baseline CD4 counts were collected from patient records and grouped into three categories: very late initiators (≤100 cells/mm3 CD4), late initiators (100–200 cells/mm3) and timely initiators (200–350 cells/mm3). Thirty in-depth interviews with patients who started ART and 15 focus group discussions with HIV service providers were conducted and thematic analysis of the content performed. Of 934 patients, 62% started ART very late and 11% initiated timely treatment. The proportion of patients for whom a CD4 count was obtained within six months of their HIV diagnosis ranged from 22% to 72%. The proportion of patients referred to ART clinics by voluntary testing and counselling centres ranged from 1% to 35%. Structural barriers to timely ART initiation were poor linkage between HIV testing and HIV care and treatment services, lack of patient confidentiality and a shortage of HIV/AIDS specialists. If Vietnam’s treatment practice is to align with WHO recommendations then the connection between voluntary counselling and testing service and ART clinics must be improved. Expansion and decentralization of HIV/AIDS services to allow implementation at the community level increased task sharing between doctors and nurses to overcome limited human resources, and improved patient confidentiality are likely to increase timely access to HIV treatment services for more patients.

Prevention of mother‐to‐child transmission of HIV in Latvia, 2008–2011

Purpose of the studyThe aim of this study was to describe trends in the management of pregnancies in HIV‐infected women and their outcomes, over a 4‐year period in Latvia on an Infectology Center of Latvia (LIC) basis.MethodsThe study of HIV‐infected women in Latvia giving birth to one or more children between 1 Jan 2008 and 31 Dec 2011.ResultsWe identified 199 HIV‐infected women with 210 pregnancies. Mean age was 27 years, median baseline pregnancy CD4 count was 452 cells/mm3, the baseline pregnancy plasma viral load (VL) was 53,066 copies/ml. Knowledge of HIV status before pregnancy was 60.5%, but 32.5% HIV‐positive diagnosis was confirmed during pregnancy and 7.1% after delivery. One pregnant woman's HIV disease progressed to AIDS and death. Women on antiretroviral therapy (ART) were 82.3%. Maternal monotherapy with the zidovudine (ZDV) rate was 10.4%, dual therapy with nucleoside reverse‐transcriptase inhibitor (NRTI) ‐ 2.3%, triple therapy with the protease‐inhibitor (PI) plus NRTI ‐ 87.3%. Median VL at delivery was 1349. A greater proportion of cases 91.5% had a VL <1000 copies/ml, from them 47.4% <40 copies/ml. Vaginal deliveries range was 20.8% of pregnancies and elective cesarean delivery 68.6%. Preterm delivery occurred in 12.1%. Overall mother‐to‐child transmission (MTCT) of HIV rate was 4.3%. Among the 35.5% of mothers initiating ART at 14 weeks’ gestation, MTCT was 1.4%, compared with 1.5% and 3.1% for those initiating ART at <14 weeks (n=67, 31.9%) and >24 weeks (n=32, 15.2%). Among 17.6% women, who did not receive prophylactic ART, MTCT rate was 16.2%. 7 of 9 women giving birth to an HIV‐positive child were diagnosed with HIV before pregnancy, 1 of 9 during pregnancy, 1 of 9 after delivery. From women giving birth to an HIV‐positive child 6 did not receive prophylactic ART, 1 started ART at week 14, 2 after week 14.ConclusionsWomen's low education, recurrent pregnancies, intravenous drug use, vaginal deliveries, not receiving and late initiation of prophylactic ART was independently (p<0.05) associated with an increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV‐ infected women (also HIV status identification twice during pregnancy). Management of pregnancies in HIV‐infected women according to the LIC guidelines, i.e. ART from week 14, intravenous ZDV during labour, elective cesarean delivery, neonatal ZDV during 6 weeks and no breastfeeding is effective to reduce risk for MTCT.

1.0 Introduction

1.0 Introduction

Profil clinicobiologique, thérapeutique et évolutif des patients infectés par le VIH hospitalisés au service des maladies infectieuses et tropicales d’Abidjan (Côte d’Ivoire)

The objective of this study is to describe the clinical, biological, therapeutic and evolving current profile of hospitalized patients with HIV infection in the cohort of the Infectious and Tropical Diseases Unit (ITDU) in the aim to improve their care management. This is a retrospective study, conducted on medical data of hospitalized cases of patients with HIV infection in the ITDU at the teaching hospital of Treichville (Abidjan) from 2006 to 2007. During the two years, 447 patients were included in the study. Their average age was 39 years [18 years-86 years] and sex ratio was 0.69. Of the 447 patients, 35% were unemployed and 67% were new patients who had never undergone antiretroviral therapy (ART). The duration of drug exposure was less than 6 months in 59% of treated patients. The average time to initiate ART was seven weeks. Among naive patients 41.9% were lost to follow up, 35.9% were waiting for treatment and 22.1% waiting for baseline biological test to initiate ART. At the initiation of ART, 79.6% of patients had a CD4 count less than 200/mm3. The reasons of hospitalization defining AIDS were dominated by tuberculosis (34.2%), cerebral toxoplasmosis (17.9%) and neuromeningeal cryptococcosis (8%). The main reasons of hospitalization in classifying non-AIDS were pyelonephritis (6.5%), bacterial pneumonia (5.4%) and undetermined infectious encephalitis (4.9%). Hospital mortality was 24.4%. The leading causes of death were tuberculosis (22.9%), cerebral toxoplasmosis (20.2%), undetermined infectious encephalitis (18.3%) and cryptococcal meningitis (13.7%). The profile of PLHIV in hospital is characterized by profound immunosuppression due to late diagnosis and high mortality associated with severe opportunistic infections and late initiation of ART

Factors Associated with Late Antiretroviral Therapy Initiation among Adults in Mozambique

BackgroundDespite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission.MethodsTo evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count<100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation.ResultsThe proportion of patients initiating ART late decreased from 46% to 37% during 2005–2007, but remained constant (between 37–33%) from 2007–2009. Of those who initiated ART late (median CD4 = 57 cells/µL), 5% were known to have died and 54% were lost to clinic within 6 months of ART initiation (compared with 2% and 47% among other patients starting ART [median CD4 = 192 cells/µL]). In multivariate analysis, female sex and pregnancy at ART initiation (AORfemale_not_pregnant_vs._male = 0.66, 95%CI [0.62–0.69]; AORpregnant_vs._non_pregnant = 0.60, 95%CI [0.49–0.73]), younger and older age (AOR15–25_vs.26–30 = 0.86, 95%CI [0.79–0.94], AOR>45_vs.26–30 = 0.72, 95%CI [0.67–0.77]), entry into care via PMTCT (AORentry_through_PMTCT_vs.VCT = 0.42, 95%CI [0.35–0.50]), marital status (AORmarried/in union_vs.single = 0.87, 95%CI [0.83–0.92]), education (AORsecondary_or_higher_vs.primary = 0.87, 95%CI [0.83–0.93]) and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AORCD4_machine_onsite_vs.offsite = 0.83, 95%CI [0.74–0.94]) and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77–0.93]).Conclusion:The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.

Non-Disclosure of a Pregnant Woman’s HIV Status to Her Partner is Associated with Non-Optimal Prevention of Mother-to-Child Transmission

Our objective was to study relations between non-disclosure of HIV to partner, socio demographics and prevention of HIV mother-to-child transmission (PMTCT), among HIV-infected pregnant women enrolled in the French Perinatal Cohort (ANRS-EPF-CO1) from 2005 to 2009 (N = 2,952). Fifteen percent of the women did not disclose their HIV status to their partner. Non-disclosure was more frequent in women diagnosed with HIV infection late in pregnancy, originating from Sub-Saharan Africa or living alone, as well as when the partner was not tested for HIV. Non-disclosure was independently associated with non optimal PMTCT: late initiation of antiretroviral therapy, detectable viral load at delivery and lack of neonatal prophylaxis. Nonetheless, the rate of transmission did not differ according to disclosure status. Factors associated with non-disclosure reflect vulnerability and its association with non optimal PMTCT is a cause for concern although the impact on transmission was limited in this context of universal free access to care.

Lack of pre-antiretroviral care and competition from traditional healers, crucial risk factors for very late initiation of antiretroviral therapy for HIV - A case-control study from eastern Uganda

Although WHO recommends starting antiretroviral treatment at a CD4 count of 350 cells/[µ]L, many Ugandan districts still struggle with large proportions of clients initiating ART very late at CD4<50 cells/[µ]L. This study seeks to establish crucial risk factors for very late ART initiation in eastern Uganda. All adult HIV-infected clients on ART in Iganga who enrolled between 2005 and 2009 were eligible for this case-control study. Clients who started ART at CD4 cell count of <50 cells/[µ]L (very late initiators) were classified as cases and 50-200 cells/[µ]L (late initiators) as control subjects. A total of 152 cases and 202 controls were interviewed. Multivariate analyses were performed to calculate adjusted odds ratios and 95% confidence intervals. Reported health system-related factors associated with very late ART initiation were stock-outs of antiretroviral drugs stock-outs (affecting 70% of the cases and none of the controls), competition from traditional/spiritual healers (AOR 7.8, 95 CI% 3.7-16.4), and lack of pre-ARV care (AOR 4.6, 95% CI: 2.3-9.3). Men were 60% more likely and subsistence farmers six times more likely (AOR 6.3, 95% CI: 3.1-13.0) to initiate ART very late. Lack of family support tripled the risk of initiating ART very late (AOR 3.3, 95% CI: 1.6-6.6). Policy makers should prevent ARV stock-outs though effective ARV procurement and supply chain management. New HIV clients should seek pre-ARV care for routine monitoring and determination of ART eligibility. ART services should be more affordable, accessible and user-friendly to make them more attractive than traditional healers.

Lack of pre-antiretroviral care and competition from traditional healers, crucial risk factors for very late initiation of antiretroviral therapy for HIV - A case-control study from eastern Uganda

Lack of pre-antiretroviral care and competition from traditional healers, crucial risk factors for very late initiation of antiretroviral therapy for HIV - A case-control study from eastern Uganda

Antiretroviral therapy: a promising HIV prevention strategy?

The use of antiretroviral therapy (ART) has been associated with significant improvement in morbidity and survival of persons living with HIV. In addition, recently, there has also been intense interest in the potential impact of ART on HIV transmission and consequently on the trajectory of the HIV epidemic globally. Evidence from mathematical modeling analyses and observational and ecological studies supports the potential for ART as prevention. However, definitive data from clinical trials are awaited. In the United States, the feasibility and potential of using ART as a prevention strategy presents particular challenges: the large number of individuals with undiagnosed HIV; the predominance of disenfranchised individuals affected by the epidemic; evidence of delay in engagement in HIV care after diagnosis with attendant late initiation of ART; and difficulties with consistent long-term adherence to ART and concerns regarding long-term risk-behavior change. Thus, for this novel effort to succeed, a multidimensional approach is necessary that must include policy changes, social mobilization, and improved access to clinical and supportive services for persons living with HIV, with a particular focus on the unique needs of at-risk populations, combined with engagement of all cadres of health care providers and community constituencies.

Abstract 5096: Early versus Late Initiation of Antiretroviral Therapy and Arterial Stiffness in HIV Infection

Background: HIV infection is associated with increased rates of cardiovascular disease. Assessment of arterial stiffness via pulse wave velocity (PWV) is strongly associated with cardiovascular risk, and prior studies have shown that HIV-infected patients have higher stiffness compared to controls. Current guidelines recommend initiation of antiretroviral therapy at a CD4 T cell count of 350 cells/ul. Whether earlier initiation of HIV therapy has any effect on cardiovascular risk as assessed by PWV is unknown. Methods: We conducted a cross-sectional study of 81 HIV-infected men who were antiretroviral-treated with undetectable plasma HIV RNA levels. Subjects underwent noninvasive assessment of PWV using the SphygmoCor System (AtCor Medical, Australia). A generalized linear model was used to determine the relationship between traditional cardiovascular risk factors, HIV-related predictors, and arterial stiffness as measured by PWV. Results: The median age was 47 years (IQR 43–54), 36% had a history of hypertension, and 46% had hypercholesterolemia. The median current CD4 T cell count was 539 cells/ul (IQR 324 –736), and nadir CD4 count was 180 cells/ul (IQR 29 –311). The median PWV was 5.3 m/s (IQR 4.9 – 6.2). In unadjusted analyses, age, diabetes, current CD4 count and nadir CD4 count &lt;350 were predictors of PWV (all p &lt;0.05). After adjusting for both traditional cardiovascular risk factors (age, systolic and diastolic BP, hypertension, diabetes, hypercholesterolemia, smoking) and HIV-related covariates, a nadir CD4 count &lt;350 remained independently associated with a 0.58 m/s increase in PWV (95% CI 0.15–1.01, p&lt;0.008). Other significant determinants of PWV in multivariate analyses included age, systolic and diastolic BP, and diabetes. Of note, neither duration of antiretroviral therapy nor exposure to protease inhibitors was associated with degree of arterial stiffness. Conclusions: Among treated HIV-infected individuals, higher PWV is independently associated with both traditional cardiovascular risk factors including age and diabetes, as well as low nadir CD4 count. Our data support the concept that initiation of antiretroviral therapy before low CD4 counts occur may reduce cardiovascular risk among individuals with HIV infection.

Life-threatening immune reconstitution inflammatory syndrome after Pneumocystis pneumonia: a cautionary case series

Life-threatening immune reconstitution inflammatory syndrome after Pneumocystis pneumonia: a cautionary case series

Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study

To investigate delayed HIV diagnosis and late initiation of antiretroviral therapy (ART) in the Swiss HIV Cohort Study. Two sub-populations were included: 1915 patients with HIV diagnosis from 1998 to 2007 and within 3 months of cohort registration (group A), and 1730 treatment-naïve patients with CD4>or=200 cells/microL before their second cohort visit (group B). In group A, predictors for low initial CD4 cell counts were examined with a median regression. In group B, we studied predictors for CD4<200 cells/microL without ART despite cohort follow-up. Median initial CD4 cell count in group A was 331 cells/microL; 31% and 10% were <200 and <50 cells/microL, respectively. Risk factors for low CD4 count were age and non-White race. Homosexual transmission, intravenous drug use and living alone were protective. In group B, 30% initiated ART with CD4>or=200 cells/microL; 18% and 2% dropped to CD4 <200 and <50 cells/microL without ART, respectively. Sub-Saharan origin was associated with lower probability of CD4 <200 cells/microL without ART during follow-up. Median CD4 count at ART initiation was 207 and 253 cells/microL in groups A and B, respectively. CD4<200 cells/microL and, particularly, CD4<50 cells/microL before starting ART are predominantly caused by late presentation. Earlier HIV diagnosis is paramount.

HIV update: Emerging clinical evidence and a review of recommendations for the use of highly active antiretroviral therapy

This supplement will focus on recent trial data concerning the efficacy of certain nucleoside reverse transcriptase inhibitor (NRTI)-based highly active antiretroviral therapy (HAART) regimens, the most recent guidelines from the Department of Health and Human Services (DHHS) for the timing of antiretroviral (ARV) therapy initiation, and recommended ARV drug classes for managing treatment-naïve patients with HIV. When choosing an initial regimen for the treatment of HIV, it is important to carefully consider therapeutic goals. These goals include choosing HAART that is likely to maximally suppress viral replication, maintain or restore immunologic function, improve quality of life, and reduce HIV-related morbidity and mortality. The evidence-based DHHS guidelines recommend HAART regimens that are non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based. DHHS, however, does not recommend the use of triple-NRTI therapy for the initial treatment of HIV unless a preferred or alternative NNRTI- or PI-based regimen cannot be used. This recommendation concerning triple-NRTI therapy is supported by results from recent trials that demonstrated inferior outcomes with triple-NRTI-containing regimens compared with NNRTI- or PI-based HAART regimens. The timing for initiation of ARV therapy continues to change over time as the DHHS guidelines have evolved. Although the benefits of initiating ARV when CD4 cell count is < 200 cells/mm3 are well established, the use of early versus late initiation of ARV therapy in patients with CD4 cell counts > 200 cells/mm3 has its own benefits and drawbacks. To successfully manage people with HIV, it is crucial to find a balance between ARV potency, tolerability, safety, and convenience while providing durable viral suppression.