Timing Of Antiretroviral Therapy Initiation Research Articles

Delay in the Provision of Antiretroviral Therapy to HIV-infected TB Patients in Nigeria.

BackgroundNigeria has a high burden of HIV and tuberculosis (TB). To reduce TB-associated morbidity and mortality, the World Health Organization recommends that HIV-positive TB patients receive antiretroviral therapy (ART) within eight weeks of TB treatment initiation, or within two weeks if profoundly immunosuppressed (CD4<50 cell/μL).MethodsTB and HIV clinical records from facilities in two Nigerian states between October 1st, 2012 and September 30th, 2013 were retrospectively reviewed to assess uptake and timing of ART initiation among HIV-positive TB patients. Healthcare workers were qualitatively interviewed to assess TB/HIV knowledge and barriers to timely ART.ResultsData were abstracted from 4,810 TB patient records, of which 1,249 (26.0%) had HIV-positive or unknown HIV status documented, and the 574 (45.9%) HIV-positive TB patients were evaluated for timing of ART uptake relative to TB treatment. Among 484 (84.3%) HIV-positive TB patients not already on ART, 256 (52.9%, 95% CI: 45.0–60.8) were not initiated on ART during six months of TB treatment. 30.0% of 273 patients with a known CD4≥50cells/μL started ART within eight weeks, and 14.8% of 54 patients with a known CD4<50cells/μL started within the recommended two weeks. Only 42% of health workers interviewed reported knowing to interpret guidelines on when to initiate ART in HIV-positive TB patients based on CD4 cell count results. CD4 cell count significantly predicted timely ART uptake.ConclusionA large proportion of HIV-positive TB patients were not initiated on ART early or even at all during TB treatment. Retraining of staff, and interventions to strengthen referral systems should be implemented to ensure timely provision of ART among HIV-positive TB patients in Nigeria.

Anthropometric Improvement among HIV Infected Pre-School Children Following Initiation of First Line Anti-Retroviral Therapy: Implications for Follow Up.

BackgroundAntiretroviral therapy (ART) is a lifesaving intervention for HIV infected children. There is a scarcity of data on immunological recovery and its relation with growth indicators among HIV infected young children. The current study aims to assess the pattern of anthropometric Z-score improvement following initiation of first-line ART among under-five children and the relationship between anthropometric Z-score improvement and immunologic recovery.MethodsWe included under-five children who were on first-line ART at five major hospitals in Addis Ababa, Ethiopia. We measured anthropometry and collected clinical and laboratory data at follow up, and we retrieved clinical and anthropometric data at ART initiation from records. Z-scores for each of the anthropometric indices were calculated based on WHO growth standards using ENA for SMART 2011 software. Linear regression was used to assess the relationship between time on ART and anthropometric Z-score improvement; and the relationship between anthropometric Z-score improvement and immunologic recovery. Multiple linear regression was used to assess the independent predictors of anthropometric Z-score change.ResultsThe median age of the participants was 4.1 (Interquartile range (IQR): 3.3–4.9) years. More than half (52.48%) were female. The median duration of follow up was 1.69 (IQR: 1.08–2.63) years. There was a significant improvement in all anthropometric indices at any follow up after initiation of first-line ART (underweight; 39.5% vs16.5%, stunting; 71.3% vs 62.9% and wasting; 16.3% vs 1.0%; p-value< 0.0001). There was an inverse relationship between improvement in weight for age Z-score (WAZ) and duration of ART (R2 = 0.04; F (1, 158); p = 0.013). Height for age Z-score (HAZ) both at the time of ART initiation and follow up has a positive linear relationship with CD4 percentage at follow up (Coef. = 1.92; R2 = 0.05; p-value = 0.002). Duration on ART (Std. Err. = 0.206, t = -1.99, p-value = 0.049) and level of maternal education (Std. Err. = 0.290, t = 2.64, p-value = 0.009) were the only independent predictors of the change in WAZ and change in HAZ at any follow up visit respectively.ConclusionThere was a significant improvement in all anthropometric indices at any follow-up after initiation of first-line ART among under-five children. HAZ was linearly related with immunologic recovery following ART initiation. The findings indicate that anthropometric indices could be taken as proxy indicators of immunologic recovery for under-five children.

Optimizing Infant HIV Diagnosis in Resource-Limited Settings: Modeling the Impact of HIV DNA PCR Testing at Birth.

Early antiretroviral therapy (ART) initiation in HIV-infected infants significantly improves survival but is often delayed in resource-limited settings. Adding HIV testing of infants at birth to the current recommendation of testing at age 4-6 weeks may improve testing rates and decrease time to ART initiation. We modeled the benefit of adding HIV testing at birth to the current 6-week testing algorithm. Microsoft Excel was used to create a decision-tree model of the care continuum for the estimated 1,400,000 HIV-infected women and their infants in sub-Saharan Africa in 2012. The model assumed average published rates for facility births (42.9%), prevention of mother-to-child HIV transmission utilization (63%), mother-to-child-transmission rates based on prevention of mother-to-child HIV transmission regimen (5%-40%), return of test results (41%), enrollment in HIV care (52%), and ART initiation (54%). We conducted sensitivity analyses to model the impact of key variables and applied the model to specific country examples. Adding HIV testing at birth would increase the number of infants on ART by 204% by age 18 months. The greatest increase is seen in early ART initiations (543% by age 3 months). The increase would lead to a corresponding increase in survival at 12 months of age, with 5108 fewer infant deaths (44,550, versus 49,658). Adding HIV testing at birth has the potential to improve the number and timing of ART initiation of HIV-infected infants, leading to a decrease in infant mortality. Using this model, countries should investigate a combination of HIV testing at birth and during the early infant period.

Timing of initiation of antiretroviral therapy and adverse pregnancy outcomes: a systematic review and meta-analysis

Although lifelong combination antiretroviral therapy (ART) is recommended for all individuals with HIV, few data exist for pregnancy outcomes associated with ART initiation before conception. We assessed adverse pregnancy outcomes associated with ART initiated before conception compared with that of ART started after conception. We did a systematic review of studies from low-income, middle-income, and high-income countries by searching the Cochrane Central Register of Controlled Trials, Embase, LILACS, MEDLINE, Toxline, Web of Knowledge, and WHO Global Index Medicus and trials in progress (International Clinical Trials Registry Platform) for randomised trials, quasi-randomised trials, and prospective cohort studies done between Jan 1, 1980, and June 1, 2016, in which timing of ART initiation in pregnant women living with HIV was reported. We used the risk ratio (RR) and corresponding 95% CIs as the primary measure to assess the association between the selected outcomes and ART initiation before conception versus after conception. We used a random-effects model to pool risk ratios. We included 11 studies with 19 189 mother-infant pairs. Women who started ART before conception were significantly more likely to deliver preterm (pooled RR 1·20, 95% CI 1·01-1·44) or very preterm (1·53, 1·22-1·92), or to have low-birthweight infants (1·30, 1·04-1·62) than were those who began ART after conception. Few data exist for neonatal mortality. The risk of very low birthweight, small for gestational age, severe small for gestational age, stillbirth, and congenital anomalies did not differ significantly between women who were taking ART before conception and those who began ART after conception. The benefits of ART for maternal health and prevention of perinatal transmission outweigh risks, but data for the extent and severity of these risks are scarce and of low quality. As use of ART before conception rapidly increases globally, monitoring for potential adverse pregnancy outcomes will be crucial. WHO.

Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial

Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per μL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per μL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367. Between March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30-44), CD4 T-cell count 648 per μL (583-767), and HIV plasma viral load 4·2 log10 copies per mL (3·5-4·7). 29% were female and 28% were current smokers. Median follow-up time was 2·0 years (IQR 1·9-3·0). We noted no differences in FEV1 slopes between the immediate and deferred ART groups either in smokers (difference of -3·3 mL/year, 95% CI -38·8 to 32·2; p=0·86) or in non-smokers (difference of -5·6 mL/year, -29·4 to 18·3; p=0·65) or in pooled analyses adjusted for smoking status at each study visit (difference of -5·2 mL/year, -25·1 to 14·6; p=0·61). The timing of ART initiation has no major short-term effect on rate of lung function decline in HIV-positive individuals who are naive to ART, with CD4 T-cell counts of more than 500 per μL. In light of updated WHO recommendations that all HIV-positive individuals should be treated with ART, regardless of their CD4 T-cell count, our results suggest an absence of significant pulmonary harm with such an approach. US National Heart Lung and Blood Institute, US National Institute of Allergy and Infectious Diseases, Division of AIDS, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), Australian National Health and Medical Research Council, Danish National Research Foundation, European AIDS Treatment Network, German Ministry of Education and Research, UK Medical Research Council and National Institute for Health Research, and US Veterans Health Administration Office of Research and Development.

Pulmonary effects of timing of antiretroviral therapy initiation

Pulmonary effects of timing of antiretroviral therapy initiation

Using HIV Viral Load From Surveillance to Estimate the Timing of Antiretroviral Therapy Initiation.

HIV surveillance programs do not typically collect comprehensive data on antiretroviral therapy (ART). We validated a population-based measure of ART initiation that uses HIV viral load (VL) results in the absence of data on ART. We used CD4/VL data reported to NYC HIV Surveillance for persons aged ≥13 years and diagnosed with HIV from 2006 to 2012 to validate estimates of ART initiation date based on 3 ART initiation definitions: (1) ≥1-log decline in copies per milliliter between 2 VLs over 3 months; (2) ≥2-log decline in copies per milliliter between 2 VLs over 3 months; and (3) the earliest of either a ≥1-log decline in VL over 3 months, or a change from detectable VL to undetectable VL (<400 copies/mL) over any interval. We plotted median CD4 counts by quarter before and after ART initiation to compare estimated initiation date with nadir of the CD4 trajectory. A total of 24,348 persons were diagnosed with HIV in NYC from 2006 to 2012. In all, 12,123 persons had probable ART initiation based on ≥2-log decline, 12,719 based on ≥1-log decline, and 14,311 based on ≥1-log decline or detectable-undetectable change. Lowest median CD4 count occurred at the estimated ART initiation date for all 3 definitions. The definition based on a ≥1-log VL decline or a change from detectable to undetectable VL captured more ART initiations and identified earlier initiation dates. Serial VL measures are a valid source for estimating ART initiation. A definition that includes a ≥1-log VL decline or a change from detectable to undetectable VL performed best.

Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing.

Fractional anisotropy in the frontal white matter, corpus callosum, and internal capsule is abnormal in human immunodeficiency virus-positive (HIV+) adults. We describe the distribution and nature of white matter abnormalities in a cohort of children who started antiretroviral therapy within the first year of life and the benefit of early treatment by using DTI measures (fractional anisotropy and mean, axial, and radial diffusion). DTI was performed on children in a neurodevelopmental substudy from the Children with HIV Early Antiretroviral trial. Voxel-based group comparisons were obtained to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children. Associations of DTI parameters with the timing of antiretroviral therapy initiation were examined. Thirty-nine HIV+ children (15 boys; mean age, 5.4 years) and 13 controls (5 boys; mean age, 5.7 years) were scanned. Two clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group, with symmetric distribution predominantly due to increased radial diffusion, suggestive of decreased myelination. Corticospinal tracts rather than the corpus callosum were predominantly involved. Children on early-interrupted antiretroviral therapy had lower fractional anisotropy compared with those receiving continuous treatment. HIV+ children at 5 years of age have white matter abnormalities measured by fractional anisotropy, despite early antiretroviral therapy, suggesting that early antiretroviral therapy does not fully protect the white matter from either peripartum or in utero infection. In contrast to adults, the corticospinal tracts are predominantly involved rather than the corpus callosum, possibly due to early antiretroviral therapy. Continuous early antiretroviral therapy can limit white matter damage.

Accelerating the Uptake and Timing of Antiretroviral Therapy Initiation in Sub-Saharan Africa: An Operations Research Agenda.

Sydney Rosen and colleagues describe an operations research agenda to accelerating uptake of HIV treatment initiation.

A retrospective study of HIV, antiretroviral therapy, and pregnancy-associated hypertension among women in Lusaka, Zambia

ObjectiveTo investigate the association between HIV, antiretroviral therapy (ART), and pregnancy-associated hypertension (PAH) in an HIV-endemic setting. MethodsA retrospective cohort study was undertaken of pregnant women for whom information was recorded between February 2006 and December 2012 in the Zambia Electronic Perinatal Record System, which captures data from 25 facilities in Lusaka, Zambia. PAH was defined as eclampsia, pre-eclampsia, hypertension, or elevated blood pressure (>140/80mm Hg) during delivery admission. Logistic regression estimated the odds of PAH among women by HIV serostatus, and by most recent CD4 T lymphocyte count and ART status among women with HIV infection. ResultsAmong 249 771 women included in the analysis, 5354 (2.1%) had PAH. Compared with women without HIV infection, women with HIV infection not receiving ART had lower odds of PAH (adjusted odds ratio [AOR] 0.86, 95% confidence interval 0.78–0.95), whereas those with HIV infection who had initiated ART had higher odds of PAH (AOR 1.15, 95% CI 1.01–1.32). No association was found between PAH and timing of ART initiation or CD4 lymphocyte count. ConclusionIn a large African urban cohort, women with untreated HIV infection had the lowest odds of PAH. Treatment with ART could increase PAH risk beyond that of women without HIV infection and those with untreated infection.

POC CD4 Testing Improves Linkage to HIV Care and Timeliness of ART Initiation in a Public Health Approach: A Systematic Review and Meta-Analysis.

BackgroundCD4 cell count is an important test in HIV programs for baseline risk assessment, monitoring of ART where viral load is not available, and, in many settings, antiretroviral therapy (ART) initiation decisions. However, access to CD4 testing is limited, in part due to the centralized conventional laboratory network. Point of care (POC) CD4 testing has the potential to address some of the challenges of centralized CD4 testing and delays in delivery of timely testing and ART initiation. We conducted a systematic review and meta-analysis to identify the extent to which POC improves linkages to HIV care and timeliness of ART initiation.MethodsWe searched two databases and four conference sites between January 2005 and April 2015 for studies reporting test turnaround times, proportion of results returned, and retention associated with the use of point-of-care CD4. Random effects models were used to estimate pooled risk ratios, pooled proportions, and 95% confidence intervals.ResultsWe identified 30 eligible studies, most of which were completed in Africa. Test turnaround times were reduced with the use of POC CD4. The time from HIV diagnosis to CD4 test was reduced from 10.5 days with conventional laboratory-based testing to 0.1 days with POC CD4 testing. Retention along several steps of the treatment initiation cascade was significantly higher with POC CD4 testing, notably from HIV testing to CD4 testing, receipt of results, and pre-CD4 test retention (all p<0.001). Furthermore, retention between CD4 testing and ART initiation increased with POC CD4 testing compared to conventional laboratory-based testing (p = 0.01). We also carried out a non-systematic review of the literature observing that POC CD4 increased the projected life expectancy, was cost-effective, and acceptable.ConclusionsPOC CD4 technologies reduce the time and increase patient retention along the testing and treatment cascade compared to conventional laboratory-based testing. POC CD4 is, therefore, a useful tool to perform CD4 testing and expedite result delivery.

Diagnosis of HIV-Associated Oral Lesions in Relation to Early versus Delayed Antiretroviral Therapy: Results from the CIPRA HT001 Trial.

Oral mucosal lesions that are associated with HIV infection can play an important role in guiding the decision to initiate antiretroviral therapy (ART). The incidence of these lesions relative to the timing of ART initiation has not been well characterized. A randomized controlled clinical trial was conducted at the GHESKIO Center in Port-au-Prince, Haiti between 2004 and 2009. 816 HIV-infected ART-naïve participants with CD4 T cell counts between 200 and 350 cells/mm3 were randomized to either immediate ART initiation (early group; N = 408), or initiation when CD4 T cell count was less than or equal 200 cells/mm3 or with the development of an AIDS-defining condition (delayed group; N = 408). Every 3 months, all participants underwent an oral examination. The incidence of oral lesions was 4.10 in the early group and 17.85 in the delayed group (p-value <0.01). In comparison to the early group, there was a significantly higher incidence of candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex in the delayed group. The incidence of oral warts in delayed group was 0.97 before therapy and 4.27 post-ART initiation (p-value <0.01). In the delayed group the incidence of oral warts post-ART initiation was significantly higher than that seen in the early group (4.27 versus 1.09; p-value <0.01). The incidence of oral warts increased after ART was initiated, and relative to the early group there was a four-fold increase in oral warts if ART was initiated following an AIDS diagnosis. Based upon our findings, candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex indicate immune suppression and the need to start ART. In contrast, oral warts are a sign of immune reconstitution following ART initiation.

Impact of HIV-1 tropism on the emergence of non-AIDS events in HIV-infected patients receiving fully suppressive antiretroviral therapy.

Objective:The impact of HIV-1 tropism on the emergence of non-AIDS events was evaluated in a cohort of 116 antiretroviral therapy (ART) responder patients.Methods:The patients were followed for the emergence of hypertension, renal impairment, metabolic and bone disorders (defined as non-AIDS events) each 8 weeks at standard visits. A V3 plasma sequence genotype analysis was performed at the time of ART initiation and the geno2pheno algorithm with the results that defines the false-positive rate (FPR) was used to infer HIV tropism. The associations between the non-AIDS events and the FPR at baseline were evaluated using the χ2 test for trend. A Cox-regression analysis using the counting process formulation of Andersen and Gill was performed to define whether the emergence of non-AIDS events was correlated to FPR.Results:The prevalence of at least one non-AIDS event resulted higher in patients with a FPR below 10% than in patients with a R5 virus (P = 0.033). Patients with a FPR below 5.0% most frequently developed non-AIDS events during ART (P = 0.01). A higher prevalence of patients with at least two AIDS events was found in the group of patients with a FPR below 5.0% with respect to the others (P < 0.001). At multivariate Cox-regression analysis, having an X4 virus and age were independently associated with a higher probability of non-AIDS event development.Conclusion:This study shows that an X4 virus, particularly a FPR less than 5%, is related to non-AIDS events development. Further studies are warranted to understand the mechanisms underlying this phenomenon.

A Systematic Review of Interventions to Reduce Maternal Mortality among HIV-Infected Pregnant and Postpartum Women

In high-prevalence populations, HIV-related maternal mortality is high with increased mortality found among HIV-infected pregnant and postpartum women compared to their uninfected peers. The scale-up of HIV-related treatment options and broader reach of programming for HIV-infected pregnant and postpartum women is likely to have decreased maternal mortality. This systematic review synthesized evidence on interventions that have directly reduced mortality among this population. Studies published between January 1, 2003 and November 30, 2014 were searched using PubMed. Of the 1,373 records screened, 19 were included in the analysis. Interventions identified through the review include antiretroviral therapy (ART), micronutrients (multivitamins, vitamin A, and selenium), and antibiotics. ART during pregnancy was shown to reduce mortality. Timing of ART initiation, duration of treatment, HIV disease status, and ART discontinuation after pregnancy influence mortality reduction. Incident pregnancy in women already on ART for their health appears not to have adverse consequences for the mother. Multivitamin use was shown to reduce disease progression while other micronutrients and antibiotics had no beneficial effect on maternal mortality. ART was the only intervention identified that decreased death in HIV-infected pregnant and postpartum women. The findings support global trends in encouraging initiation of lifelong ART for all HIV-infected pregnant and breastfeeding women (Option B+), regardless of their CD4+ count, as an important step in ensuring appropriate care and treatment. Maternal mortality is a rare event that highlights challenges in measuring the impact of interventions on mortality. Developing effective patient-centered interventions to reduce maternal morbidity and mortality, as well as corresponding evaluation measures of their impact, requires further attention by policy makers, program managers, and researchers.

START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection.

The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed.

Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy.

Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study. Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/μL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA. In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors.

Timing of antiretroviral therapy initiation after diagnosis of recent human immunodeficiency virus infection and CD4+ T-cell recovery

We retrospectively examined the timing of antiretroviral therapy (ART) initiation and CD4+ T-cell recovery over 36 months among recent human immunodeficiency virus (HIV) infections using BED (HIV-1 subtypes B, E and D) immunoglobulin G capture enzyme immunoassay (BED-CEIA). Regardless of baseline CD4+ counts, individuals (n = 393) who initiated ART >2 months after diagnosis had significantly decreased probability and rate of achieving CD4+ counts ≥900 cells/μL or ≥600 cells/μL than those individuals (n = 135) who started ART earlier (≤2 months). But the mean CD4+ counts in two groups converged after 30 months of treatment. Early ART initiation leads to accelerated CD4+ recovery, but does not offer a long-term advantage in CD4+ counts.

Highlights of the third edition of Chinese guidelines for AIDS diagnosis and treatment(2015)

The third edition of Chinese guidelines for AIDS diagnosis and treatment was launched in 2015 by AIDS Professional Group, Society of Infectious Diseases, Chinese Medical Association. New edition emphasizes the importance of timely initiation of anti-retroviral therapy(ART). Like other guidelines, this edition recommends that once the HIV infection is confirmed, the ART should be initiated timely. For patients with HIV and opportunistic infections, once the infections are under control, the ART should be initiated without delay. For AIDS patients complicated with tuberculosis whose CD4 cell counts are less than 200/μL, the ART should start within 2 weeks after the initiation of anti-tuberculosis treatment. In this guideline, the drugs with severe toxicities and poor tolerance are excluded, and new drugs are added such as rilpivrine (RPV) and atazanavir (ATV) because of less toxicity and higher HIV depression effect; and 3TC+TDF+EFV is recommended as the first line regimen. As for children with HIV infection, especially for those less than 5 years, once the infection is confirmed the ART should be initiated immediately. For the prevention of HIV mother to children transmission, new edition recommends that HIV-infected pregnant women start ART early and keep on ART all their lives.

Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18–24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 <350 (n = 59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

Immune recovery among HIV-infected patients in northwestern Tanzania after 2 years of anti-retroviral therapy use: a retrospective cohort study

Background: The use of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) is associated with significant and sustained decrease in the viral RNA levels that allows the immune system to recover. The extent of this immune recovery depends on the baseline CD4 count. Evidence on the extent of immune recovery in patients with advanced HIV from resource limited settings is scarce. The objective of this study was to determine immune recovery in a cohort of HIV infected outpatients after using ART for a period of 2 years. Methods: This retrospective cohort study was conducted in an outpatient HIV clinic at Bugando Medical Centre in northwestern Tanzania. CD4+ T-cell counts for HIV-positive adults at the time of enrolment were measured and retrospectively followed up during ART eligibility screening process prior to initiation of antiretroviral (ARV) drugs. We then compared the CD4+ T-cell counts at baseline and that during the enrolment. Results: A total of 238 patients files were screened for enrolment. Of the 238 patients, 171 (71.8%) fulfilled the criteria and were enrolled for the study. The lack of participation was due to death 17 (7.1%), lost to follow-up 32 (13.4%) and refusal 18 (9.5%). Of the 171 patients, the median CD4 count at the time of ART initiation was 153 cells/µl [Interquartile range (IQR): 78 – 199], 164 (95.9%) had increased their CD4 cells count, with 74.3% having an increase of more than 150 cells/µl. Only 8 (4.7%) patients had a decline of CD4 cell count. The median CD4 cells count after a 2-year follow up was significantly higher (396 [IQR: 295 – 567]) than at baseline (153 [IQR: 78 – 199]) cells/ul; p-value &lt;0.0001). Conclusion: The CD4 cells count increased significantly after a follow up period of 2 years after ART use in this cohort. Early diagnosis and ART initiation could therefore improve outcomes in HIV-infected patients in resource limited settings.