Start Of Antiretroviral Therapy Research Articles

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch.

Why are HIV-infected people not started on antiretroviral therapy? A mixed-methods study from Gujarat, India.

Setting: Five purposively selected antiretroviral therapy (ART) centres in Gujarat, India. Objectives: To assess the proportion of ART-eligible people living with the human immunodeficiency virus (PLHIV) who were not initiated on ART within 2 months of being recorded as eligible, to identify factors associated with non-initiation and to explore reasons from the provider's perspective. Design: We used a mixed-methods design (triangulation) of 1) a quantitative phase involving record reviews and cohort analysis (Poisson regression) of PLHIV registered during April 2014-March 2015, and 2) a qualitative phase involving one-to-one interviews with 25 providers. Results: Of 2079 ART-eligible PLHIV, 339 (16%) were not started on ART within 2 months. PLHIV with CD4 counts of <350 cells/μl and patients who were labourers, hospitalised, bedridden or registered with certain ART centres were more likely not to be initiated on ART. Qualitative results were categorised into two broad themes: government health system- and patient-related challenges, which validated and complemented the quantitative findings. Conclusion: Several patient subgroups at greater risk of ART non-initiation were identified, along with reasons for risk; this has important programme implications for achieving the UNAIDS 90-90-90 goal, and particularly the second 90 component of having 90% of diagnosed PLHIV start ART.

Analisis Kecenderungan Survival Penderita HIV (+) dengan Terapi ARV Menggunakan Aplikasi Life Table

Survival analysis was a technique in statistical that used to analyze the data of an event, starting from the beginning to the end of the event and noted the timing of the events that have been determined, time was recorded in a day, week, month, or year. The purpose of this research was analyzed tendency survival with HIV positive of stage III to clinical stage AIDS. This research method used analytic observational with retrospective cohort design, analysis data used descriptive analysis and analysis of life table survival. The research used units of data population with inclution criteria, the first diagnosed with HIV (+) stage III at Dr. Kariadi Semarang Hospital from year 2008–2012, CD4 less from 200 sel/mm3 and consumed antiretroviral. The results showed a tendency survival of patients with HIV faster have been AIDS are low educational status 10 months, faster than on the status of higher education with decreased survival of 50%; the age group over 40 years, faster of 35 months less than the age group less 40, with years with decreased survival of 25%; HIV patients who started antiretroviral therapy with low CD4 counts, faster 7.5 months had been AIDS at the start of antiretroviral therapy with CD4 high, the chances of survival decrease by 60%. Early detection of HIV must be done in order to support the prevention of AIDS.

Same-Day ART Start for HIV

Antiretroviral therapy (ART) for people with newly diagnosed HIV infection is often delayed until lab test results are available and extensive

Cross-sectional comparative study of risky sexual behaviours among HIV-infected persons initiated and waiting to start antiretroviral therapy in rural Rakai, Uganda

ObjectivesTo compare risky sexual behaviours between HIV-positive persons initiated on antiretroviral therapy (ART) (ART-experienced) and persons waiting to start on ART (ART-naive) and assess predictors of risky sexual behaviours among...

Program Implementation of Option B+ at a President's Emergency Plan for AIDS Relief-Supported HIV Clinic Improves Clinical Indicators But Not Retention in Care in Mbarara, Uganda.

2013 WHO guidelines for prevention of mother to child transmission recommend combination antiretroviral therapy (ART) for all pregnant women, regardless of CD4 count (Option B/B+). We conducted a retrospective analysis of data from a government-operated HIV clinic in Mbarara, Uganda before and after implementation of Option B+ to assess the impact on retention in care. We limited our analysis to women not on ART at the time of their first reported pregnancy with CD4 count >350. We fit regression models to estimate relationships between calendar period (Option A vs. Option B+) and the primary outcome of interest, retention in care. One thousand and sixty-two women were included in the analysis. Women were more likely to start ART within 6 months of pregnancy in the Option B+ period (68% vs. 7%, p < 0.0001) and had significantly greater increases in CD4 count 1 year after pregnancy (+172 vs. -5 cells, p < 0.001). However, there was no difference in the proportion of women retained in care 1 year after pregnancy (73% vs. 70%, p = 0.34). In models adjusted for age, distance to clinic, marital status, and CD4 count, Option B+ was associated with a nonsignificant 30% increased odds of retention in care at 1 year [adjusted odds ratio (AOR) = 1.30, 95% CI 0.98-1.73, p = 0.06]. After transition to an Option B+ program, pregnant women with CD4 count >350 were more likely to initiate combination therapy; however, interventions to mitigate losses from HIV care during pregnancy are needed to improve the health of women, children, and families.

THE INFLUENCE OF HIV INFECTION DURATION BEFORE ANTIRETROVIRAL THERAPY ON IMMUNOLOGICAL TREATMENT FAILURE.

Some patients with HIV infection receiving virologically effective antiretroviral therapy (ART) did not show any growth in CD4 cell count during treatment. Despite the long-term treatment of patients, immunodeficiency persisted. In the observational cohort retro/prospective study we investigated the effect of the duration of HIV infection before starting the antiretroviral therapy on the development of immunological treatment failure. In a group of 140 HIV-infected patients a moderate inverse correlation was found between the duration of HIV infection and CD4 cell gain after 6 months, 1, 2 and 3 years of ART (r = -0.33, p < 0.01; r = -0.3, p < 0.01; r = -0.3, p < 0.01; r = -0.29, p < 0.01, respectively). In the case of ART starting at CD4 count of 200-350 cells/mcl statistically significant differences were revealed in the levels of relative CD4 count at 6 months, 1, 2 and 3 years of ART in sub-groups with durations of HIV infection prior to initiating therapy of 1-8 years and > 8 years (p = 0.035; p = 0.015; p = 0.05; p = 0.05, respectively). In patients who started ART with CD4 levels > 200 cells/mcl after 8 years of HIV infection, the risk of immunological treatment failure is 4 times higher as compared to patients with the same CD4 level, but lesser duration of HIV infection. The shorter the duration of HIV infection, the greater the increase in CD4 cell count. When starting ART at CD4 level of 200-350 cells/mcl, restoration of CD4 count is more intense in the group with lesser period of HIV infection. A negative effect of the >8-year infection duration before the start of ART on the development of the immunological treatment failure was observed in a subgroup with a starting level of CD4 > 200 cells /mcl.

HIV and hepatitis C treatment uptake among people who use drugs participating in the Amsterdam Cohort Studies, 1985–2015

BackgroundHIV-positive people who use drugs (PWUD) start antiretroviral therapy (ART) later than other risk groups, and among HCV-positive PWUD, HCV treatment uptake is low. Nowadays, HCV direct-acting antivirals (DAAs) are available and reimbursed in the Netherlands (since 2014). The Amsterdam Cohort Studies (ACS), initiated in 1985, provides us the opportunity to describe temporal trends in ART and HCV-treatment uptake among PWUD through 2015. MethodsWe analyzed data from PWUD participating in the ACS between 1985 and 2015. ART and HCV-treatment data were obtained from ACS questionnaires and medical records. Treatment uptake was defined by: treatment initiation (the proportion initiating any kind of ART/HCV treatment when treatment-naïve) and coverage (the proportion ever treated for HIV/HCV) among all HIV-/HCV-RNA-positive PWUD. Each was calculated per calendar year. We estimated the cumulative probability of ART uptake in the pre-cART (<1996) and cART era (January 1, 1996) among HIV seroconverters, with all-cause mortality as a competing risk. ResultsOf 1305 PWUD, 263 (20.2%) were HIV-antibody positive and 810 (62.1%) were HCV-antibody positive, at study entry. ART coverage increased over time, from 5.7% in 1990 and 42.2% in 1996 to 91.7% in 2015. The proportion initiating ART ranged from 4.8% in 1990 to 33.3% in 2011. At 8 years after HIV seroconversion, cumulative probability of ART uptake was 42.5% in the pre-cART era and 61.5% in the cART era. HCV treatment initiation peaked in 2006 (9.7%). HCV-treatment coverage was 43.9% in 2015 but lower among HIV-coinfected (23.5%) than HCV-monoinfected PWUD (52.5%). In 2015, 3.0% initiated HCV treatment with DAAs. ConclusionWe observed an increase in ART and HCV-treatment coverage among PWUD over time. As expected, ART uptake was higher in the cART era than the pre-cART era. Although in 2015 HCV treatment coverage was relatively high, DAA uptake was still low.

Should We Be Testing for Baseline Integrase Resistance in Patients Newly Diagnosed With Human Immunodeficiency Virus?

Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR testing"), although this class of drugs is a component of most recommended first-line regimens. We compared the 96-week clinical outcomes and cost-effectiveness of 2 strategies: no IR testing vs IR testing performed at human immunodeficiency virus (HIV) diagnosis. The base case prevalence of transmitted integrase strand transfer inhibitor (INSTI)-resistant (INSTI-R) virus is estimated at 0.1%. With no IR testing, all patients start dolutegravir (DTG)-based ART after genotype; 12-week suppression rates are 90% (INSTI-susceptible [INSTI-S] virus) and 35% (INSTI-R virus). Those not suppressed at 12 weeks undergo IR testing; if diagnosed with INSTI-R virus, they change to ritonavir-boosted darunavir (DRV/r)-based ART. With IR testing, all patients are diagnosed with INSTI-S/INSTI-R virus prior to ART initiation and start DTG- or DRV/r-based regimens, respectively. Costs include IR tests (175 US dollars [USD]) and ART (41100-44900 USD/year). We examined the impact of key parameters in sensitivity analyses. IR testing resulted in worse clinical outcomes compared to no IR testing and increased costs by 200 USD/person/year. Prevalence of transmitted INSTI-R virus did not affect the favored strategy. No IR testing remained clinically preferred unless DTG suppression of INSTI-R virus was <20% or 96-week DRV/r suppression was >92%. If quality of life was worse with DRV/r- than DTG-based ART, no IR testing was clinically preferred over an even broader range of parameters. In patients with newly diagnosed HIV, IR testing is projected to result in worse outcomes and is not cost-effective. Pretreatment assessment for INSTI resistance should not be recommended in treatment guidelines.

Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies

SummaryBackgroundHealth care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013.MethodsWe analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART.Findings88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men.InterpretationEven in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements.FundingUK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.

Improved life expectancy of people living with HIV: who is left behind?

Improved life expectancy of people living with HIV: who is left behind?

Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study

SummaryBackgroundThe length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.MethodsThe UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline.ResultsOf the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6–8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations.InterpretationA substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development.FundingUK Medical Research Council.

Migrant women living with HIV in Europe: are they facing inequalities in the prevention of mother-to-child-transmission of HIV?: The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.

In pregnancy early interventions are recommended for prevention of mother-to-child-transmission (PMTCT) of HIV. We examined whether pregnant women who live with HIV in Europe and are migrants encounter barriers in accessing HIV testing and care. Four cohorts within the European Pregnancy and Paediatric HIV Cohort Collaboration provided data for pooled analysis of 11 795 pregnant women who delivered in 2002-12 across ten European countries. We defined a migrant as a woman delivering in a country different from her country of birth and grouped the countries into seven world regions. We compared three suboptimal PMTCT interventions (HIV diagnosis in late pregnancy in women undiagnosed at conception, late anti-retroviral therapy (ART) start in women diagnosed but untreated at conception and detectable viral load (VL) at delivery in women on antenatal ART) in native and migrant women using multivariable logistic regression models. Data included 9421 (79.9%) migrant women, mainly from sub-Saharan Africa (SSA); 4134 migrant women were diagnosed in the current pregnancy, often (48.6%) presenting with CD4 count <350 cells/µl. Being a migrant was associated with HIV diagnosis in late pregnancy [OR for SSA vs. native women, 2.12 (95% CI 1.67, 2.69)] but not with late ART start if diagnosed but not on ART at conception, or with detectable VL at delivery once on ART. Migrant women were more likely to be diagnosed in late pregnancy but once on ART virological response was good. Good access to antenatal care enables the implementation of PMTCT protocols and optimises both maternal and children health outcomes generally.

Efavirenz-based simplification after successful early lopinavir-boosted-ritonavir-based therapy in HIV-infected children in Burkina Faso and C\xf4te d\u2019Ivoire: the MONOD ANRS 12206 non-inferiority randomised trial

BackgroundThe 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years.MethodsThe MONOD ANRS 12026 study is a phase 3 non-inferiority open-label randomised clinical trial conducted in Abidjan, Côte d’Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 12–15 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test).ResultsBetween May 2011 and January 2013, 156 children (median age 13.7 months) were initiated on ART. After 12–15 months on ART, 106 (68%) were randomised to one of the two treatment arms (54 LPV, 52 EFV); 97 (91%) were aged <3 years. At 12 months post-randomisation, 46 children (85.2%) from LPV versus 43 (82.7%) from EFV showed virological suppression (defined as a VL <500 copies/mL; difference, 2.5%; 95% confidence interval (CI), −11.5 to 16.5), whereas seven (13%) in LPV and seven (13.5%) in EFV were classed as having virological failure (secondary outcome, defined as a VL ≥1000 copies/mL; difference, 0.5%; 95% CI, −13.4 to 12.4). No significant differences in adverse events were observed, with two adverse events in LPV (3.7%) versus four (7.7%) in EFV (p = 0.43). On genotyping, 13 out of 14 children with virological failure (six out of seven EFV, seven out of seven LPV) had a drug-resistance mutation: nine (five out of six EFV, four out of seven LPV) had one or more major NNRTI-resistance mutations whereas none had an LPV/r-resistance mutation.ConclusionsAt the VL threshold of 500 copies/mL, we could not conclusively demonstrate the non-inferiority of EFV on viral suppression compared to LPV because of low statistical power. However, non-inferiority was confirmed for a VL threshold of <1000 copies/mL. Resistance analyses highlighted a high frequency of NNRTI-resistance mutations. A switch to an EFV-based regimen as a simplification strategy around the age of 3 years needs to be closely monitored.Trial registrationClinicalTrial.gov registry n°NCT01127204, 19 May 2010.

The potential impact and cost of focusing HIV prevention on young women and men: A modeling analysis in western Kenya.

ObjectiveWe compared the impact and costs of HIV prevention strategies focusing on youth (15–24 year-old persons) versus on adults (15+ year-old persons), in a high-HIV burden context of a large generalized epidemic.DesignCompartmental age-structured mathematical model of HIV transmission in Nyanza, Kenya.InterventionsThe interventions focused on youth were high coverage HIV testing (80% of youth), treatment at diagnosis (TasP, i.e., immediate start of antiretroviral therapy [ART]) and 10% increased condom usage for HIV-positive diagnosed youth, male circumcision for HIV-negative young men, pre-exposure prophylaxis (PrEP) for high-risk HIV-negative females (ages 20–24 years), and cash transfer for in-school HIV-negative girls (ages 15–19 years). Permutations of these were compared to adult-focused HIV testing coverage with condoms and TasP.ResultsThe youth-focused strategy with ART treatment at diagnosis and condom use without adding interventions for HIV-negative youth performed better than the adult-focused strategy with adult testing reaching 50–60% coverage and TasP/condoms. Over the long term, the youth-focused strategy approached the performance of 70% adult testing and TasP/condoms. When high coverage male circumcision also is added to the youth-focused strategy, the combined intervention outperformed the adult-focused strategy with 70% testing, for at least 35 years by averting 94,000 more infections, averting 5.0 million more disability-adjusted life years (DALYs), and saving US$46.0 million over this period. The addition of prevention interventions beyond circumcision to the youth-focused strategy would be more beneficial if HIV care costs are high, or when program delivery costs are relatively high for programs encompassing HIV testing coverage exceeding 70%, TasP and condoms to HIV-infected adults compared to combination prevention programs among youth.ConclusionFor at least the next three decades, focusing in high burden settings on high coverage HIV testing, ART treatment upon diagnosis, condoms and male circumcision among youth may outperform adult-focused ART treatment upon diagnosis programs, unless the adult testing coverage in these programs reaches very high levels (>70% of all adults reached) at similar program costs. Our results indicate the potential importance of age-targeting for HIV prevention in the current era of ‘test and start, ending AIDS’ goals to ameliorate the HIV epidemic globally.

Neuropsychiatric manifestations in patients with HIV treated with antiretroviral drugs versus untreated

IntroductionUntreated patients for H.I.V can present various types of neuropsychiatric syndromes (NPS): subclinical cognitive symptoms, behavioral changes, agitation, personality changes, dementia complex associated with H.I.V and delirium, depressive disorder, bipolar affective disorder or manic episode. However, it is controversial whether antiretroviral induce NPS, or on the contrary, when there are patients will evolve into an AIDS stage for therapeutic resistance or noncompliance.AimsDescribe qualitatively and quantify the epidemiological point of the main subclinical and NPS symptoms in patients untreated and treated with antiretroviral drugs and their frequencies. Propose pharmacological treatments for each of the specified conditions.MethodsSearch in PubMed with the words “Neuropsychiatric and antiretroviral therapy” by applying the limits: full and free texts, past 10 years, Human, English language and adults; research liaison psychiatry textbooks.ResultsResults yielded 381 articles with the criteria selecting 102, the most relevant for the purposes of work. They chose four most relevant chapters in the literature.ConclusionsThe most effective treatment of NPS in unmedicated patients is to start antiretroviral therapy; only if it does not improve them should be introduced psychiatric drugs as if they were functional. 50% of treated with efavirenz patients will develop NPS in the early days with gradual decrease. The dropout rate associated with these adverse events varies from 2.6–16%. Treatment of these NPS a challenge by the existence of numerous drug interactions, it is essential to know to deal with these entities to improve the quality of life of people with this chronic disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Clinico-Social and Immunological Profile of Antiretroviral Naïve Children Living With HIV In Tertiary Care Hospital, Delhi

Introduction: This study was undertaken to assess the clinical profile of children living with HIV at the time of their enrolment in an ART centre in Delhi. The study also attempts to understand association between clinical staging and immunological profile (CD4 count/percentage) in HIV infected children. The findings of this study may help policy makers to plan better health care of CLHIV in resource constrained country like India. The Objectives of the study were to assess the baseline clinico-social and immunological profile of HIV positive children before the start of Antiretroviral Therapy, to study clinicosocial and morbidity profile of HIV positive children at the time of their enrolment in ART centre and to study the association between immunodeficiency and clinical staging of CLHIV.Methodology: The present study, conducted between December 2012 and March 2013, is a retrospective case review of 83 antiretroviral naïve Children living with HIV aged 8 months to 13 years and attending paediatric ART clinic of a tertiary care hospital of Delhi. After the infection was established on serological grounds, information on socio-demographic, clinical and immunological profile was studied.Results: Majority (62.7%) of CLHIV were boys. Both parents of CLHIV were found to be positive in 63.9% while mother was found to be positive in 69.9%. The most common route of HIV infection was mother-to-child transmission (69.9%), followed by transmission though blood/blood products (12.0%). Every three out of four children (71.1%) were in WHO clinical stage III or IV. Three out of four (74.7%) children presented with fever, one in two with cough (56.6%). Diarrhoea (56.6%), pneumonia (41.0%), popular pruritic eruptions (18.1%), candidiasis (16.9%) and tuberculosis (14.5%) were the most common opportunistic infections in these children. The most common signs present were hepatomegaly (81.9%), anaemia (78.3%) and lymphadenopathy (72.3%).Conclusion: Mother to child transmission is the most common route of transmission in CLHIV. At enrolment more than half of the children were in clinical stage III&amp;IV. Fever, cough, diarrhoea, weight loss, rashes were common morbidities of the children. Majority of the children had hepatomegaly, anaemia and lymphadenopathy.SAARC J TUBER LUNG DIS HIV/AIDS, 2016; XIII(1) p.32-38

Survival Estimates and Mortality Risk Factors in a Cohort of HIV Vertically Infected Individuals in Salvador, Brazil.

There are few data on long-term survival of Brazilian children with vertically acquired HIV infection. We assessed survival, mortality risk factors and response to antiretroviral therapy (ART). We compared children with early and late access to care. We used Kaplan-Meier survival curves with Log-rank tests to compare survival time and mortality rates of 245 HIV vertically infected children admitted for care during 2002-2014. Total follow-up sum was 1584.4 person-years. Overall survival was 83.9%. Median age at start of ART was 51.6 (18.0-94.2) months, and median age at death was 8.2 (1.7-10.1) years (mortality rate: 1.7/100 person-years). Pneumonia and sepsis were the main causes of death. Male gender, viral load (VL) ≥100,000 copies, severe immunosuppression, moderate/severe symptoms and history of opportunistic infection were associated with higher mortality in bivariate analysis. Only severe symptoms remained associated in multivariate analysis (P = 0.03). There was no difference in mortality in early compared to late access group. Overall, 217 patients received ART; 192 had a recent VL, of which 116 (59.8%) had ≤400 copies. Variables associated with therapeutic failure were as follows: VL ≥100,000 copies, less immune suppression, age <12 months at admission and age <3 years at ART start. We have a high mortality rate in comparison with developed countries. Although early access did not impact mortality, we detected a trend in favor of early treatment as a protecting factor against mortality. We need to increase adherence to care and treatment, and better drugs to optimize outcomes.

Acceptability of Early Antiretroviral Therapy Among South African Women.

WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22-30), in a 10year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was217 cells/µl (range 135-372) before 2010, and increased to531 cells/µl (range 272-1095) by 2015 (p<0.001). Median viral load at ART initiation decreased over this period from 5.2 (IQR 4.6-5.6) to 4.1 (IQR 3.4-4.6) log copies/ml (p=0.004). Virological suppression rates at 3, 6, 12 and 18months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24-33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.

HIV-1 persistent viremia is frequently followed by episodes of low-level viremia

After the start of antiretroviral therapy (ART), plasma HIV-RNA levels should fall below the limit of detection (LOD) within 24 weeks. Hence, the prolonged decline of HIV-RNA after ART initiation is defined as persistent viremia (PV). In this retrospective study, we analyzed factors associated with PV. Next-generation sequencing of viral RNA/DNA was performed to study viral evolution and the emergence of drug-resistance mutations in HIV-infected patients with PV (n = 20). In addition, HIV-DNA species, immunological parameters, and clinical data of the patients were analyzed. We found that the possible causes for PV were divers, and both virologic and host parameters of this particular cohort were heterogeneous. We identified viruses with therapy-associated DRMs in six patients (30%); two of these were detected as minority variants. Five patients had sub-optimal drug levels (25%) and the baseline plasma viral loads were relatively high. Strikingly, we observed that >40% of the PV patients finally reaching HIV levels below the LOD later on showed up with episodes of low-level viremia (LLV). However, the amount of PBMC derived HIV-DNA species was not correlated with the likelihood of LLV after PV. According to our data, we conclude that drug-resistant viruses, sub-optimal drug level, and high baseline viral loads might be probable reasons for the prolonged RNA decline only in a sub-set of patients. In the absence of emerging DRMs and/or compliance issues, the clinical implications of PV remain unclear; however, PV appears to be a risk factor for episodes of LLV.