Costs and benefits of secrecy: the dilemma experienced by adolescents seropositive for HIV.

This study explored the experiences of the first generation of adolescents who acquired HIV through vertical transmission when disclosing their diagnosis to friends and romantic partners. The study sample was selected by convenience, with 20 patients (13-20 years old) participating in a qualitative investigation using individual interviews (language: Portuguese; duration: 45 minutes). The participants were followed in specialized clinics for the treatment of pediatric AIDS in São Paulo, Brazil. The results suggest that families who live with HIV tend to keep it a secret, and such behavior is learned and accepted unquestioningly as natural. Respect for privacy and the fear of rejection, coupled with the belief that information about their disease will be spread, are the main beliefs with which participants justify their secrecy. In terms of romantic relationships, adolescents were aware that their HIV status should at some point be shared with current or future sexual partners. However, the decision to reveal an HIV diagnosis in romantic relationships is permeated by anxieties, uncertainties about the right time, and fear of abandonment. In any case, telling the truth requires trust, guarantees of the other's love, and, in some cases, probing romantic partners beforehand to learn their perceptions about the disease. Participants who had experiences disclosing their HIV status shared positive and negative results, including emotional support, acceptance, and understanding, along with ostracism, discrimination, and abandonment by family members. The findings of this paper reinforce the challenges of revealing an HIV diagnosis to third parties. It requires understanding the meaning and importance of the secret for each patient, along with the conflict between the right to confidentiality and the responsibility of treating others exposed to the disease. All these aspects should be discussed extensively with this population and incorporated into clinical practice.

Renal abnormalities in a cohort of HIV-infected children and adolescents.

BACKGROUND: This study aimed to identify the prevalence of renal abnormalities and the evolution of glomerular filtration rate (GFR) among human immunodeficiency virus (HIV)- infected children and adolescents followed up in an infectious disease outpatient pediatric clinic. METHODS: We performed a cohort study of 115 children and adolescents. Outcomes of two evaluations for urinalysis, microalbuminuria/urinary creatinine ratio, urinary retinol-binding protein (uRBP) concentration, and estimated GFR (eGFR) were obtained for each patient, with an average interval of 6 months between evaluations. These changes were correlated with gender, age, race, body mass index (BMI), height-for-age (H/A) percentile, clinical and immunological classification of HIV infection, use of antiretroviral therapy (ART), HIV viral load (VL), and CD4+ T-lymphocyte count. RESULTS: Mean patient age at the time of inclusion in the study was 12.6 ± 3.2 years; 50.4 % were male, 81.7 % had acquired immune defeciency syndrome (AIDS), 80.9 % had CD4+ < 500 cells/mm(3), and 87.8 % were on ART. Urinary changes included hematuria (11.3 %), proteinuria (7 %), and microalbuminuria (11.6 %); uRBP was present in 3.8 %; and mean eGFR was 163 ± 32 ml/min/1.73 m(2). CONCLUSIONS: The subclinical renal abnormalities found in this study may indicate early manifestations of a broad spectrum of renal dysfunction associated with HIV and involves the decision to initiate or modify ART.

Transition to dolutegravir-based ART in 35 low- and middle-income countries: a global survey of HIV care clinics.

OBJECTIVE: We studied the transition to dolutegravir-containing antiretroviral therapy (ART) at HIV treatment clinics within the International epidemiology Databases to Evaluate AIDS (IeDEA). DESIGN: Site-level survey conducted in 2020-2021 among HIV clinics in low- and middle-income countries (LMICs). METHODS: We assessed the status of dolutegravir rollout and viral load and drug resistance testing practices for patients on ART switching to dolutegravir-based regimens. We used generalized estimating equations to assess associations between clinic rollout of both first- and second-line dolutegravir-based ART regimens (dual rollout) and site-level factors. RESULTS: Of 179 surveyed clinics, 175 (98%) participated; 137 (78%) from Africa, 30 (17%) from the Asia-Pacific, and 8 (5%) from Latin America. Most clinics (80%) were in low- or lower-middle-income countries, and there were a mix of primary-, secondary- and tertiary-level clinics. Ninety percent reported rollout of first-line dolutegravir, 59% of second-line, 94% of first- or second-line and 55% of dual rollout. The adjusted odds of dual rollout were higher among tertiary-level (aOR 4.00; 95% CI 1.39 to 11.47) and secondary-level clinics (aOR 3.66; 95% CI 2.19 to 6.11) than in primary-level clinics. Over half (59%) of clinics that introduced first- or second-line dolutegravir-based ART required recent viral load testing before switching to dolutegravir, and 15% performed genotypic resistance testing at switch. CONCLUSIONS: Dolutegravir-based ART was rolled out at nearly all IeDEA clinics in LMICs, yet many switched patients to dolutegravir without recent viral load testing and drug resistance testing was rarely performed. Without such testing, drug resistance among patient switching to dolutegravir may go undetected.

Lessons learned from over a decade of data audits in international observational HIV cohorts in Latin America and East Africa.

Introduction: Routine patient care data are increasingly used for biomedical research, but such "secondary use" data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.

Human polyomaviruses JC and BK in the urine of Brazilian children and adolescents vertically infected by HIV.

The aim of this study was to characterize the urinary excretion of the BK (BKV) and JC (JCV) human polyomaviruses in a cohort of human immunodeficiency virus (HIV)-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y); range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y). Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4% and 40.4%, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6% and 54.3% of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5% of subjects and for BKV in 12.5% of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001). In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001) and a trend of lower JCV excretion (p = 0.07). One patient in Group I (1/116, 0.9%) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.

Assessment of liver disease by non-invasive methods in perinatally infected Brazilian adolescents and young adults living with Human Immunodeficiency Virus (HIV).

INTRODUCTION: Effective and long-term combined antiretroviral therapy (cART) has decreased morbidity and mortality in HIV-infected individuals. Despite treatment advances, HIV-infected children continue to develop noninfectious conditions, including liver fibrosis. METHODS: Cross-sectional study designed to identify liver fibrosis in HIV-infected adolescents and young adults, in an outpatients clinic of Pediatric Infectious Diseases Division at Escola Paulista de Medicina/Universidade Federal de São Paulo (UNIFESP), diagnosed by noninvasive methods (liver elastography-FibroScan®, APRI and FIB4). Variables examined included demographics, clinical, laboratories, HIV treatment. All participants underwent FibroScan® to measure liver parenchyma elasticity. Values equal to above 7.0 kPa were interpreted as the presence of significant liver fibrosis. Two different biomarkers of liver fibrosis were employed: the AST-to-Platelet Ratio Index (APRI) and the Fibrosis-4 score (FIB-4). APRI values above 1.5 have been considered as levels of clinically significant liver fibrosis and FIB-4 values above 3.25 suggested the presence of advanced fibrosis. RESULTS: Between August 2014 and March 2017, the study enrolled 97 patients, age 10-27 years old, fourteen of 97 subjects (14.4%) presented liver stiffness (≥7 kPa) detected by the liver elastography. No patient had APRI> 1.5. No patient had FIB4 value > 3.25. The only isolated laboratory parameter that could be significantly associated with high liver stiffness was thrombocytopenia (p = 0.022, Fisher's exact test). CONCLUSION: Liver stiffness was identified in 14.4% (14/97) of this cohort by liver elastography. Liver disease in HIV-infected adolescents and young adults manifests itself silently, so should be routinely investigated.

Clinical and Laboratory Characteristics of Herpes Zoster in Patients With HIV/AIDS and Those With Juvenile Systemic Lupus Erythematosus.

BACKGROUND: HIV infection and juvenile systemic lupus erythematosus (jSLE) are risk factors for the development of herpes zoster (HZ) and its complications. Both diseases share similar immunologic aspects, such as immunodeficiency and immune activation. Therefore, our objective was to evaluate and compare the frequency and characteristics of HZ episodes in pediatric patients with HIV infection and jSLE. METHODS: A retrospective cohort study was carried out with the evaluation of 2 pediatric cohorts: HIV patients who were followed from January 1987 to December 2014 and patients with jSLE followed up from January 1990 to December 2014 in outpatient clinics. RESULTS: Of the 190 HIV patients, 48 had HZ (25.3%), with 67 episodes; of the 92 patients with jSLE, 27 had HZ (29.3%), totaling 28 episodes. The median age at the first episode of HZ was higher in the jSLE than in the HIV group (8.9 vs. 12.5 years, respectively) (P = 0.020). HIV patients were more likely to have recurrent HZ (P = 0.025). In addition, there was a tendency for HIV patients to present with disseminated HZ more frequently (P = 0.060). Although the hospitalization rate was similar between groups, patients with jSLE received intravenous acyclovir more frequently (P = 0.014). When HIV non-immune reconstitution syndrome patients were compared with jSLE group, recurrence of HZ in HIV was the only significant difference between groups (P = 0.017). CONCLUSIONS: Patients with HIV had more recurrent HZ than patients with jSLE.

Chronic meningococcemia in a vertically HIV-infected adolescent.

Chronic meningococcemia is a rare manifestation of meningococcal disease, characterized by a period of more than one week of intermittent or continuous fever, arthralgia and skin lesions without meningitis. It can occur both in previously healthy and immunocompromised patients. The gold standard for the diagnosis is culture isolation of Neisseria meningitidis in sterile material. We describe a case of a vertically HIV-infected adolescent with chronic meningococcal disease.

Self-audits as alternatives to travel-audits for improving data quality in the Caribbean, Central and South America network for HIV epidemiology.

INTRODUCTION: Audits play a critical role in maintaining the integrity of observational cohort data. While previous work has validated the audit process, sending trained auditors to sites ("travel-audits") can be costly. We investigate the efficacy of training sites to conduct "self-audits." METHODS: In 2017, eight research groups in the Caribbean, Central, and South America network for HIV Epidemiology each audited a subset of their patient records randomly selected by the data coordinating center at Vanderbilt. Designated investigators at each site compared abstracted research data to the original clinical source documents and captured audit findings electronically. Additionally, two Vanderbilt investigators performed on-site travel-audits at three randomly selected sites (one adult and two pediatric) in late summer 2017. RESULTS: Self- and travel-auditors, respectively, reported that 93% and 92% of 8919 data entries, captured across 28 unique clinical variables on 65 patients, were entered correctly. Across all entries, 8409 (94%) received the same assessment from self- and travel-auditors (7988 correct and 421 incorrect). Of 421 entries mutually assessed as "incorrect," 304 (82%) were corrected by both self- and travel-auditors and 250 of these (72%) received the same corrections. Reason for changing antiretroviral therapy (ART) regimen, ART end date, viral load value, CD4%, and HIV diagnosis date had the most mismatched corrections. CONCLUSIONS: With similar overall error rates, findings suggest that data audits conducted by trained local investigators could provide an alternative to on-site audits by external auditors to ensure continued data quality. However, discrepancies observed between corrections illustrate challenges in determining correct values even with audits.

Prolonged Antiretroviral Therapy in Adolescents With Vertical HIV Infection Leads to Different Cytokine Profiles Depending on Viremia Persistence.

BACKGROUND: We investigated immune activation, exhaustion markers and cytokine expression upon stimulation in adolescents with vertical HIV infection. METHODS: Thirty adolescents receiving antiretroviral therapy (ART) for vertical HIV infection, including 12 with detectable viral load (HIV/DET), 18 with undetectable viral load (HIV/UND) and 30 control adolescents without HIV infection (CONTROL), were evaluated for immune activation and programmed cell death protein-1 expression by flow cytometry, and 21 cytokines by Luminex Multiple Analyte Profiling technology after in vitro peripheral blood phytohemagglutinin stimulation. RESULTS: Lower CD4 T cells and higher T cell activation and exhaustion markers were noted on CD4 T and on CD8 T cells and memory subsets from HIV/DET group, who also produced lower in vitro IFN-gamma, IL-10, IL-13, IL-17A, IL-5 and IL-6 than HIV/UND group. HIV/UND were comparable with CONTROL group in respect to CD4 T cell counts and T cell activation and exhaustion markers, but with higher in vitro production of ITAC (a chemokine with leukocyte recruitment function), IL-4 and IL-23. An inverse correlation between cytokine production and programmed cell death protein-1 expression on CD4 T and CD8 T subsets was detected. CONCLUSIONS: Persistent viremia despite ART leads to T cell activation and immune exhaustion with low cytokine production, whereas viral suppression by ART leads to parameters similar to CONTROL, although a different cytokine profile is observed, indicating residual HIV impact despite absence of detectable viremia.

Validity and reliability of a self-efficacy expectancy scale for adherence to antiretroviral therapy for parents and carers of children and adolescents with HIV/AIDS.

OBJECTIVE: To validate and evaluate the reproducibility of a self-efficacy (SE) scale for adherence to antiretroviral therapy in children and adolescents with HIV/AIDS, taking into account the perspective of parents/guardians. METHODS: The study was carried out at the Hospital-Dia, Centro de Referência e Treinamento em DST/AIDS (CRT/SP), in São Paulo, Brazil. The parents/guardians of 54 children and adolescents aged 6 months to 20 years were interviewed during routine consultations at our service. Data on SE were collected using the Self-Efficacy for Following Anti-Retroviral Prescription Scale, and SE scores were calculated in two different ways: factor analysis and a predefined formula. The scale's internal consistency was verified using Cronbach's alpha coefficient. Validity was tested by comparing the mean scores of a group of patients who did adhere to antiretroviral treatment with those of a group that did not (Mann-Whitney test) and by calculating the Spearman correlation coefficient for agreement between scores and clinical parameters. Reproducibility was verified using the Wilcoxon test, intraclass correlation coefficients (r(icc)) and Bland-Altman plots. RESULTS: The SE scale demonstrated good internal consistency (alpha = 0.87) and good reproducibility (r(icc) = 0.69 and r(icc) = 0.75). In terms of validity, the SE scale was capable of differentiating adherent patients from those who did not adhere to their antiretroviral treatment (p = 0.002) and exhibited a significant correlation with CD4 counts (r = 0.28; p = 0.04). CONCLUSIONS: The SE scale can be used to assess adherence to antiretroviral therapy in children and adolescents with HIV/AIDS, taking into account the perspective of parents/carers.

Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission.

BACKGROUND: Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. METHODOLOGY: Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. RESULTS: A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. CONCLUSION: HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT. TRIAL REGISTRATION: NCT00099359.

Congenital Cytomegalovirus and HIV Perinatal Transmission.

BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy. METHODS: cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time polymerase chain reaction. RESULTS: Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: < 200-2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (P < 0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intrapartum HIV infection (P < 0.0001). Rates of cCMV among HIV-infected infants were 4-fold greater (adjusted OR, 4.4; 95% CI: 2.3-8.2) and 6-fold greater among HIV in utero-infected infants (adjusted OR, 6; 95% CI: 3-12.1) compared with HIV-exposed, uninfected infants. cCMV was not associated with mode of delivery, gestational age, Apgar scores, 6-month infant mortality, maternal age, race/ethnicity, HIV viral load or CD4 count. Primary cCMV risk factors included infant HIV-infection, particularly in utero infection. CONCLUSION: High rates of cCMV with high urinary CMV VL were observed in HIV-exposed infants. In utero HIV infection appears to be a major risk factor for cCMV in infants whose mothers have not received combination antiretroviral therapy in pregnancy.

Maternal antiretrovirals and hepatic enzyme, hematologic abnormalities among human immunodeficiency virus type 1-uninfected infants: the NISDI perinatal study.

OBJECTIVES: To assess hepatic enzyme (HE) and hematologic abnormalities among human immunodeficiency virus-1-uninfected infants according to maternal antiretroviral regimen during pregnancy. STUDY DESIGN: In a prospective cohort, HE and hematologic values of human immunodeficiency virus-1-uninfected, term infants with hospital discharge (HD) within 6 days after birth were evaluated. Maternal antiretroviral regimens were categorized as: 1 or 2 nucleoside reverse transcription inhibitors (NRTIs), highly active antiretroviral therapy (HAART)/protease inhibitor (PI), or HAART/non-NRTI. RESULTS: Among 503 infants, 63% and 24% had HE and hemoglobin abnormalities, respectively, at HD. Most or all HE and hemoglobin abnormalities (96-100%) were grade 1 or 2. At HD, infants with maternal HAART/PI or HAART/non-NRTI were more likely to have elevated HE [adjusted odds ratio (AOR): 1.9, 2.4, respectively] compared with infants whose mothers received 1 or 2 NRTIs. Infants with maternal HAART/PI were less likely to have abnormal hemoglobin values at HD (AOR, 0.5) when compared with those whose mothers received 1 or 2 NRTIs. Persistently abnormal hemoglobin and HE values decreased with time, such that <10% of infants had abnormalities at 6 months of age. CONCLUSIONS: Maternal receipt of HAART regimens was associated with an increased risk of HE abnormalities, and maternal HAART/PI was associated with a lower risk of abnormal hemoglobin values, at HD. Abnormalities of HE and hemoglobin were generally mild and transient.

HIV-1-infected children on HAART: immunologic features of three different levels of viral suppression.

BACKGROUND: HIV-1-infected children show changes of blood lymphocyte subpopulations. We have, therefore, investigated how highly active anti-retroviral therapy (ART) alter these subsets. Blood samples were taken from 41 HIV-1-infected children on ART who were divided into groups showing good, partial and poor responses to ART on the basis of viral load (VL) measurement in blood. The observations were compared to those seen in 20 uninfected children. METHODS: The samples were studied using 4-color flow cytometry for "naïve", central memory and effector memory cells as well as for CD38 expression as the sign of activation within both the CD4+ and the CD8+ T cell populations. HIV-1 infected children were also evaluated for the presence and the titers of antibodies induced by vaccination against childhood infections in our patients while on HAART. RESULTS: Lymphocyte counts were lower in the "poor" viral load responding (VLR) group when compared with partial and good VLRs. Poor VLRs had lower total and naïve CD4+ T cell counts. HIV-1-infected children from all three groups had high CD8+ T cell counts. Central memory CD4+ and CD8+ T cell percentages were particularly low in the poor VLR group while in the poor VLR group the percentages of effector memory CD4+ and CD8+ T cells were higher when compared with the control group. Higher cellular activation of CD8+ T cells was observed in HIV-1-infected children, particularly when analyzed for the intensity of CD38 expression in the poor VLR group. CD5 expression on B cells was higher among all HIV-1-infected children. Antibodies to tetanus, diphtheria, measles, rubella, and hepatitis B were present in a large proportion of children but the titers were similarly low for all three groups of HIV-infected children. CONCLUSIONS: Children with different levels of viral response to HAART present immune phenotype characteristics that tend to place the children with partial and good virological responses into the same group. These children are still moderately deficient in their immune responses but show better recovery than seen with children in the poor VLR group. These observations indicate that the proportions of central memory cells among the CD4+ T cells and the intensity of the expression of CD38 activation antigen on CD8+ T cells provide more informative parameters for monitoring children on HAART than the absolute numbers of CD4+ and CD8+ T cells alone.

CCR5 genotypes and progression to HIV disease in perinatally infected children.

The CCR5 molecule, a chemokine receptor, is the most important co-receptor for macrophage-tropic HIV-1. A 32-bp deletion in the gene encoding CCR5 (CCR5-del32) confers nearly complete resistance to HIV-1 infection in homozygotes, and slows the rate of progression to AIDS in heterozygous adults. The aim of this study was to describe the CCR5 genotypes and the characteristics of HIV disease progression in perinatally infected children. From a total of 51 children analyzed for the CCR5-del32 mutation, 18 (35%) were considered to be rapid progressors, 28 (55%) were moderate progressors and 5 (10%) were slow progressors. A portion of the CCR5 gene was amplified by PCR from genomic DNA followed by agarose gel electrophoresis. Forty-nine children (96%) carried the homozygous wild type genotype for CCR5 while 2 (4%) carried the heterozygous wt/del32 genotype. In the population studied, the CCR5 genotype was unable to account for the differences in pattern of the disease progression among the three groups (rapid, moderate and slow progressors), and the allele frequency of CCR5-del32 was too low to allow statistical comparisons with adequate resolving power. Studies on larger populations may help to further elucidate the role of this allele and other host factors in the regulation of HIV-1 pathogenesis in children.

Factors associated with clinical, immunological and virological responses in protease-inhibitor-experienced Brazilian children receiving highly active antiretroviral therapy containing lopinavir-ritonavir.

This study evaluates clinical, virological and immunological responses to antiretroviral (ARV) therapy based on Lopinavir/ritonovir (LPV/r) in previously protease -inhibitor-experienced children. The study included 29 Brazilian children (median age = 5.91 years) who had failed previous ARV therapy and had begun a regimen based on LPV/r. At 12 months follow-up, a good virological response to LPV/r therapy was defined as achieving an undetectable viral load or as a decrease in plasma HIV RNA levels to > 1 log. A good immunological response was defined as an increase in CD4+ cell count from baseline sufficient to attain a better CDC immune stage classification. The number of infectious episodes 12 months before and 12 months after beginning LPV/r was assessed. Sixteen (55.2%) and 19 (65.5%) of 29 patients exhibited good virological and immunological responses, respectively. Baseline CD4+ values (>500) predicted both virological and immunological responses (p<0.05). Older children were less likely to develop an immunological response (p<0.001) than younger children. Nine children receiving 3 ARV drugs plus LPV/r showed an immunological response (100%) compared to 10/20 (50%) children receiving 2 drugs plus LPV/r (p=0.01). A lower number (n<5) of infectious episodes was noted after 12 months follow-up in children using the LPV/r regimen (p=0.006). There was a positive correlation between children whose baseline CD4+ values were greater than 500 cells/mm(3) and virological responses. Although virological responses to therapy were seen in about half the children (55.2%), the use of HAART containing LPV/r provided clinical and immmunological benefits.

Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives.

Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV) drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP) is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no country has yet approved it for use with adolescents. The aim of this review was to identify and summarize the evidence from studies on PrEP for adolescents. We have compiled and reviewed published studies focusing on safety, feasibility, adherence to therapeutics, self-perception, and legal issues related to PrEP in people aged between 10 and 24 years.

Bone mineral density and vitamin D concentration: the challenges in taking care of children and adolescents infected with HIV.

BACKGROUND: The increase in life expectancy for patients living with human immunodeficiency virus (HIV) infection has resulted in health complications related to a chronic disease. OBJECTIVES: To evaluate the prevalence of bone mineral density (BMD) alterations and vitamin D concentrations in HIV-infected children and adolescents and to verify the variations in those parameters during a 12-month interval. METHODS: A prospective cohort study with a dual period of evaluation was conducted in 57 patients perinatally HIV-infected and one patient with sexual abuse in early infancy. Demographic, anthropometric, pubertal stage, viral load, T CD4+ cell count and antiretroviral therapy were evaluated. Biochemical tests and total body (TB) and lumbar spine (L1-L4) bone density evaluations by dual X-ray absorptiometry (DXA) were performed. Calcium or vitamin D supplements were prescribed if reduction in BMD or deficiency for vitamin D was detected. RESULTS: 58 patients (ages 5.4-18.3 years; 60.3% girls) were included (T0); 55 patients were reevaluated after 12 (±3) months (T1). Low bone mass for chronological age was found in 6/58 (10.4%) and 6/55(10.9%) patients at T0 and at T1, respectively. There was no statistical relationship between z-scores for BMD (BMD z-score) and the variables sex, fracture history, family history of osteoporosis, physical activity and pubertal stage. There was a relation between BMD z-score alterations for TB and HIV viral load at T1 (p=0.016). There was no association between duration or classes of antiretroviral therapy and bone density. The mean value of vitamin D in T0 was 23.43ng/mL±2.015 and in T1 22.1ng/mL±0.707 and considered insufficient levels for this population. CONCLUSION: Patients infected with HIV are at risk for BMD alterations and lower vitamin D serum concentrations; both of these variables should be evaluated at routine examinations in order to improve both prevention and therapeutic planning.

HIV Viral Load Suppression in Adults and Children Receiving Antiretroviral Therapy-Results From the IeDEA Collaboration.

BACKGROUND: Having 90% of patients on antiretroviral therapy (ART) and achieving an undetectable viral load (VL) is 1 of the 90:90:90 by 2020 targets. In this global analysis, we investigated the proportions of adult and paediatric patients with VL suppression in the first 3 years after ART initiation. METHODS: Patients from the IeDEA cohorts who initiated ART between 2010 and 2014 were included. Proportions with VL suppression (<1000 copies/mL) were estimated using (1) strict intention to treat (ITT)-loss to follow-up (LTFU) and dead patients counted as having detectable VL; and (2) modified ITT-LTFU and dead patients were excluded. Logistic regression was used to identify predictors of viral suppression at 1 year after ART initiation using modified ITT. RESULTS: A total of 35,561 adults from 38 sites/16 countries and 2601 children from 18 sites/6 countries were included. When comparing strict with modified ITT methods, the proportion achieving VL suppression at 3 years from ART initiation changed from 45.1% to 90.2% in adults, and 60.6% to 80.4% in children. In adults, older age, higher CD4 count pre-ART, and homosexual/bisexual HIV exposure were associated with VL suppression. In children, older age and higher CD4 percentage pre-ART showed significant associations with VL suppression. CONCLUSIONS: Large increases in the proportion of VL suppression in adults were observed when we excluded those who were LTFU or had died. The increases were less pronounced in children. Greater emphasis should be made to minimize LTFU and maximize patient retention in HIV-infected patients of all age groups.