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IntroductionHuman immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late‐stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi‐agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis.DiscussionBefore highly active antiretroviral therapy (HAART), the two‐to‐five‐year incidence of symptomatic heart failure ranged from 4 to 28% in HIV patients. Patients both before and after HAART also frequently have asymptomatic abnormalities in cardiovascular structure. Echocardiographic measurements indicate left ventricular (LV) systolic dysfunction in 18%, LV hypertrophy in 6.5%, and left atrial dilation in 40% of patients followed on HAART therapy. Diastolic dysfunction is also common in long‐term survivors of HIV infection. Accelerated atherosclerosis has been found in HIV‐infected young adults and children without traditional coronary risk factors. Infective endocarditis, although rare in children, has high mortality in late‐stage AIDS patients with poor nutritional status and severely compromised immune systems. Although lymphomas have been found in HIV‐infected children, the incidence is low and cardiac malignancy is rare. Rates of congenital cardiovascular malformations range from 5.6 to 8.9% in cohorts of HIV‐uninfected and HIV‐infected children with HIV‐infected mothers. In non‐HIV‐infected infants born to HIV‐infected mothers, foetal exposure to ART is associated with reduced LV dimension, LV mass, and septal wall thickness and with higher LV fractional shortening and contractility during the first two years of life.ConclusionsRoutine, systematic, and comprehensive cardiac evaluation, including a thorough history and directed laboratory assays, is essential for the care of HIV‐infected adults and children as cardiovascular illness has become a part of care for long‐term survivors of HIV infection. The history should include traditional risk factors for atherosclerosis, prior opportunistic infections, environmental exposures, and therapeutic and illicit drug use. Laboratory tests should include a lipid profile, fasting glucose, and HIV viral load. Asymptomatic cardiac disease related to HIV can be fatal, and secondary effects of HIV infection often disguise cardiac symptoms, so systematic echocardiographic monitoring is warranted.

IntroductionDue to highly active antiretroviral therapy (HAART), HIV‐1 infection has evolved from a lethal to a chronic disease. As such, health‐related quality of life (HRQoL) has become an important outcome variable. The purpose of this study was to identify socio‐economic, behavioural, (neuro)psychological and clinical determinants of HRQoL among people living with HIV (PLHIV).MethodsThis study was conducted between 1 January and 31 December 2012 at the AIDS Reference Centre of Ghent University Hospital, a tertiary care referral centre in Belgium. Validated self‐report questionnaires were administered to collect socio‐demographic data, to assess HRQoL (Medical Outcomes Study‐HIV), depressive symptoms (Beck Depression Inventory‐II) and adherence to HAART (Short Medication Adherence Questionnaire) and to screen for neurocognitive dysfunction.ResultsA total of 237 people participated, among whom 187 (78.9%) were male. Mean age was 45.8±10.7 years and 144 (63.7%, 144/226) participants were homosexual. Median physical and mental health score (PHS, MHS) were 55.6 (IQR 48.2–60.6) and 52.0 (IQR 44.2–57.9), respectively. Multivariable regression analysis revealed that incapacity to work, depressive symptoms, neurocognitive complaints (NCCs), dissatisfaction with the patient–physician relationship and non‐adherence were all negatively associated with HRQoL.ConclusionsSocio‐economic (work status), behavioural (adherence) and (neuro)psychological (depressive symptoms, NCCs) determinants independently impact HRQoL among this cohort of PLHIV. Clinical parameters (viral load, CD4 cell count) were not independently associated with HRQoL.

The great success in the prevention and treatment of pediatric HIV in high resource countries, and now in low resource countries, has changed the face of the HIV epidemic in children from one of near certain mortality to that of a chronic disease. However, these successes pose new challenges as perinatally HIV‐infected youth survive into adulthood. Increased survival of HIV‐infected children is associated with challenges in maintaining adherence to what is likely life‐long therapy, and in selecting successive antiretroviral drug regimens, given the limited availability of pediatric formulations, limitations in pharmacokinetic and safety data of drugs in children, and the development of extensive drug resistance in multi‐drug‐experienced children. Pediatric HIV care must now focus on morbidity related to long‐term HIV infection and its treatment. Survival into adulthood of perinatally HIV‐infected youth in high resource countries provides important lessons about how the epidemic will change with increasing access to antiretroviral therapy for children in low resource countries. This series of papers will focus on issues related to management of perinatally infected youth and young adults.

IntroductionIncreasing the uptake of HIV testing and decreasing the number of undiagnosed people is a priority for HIV prevention. Understanding the barriers that hinder people from testing is vital, particularly when working with especially vulnerable populations like migrants. Most data available on migrants are based on African migrants in the UK, while barriers to HIV testing in Latin‐American migrants living in Europe remain unexplored. Still, they account for a quarter of new diagnosis in Spain and suffer higher rates of delayed diagnosis.MethodsBetween May 2008 and March 2011, a mobile unit offered free rapid HIV tests in different Spanish cities. We compared the prevalence of no previous testing, adjusting for potential confounders by two multivariate logistic models, and described differences in perceived barriers to testing in Latin‐American migrants living in Spain versus Spaniards. Participants included men who have sex with men (MSM), men who have sex exclusively with women (MSW), and women.ResultsOf the 5920 individuals who got tested and answered a self‐administered questionnaire, 36.5% were MSM (20.4% previously untested), 28.9% were MSW (49% previously untested) and 34.6% were women (53% previously untested). Almost one quarter were Latin‐American, of whom 30% had never been tested versus 45% of untested Spaniards. After adjusting for potential confounders, Spaniards were more likely to report no previous testing than Latin‐Americans among women and MSW all together (Odds Ratio (OR)=2.0; 95% Confidence Interval (CI): 1.7–2.4) and among MSM (OR=1.6; 95% CI: 1.2–2.0). Among the 2455 who had never undergone an HIV test before, main barriers to testing were low perceived risk (54% Spaniards vs. 47% Latin‐American) and concerns arising from the loss of anonymity (19.5% vs. 16.9%). Fear of rejection or discrimination and fear of legal problems were a barrier for <2%.ConclusionsLatin‐American migrants living in Spain were more likely to get tested than Spaniards. Regardless of nationality, low perceived risk was the main barrier to testing whereas fear of stigma or discrimination and fear of legal problems were merely incidental. However, new Spanish austerity policies regarding healthcare for migrants in response to the economic crisis may reverse this situation.

The 2013 World Health Organization's (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource‐limited settings.The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm3 or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm3); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV‐positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first‐line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once‐daily fixed‐dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task‐shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources most efficiently.

After two decades of microbicide clinical trials it remains uncertain if vaginally‐ delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre‐licensure implementation trials, Phase IV post‐marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large‐scale microbicide efficacy trials completed to‐date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post‐marketing research, and microbicide introduction and delivery programs.

IntroductionEarly initiation of antiretroviral therapy (ART) in eligible pregnant women is a key intervention for prevention of mother‐to‐child transmission (PMTCT) of HIV. However, in many settings in sub‐Saharan Africa where ART‐eligibility is determined by CD4 cell counts, limited access to laboratories presents a significant barrier to rapid ART initiation. Point‐of‐care (POC) CD4 cell count testing has been suggested as one approach to overcome this challenge, but there are few data on the agreement between POC CD4 cell enumeration and standard laboratory‐based testing.MethodsWorking in a large antenatal clinic in Cape Town, South Africa, we compared POC CD4 cell enumeration (using the Alere PimaTM Analyzer) to laboratory‐based flow cytometry in consecutive HIV‐positive pregnant women. Bland–Altman methods were used to compare the two methods, including analyses by subgroups of participant gestational age.ResultsAmong the 521 women participating, the median gestational age was 23 weeks, and the median CD4 cell count according to POC and laboratory‐based methods was 388 and 402 cells/µL, respectively. On average, the Pima POC test underestimated CD4 cell count relative to flow cytometry: the mean difference (laboratory test minus Pima POC) was 22.7 cells/µL (95% CI, 16.1 to 29.2), and the limits of agreement were −129.2 to 174.6 cells/µL. When analysed by gestational age categories, there was a trend towards increasing differences between laboratory and POC testing with increasing gestational age; in women more than 36 weeks' gestation, the mean difference was 45.0 cells/µL (p=0.04).DiscussionThese data suggest reasonable overall agreement between Pima POC CD4 testing and laboratory‐based flow cytometry among HIV‐positive pregnant women. The finding for decreasing agreement with increasing gestational age requires further investigation, as does the operational role of POC CD4 testing to increase access to ART within PMTCT programmes.

Previous research on the use of personal lubricants for sexual intercourse is limited and has primarily focused on condom compatibility and breakage, with only recent limited assessment of lubricant safety and possible epidemiologic implications. This article discusses the global evidence of lubricant compatibility with latex condoms and biological safety of lubricants, as well as documentation of lubricant use and current guidelines for HIV prevention programming in Africa. Data on lubricant compatibility with condoms are less available than commonly realized, and many lubricant products may not have been thoroughly tested for safety due to flexible regulatory environments. Recent laboratory and study findings from microbicides research also suggest that some water‐based lubricants may have safety issues. Some African populations are using several types of lubricants, especially oil‐based petroleum jellies, and receive little evidence‐based guidance. More research is needed from the medical community to guide prevention programming.

IntroductionRetention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been well‐characterized.MethodsWe examined data on 37,352 adult pre‐ART patients (ART ineligible or unknown eligibility) who enrolled in care during 2005–2008 with >1 clinical visit at 23 clinics in Mozambique. We defined loss to clinic (LTC) as >12 months since the last visit among those not known to have died/transferred. Cox proportional‐hazards models were used to examine factors associated with LTC, accounting for clustering within sites.ResultsOf 37,352 pre‐ART patients, 61% had a CD4 count within three months of enrolment (median CD4: 452, IQR: 345–611). 17,598 (47.1%) were ART ineligible and 19,754 (52.9%) were of unknown eligibility status at enrolment because of missing information on CD4 count and/or WHO stage. Kaplan‐Meier estimates for LTC at 12 months were 41% (95% CI: 40.2–41.8) and 48% (95% CI: 47.2–48.8), respectively. Factors associated with LTC among ART ineligible patients included male sex (AHRmen_vs_non‐pregnant women: 1.5; 95% CI: 1.4–1.6) and being pregnant at enrolment (AHRpregnant_vs_non‐pregnant women: 1.3; 95% CI: 1.1–1.5). Older age, more education, higher weight and more advanced WHO stage at enrolment were independently associated with lower risks of LTC. Similar findings were observed among patients whose ART eligibility status was unknown at enrolment.ConclusionsSubstantial LTC occurred prior to ART initiation among patients not yet known to be eligible for ART, including nearly half of patients without documented ART eligibility assessment. Interventions are needed to target pre‐ART patients who may be at higher risk for LTC, including pregnant women and patients with less advanced HIV disease.

IntroductionTenofovir (TDF) with emtricitabine (FTC) and zidovudine (ZDV) is a recognized alternate first‐line antiretroviral (ART) regimen for patients who cannot start treatment with non‐nucleoside reverse transcriptase inhibitors (NNRTIs). Clinical studies comparing TDF+FTC+ZDV to other regimens are lacking.MethodsParticipants in a trial of early ART in Côte d'Ivoire (Temprano ANRS 12136) started treatment with TDF/FTC plus either efavirenz (EFV) or ZDV (HIV‐1+2 dually infected patients and women refusing contraception or previously treated with nevirapine). We compared rates of upper digestive serious adverse events (sAEs) between TDF/FTC+EFV and TDF/FTC+ZDV patients during the first six months of treatment. sAEs were defined as either grade 3–4 AEs or persistent grade 1–2 AEs leading to drug discontinuation.ResultsA total of 197 patients (76% women, median CD4 count 395/mm3) started therapy with TDF/FTC, 126 with EFV and 71 with ZDV. During the first six months of ART, 94 patients had digestive AEs (nausea/vomiting) of any grade (EFV 36/126, 29%; ZDV 58/71, 82%, p<0.0001), including 20 sAEs (EFV 3/126, 5%; ZDV 17/71, 24%, p<0.0001). In‐patients on TDF/FTC+ZDV with digestive AEs, the median time to the first symptom was two days (IQR: 1–4). Plasma ZDV (Cmax) distributions and pill ZDV dosages were normal. Patients with digestive AEs had higher haemoglobin levels and tended to have higher body mass indices and more frequent past histories of cotrimoxazole (CTX) prophylaxis.ConclusionsWe observed an unexpectedly high rate of digestive sAEs in West African adults, mostly women, who started a 3‐nuc ART with TDF/FTC+ZDV in Côte d'Ivoire. These adults were participating in a trial of early ART and had much higher CD4 counts than those who currently routinely start ART in sub‐Saharan Africa. They all received CTX concomitantly with ZDV. We suggest that further early prescriptions of TDF+XTC+ZDV should be carefully monitored and that whenever possible, the rate of early upper digestive adverse events should be compared to that occurring in‐patients taking other drug regimens.Clinical Trial Number: NCT00495651.

Three decades into the HIV/AIDS epidemic there is a growing cohort of perinatally HIV‐infected adolescents globally. Their survival into adolescence and beyond represent one of the major successes in the battle against the disease that has claimed the lives of millions of children. This population is diverse and there are unique issues related to antiretroviral treatment and management. Drawing from the literature and experience, this paper discusses several broad areas related to antiretroviral management, including: 1) diverse presentation of HIV, (2) use of combination antiretroviral therapy including in the setting of co‐morbidities and rapid growth and development, (3) challenges of cART, including nonadherence, resistance, and management of the highly treatment‐experienced adolescent patient, (4) additional unique concerns and management issues related to PHIV‐infected adolescents, including the consequences of longterm inflammation, risk of transmission, and transitions to adult care. In each section, the experience in both resource‐rich and limited settings are discussed with the aim of highlighting the differences and importantly the similarities, to share lessons learnt and provide insight into the multi‐faceted approaches that may be needed to address the challenges faced by this unique and resilient population.

IntroductionIndividuals with intellectual disabilities are rarely targeted by the current human immunodeficiency virus (HIV) response, thereby reducing their access to HIV information and services. Currently, little is known about the HIV knowledge and sexual practices of young Nigerians with intellectual disabilities. Thus, this study sought to compare the HIV knowledge and sexual practices of learners with mild/moderate intellectual disabilities and non‐disabled learners (NDL) in Nigeria. Findings could help in the development of HIV interventions that are accessible to Nigerian learners with intellectual impairments.MethodsThis cross‐sectional, comparative study utilized a survey to investigate HIV knowledge and sexual practices among learners with mild/moderate intellectual disabilities and NDL in Nigeria. Learners with mild/moderate intellectual disabilities (n=300) and NDL (n=300) within the age range of 12 to 19 years drawn from schools across Oyo State, Nigeria, completed a structured questionnaire to assess their knowledge of HIV transmission and sexual practices.ResultsSignificantly more learners with mild/moderate intellectual disabilities (62.2%) than NDL 48 (37.8%) reported having sexual experience (p=0.002). Of the sexually experienced female learners with mild/moderate intellectual disabilities, 28 (68.3%) reported history of rape compared with 9 (2.9%) of female NDL (p=0.053). Intellectual impairment was significantly associated with lower HIV transmission knowledge scores (p<0.001). Learners with mild/moderate intellectual disabilities were less likely than NDL (p<0.001) to have heard about HIV from most of the common sources of HIV information. In addition, when compared with non‐disabled learners, learners with mild/moderate intellectual disabilities were significantly more likely to have reported inconsistent condom use with boyfriends/girlfriends (p<0.001), with casual sexual partners (p<0.001) and non‐use of condom during last sexual activity (p<0.001).ConclusionsFindings suggest that adolescents with intellectual impairments are at higher risk of HIV infection than their non‐disabled peers. This gap could be addressed through interventions that target Nigerians with intellectual impairments with accessible HIV information and services.