Suchergebnisse

IntroductionA dual split reporter protein system (DSP), recombining Renilla luciferase (RL) and green fluorescent protein (GFP) split into two different constructs (DSP1–7 and DSP8–11), was adapted to create a novel rapid phenotypic tropism assay (PTA) for HIV‐1 infection (DSP‐Pheno).MethodsDSP1–7 was stably expressed in the glioma‐derived NP‐2 cell lines, which expressed CD4/CXCR4 (N4X4) or CD4/CCR5 (N4R5), respectively. An expression vector with DSP8–11 (pRE11) was constructed. The HIV‐1 envelope genes were subcloned in pRE11 (pRE11‐env) and transfected into 293FT cells. Transfected 293FT cells were incubated with the indicator cell lines independently. In developing the assay, we selected the DSP1–7‐positive clones that showed the highest GFP activity after complementation with DSP8–11. These cell lines, designated N4R5‐DSP1–7, N4X4‐DSP1–7 were used for subsequent assays.ResultsThe env gene from the reference strains (BaL for R5 virus, NL4‐3 for X4 virus, SF2 for dual tropic virus) subcloned in pRE11 and tested, was concordant with the expected co‐receptor usage. Assay results were available in two ways (RL or GFP). The assay sensitivity by RL activity was comparable with those of the published phenotypic assays using pseudovirus. The shortest turnaround time was 5 days after obtaining the patient's plasma. All clinical samples gave positive RL signals on R5 indicator cells in the fusion assay. Median RLU value of the low CD4 group was significantly higher on X4 indicator cells and suggested the presence of more dual or X4 tropic viruses in this group of patients. Comparison of representative samples with Geno2Pheno [co‐receptor] assay was concordant.ConclusionsA new cell‐fusion‐based, high‐throughput PTA for HIV‐1, which would be suitable for in‐house studies, was developed. Equipped with two‐way reporter system, RL and GFP, DSP‐Pheno is a sensitive test with short turnaround time. Although maintenance of cell lines and laboratory equipment is necessary, it provides a safe assay system without infectious viruses. With further validation against other conventional analyses, DSP‐Pheno may prove to be a useful laboratory tool. The assay may be useful especially for the research on non‐B subtype HIV‐1 whose co‐receptor usage has not been studied much.

IntroductionA decreased frequency of unprotected sex during episodes of concurrent relationships may dramatically reduce the role of concurrency in accelerating the spread of HIV. Such a decrease could be the result of coital dilution – the reduction in per‐partner coital frequency from additional partners – and/or increased condom use during concurrency. To study the effect of concurrency on the frequency of unprotected sex, we examined sexual behaviour data from three communities with high HIV prevalence around Cape Town, South Africa.MethodsWe conducted a cross‐sectional survey from June 2011 to February 2012 using audio computer‐assisted self‐interviewing to reconstruct one‐year sexual histories, with a focus on coital frequency and condom use. Participants were randomly sampled from a previous TB and HIV prevalence survey. Mixed effects logistic and Poisson regression models were fitted to data from 527 sexually active adults reporting on 1210 relationship episodes to evaluate the effect of concurrency status on consistent condom use and coital frequency.ResultsThe median of the per‐partner weekly average coital frequency was 2 (IQR: 1–3), and consistent condom use was reported for 36% of the relationship episodes. Neither per‐partner coital frequency nor consistent condom use changed significantly during episodes of concurrency (aIRR=1.05; 95% confidence interval (CI): 0.99–1.24 and aOR=1.01; 95% CI: 0.38–2.68, respectively). Being male, coloured, having a tertiary education, and having a relationship between 2 weeks and 9 months were associated with higher coital frequencies. Being coloured, and having a relationship lasting for more than 9 months, was associated with inconsistent condom use.ConclusionsWe found no evidence for coital dilution or for increased condom use during concurrent relationship episodes in three communities around Cape Town with high HIV prevalence. Given the low levels of self‐reported consistent condom use, our findings suggest that if the frequency of unprotected sex with each of the sexual partners is sustained during concurrent relationships, HIV‐positive individuals with concurrent partners may disproportionately contribute to onward HIV transmission.

The benefits of long‐term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone loss. In addition, the dyslipidemia mainly seen with protease inhibitors may increase the risk of cardiovascular disease in adulthood and potentially in children as they mature into adults. Nucleoside reverse transcriptase inhibitors, particularly stavudine, zidovudine and didanosine are linked to development of LD and lactic acidosis. Perinatally infected children initiate ART early in life; they require lifelong therapy with multiple drug regimens leading to varying toxicities, all potentially impacting their quality of life. LD has a significant impact on the mental health of older children and adolescents leading to poor self‐image, depression and subsequent poor adherence to therapy. Reduced bone mineral density (BMD) is reported in both adults and children on ART with the potential for children to develop more serious bone complications than adults due to their rapid growth spurts and puberty. The role of vitamin D in HIV‐associated osteopenia and osteoporosis is not clear and needs further study. Most resource‐limited settings are unable to monitor lipid profiles or BMD, exposing infected children and adolescents to on‐going toxicities with unclear long‐term consequences. Improved interventions are urgently needed to prevent and manage these metabolic complications. Longitudinal cohort studies in this area should remain a priority, particularly in resource‐limited settings where the majority of infected children reside.

IntroductionAntiretroviral therapy (ART) has rendered HIV and AIDS a chronic condition for individuals in many parts of the world. Adherence, however, is integral to achieving chronicity. Studies have shown both relatively high ART adherence rates in sub‐Saharan Africa and the importance of community home‐based care (CHBC) to facilitating this process. In light of diminished HIV and AIDS funding globally and increased reliance on CHBC throughout Africa, a better understanding of how CHBC may strengthen ART adherence is essential to improving patients' quality of life, tending to the needs of care supporters and achieving healthier populations.MethodsThis article reports findings from a qualitative study of a CHBC organiztion serving an estimated 2500 clients in rural Swaziland. Semi‐structured questionnaires with 79 HIV‐positive clients [people living with HIV and AIDS (PLWHA)] yielded data on diverse aspects of being HIV positive, including insights on whether and how PLWHA perceived care supporters to facilitate ART adherence in a high stigma and structurally impoverished setting.ResultsNinety‐two percent of participants said their health had improved since care supporters came into their lives. A major finding was that an estimated 53% of participants said they would have died, a few from suicide had the care supporter never intervened. More than one in four participants (27.9%) sought HIV testing after a care supporter began visiting them. Nearly a third (31%) commenced ART after and largely as a consequence of care supporter intervention. Approximately one in four (23%) reported that their care supporter had helped them to disclose their HIV‐positive status to family members. Twenty‐seven percent said they had felt discouraged or had been discouraged from taking ART by members of their family or community.DiscussionGeneral inductive analysis of participant reports suggested two social mechanisms of CHBC impact on ART adherence: (i) cultivating client‐care supporter "talk" to enhance treatment uptake and literacy, reduce felt stigma and challenge social pressures to desist from ART and (ii) real‐time interactions between clients and care supporters whereby the care "relationship" was itself the "intervention," providing lay counsel, material and financial assistance, and encouragement when clients suffered stigma, side effects and other obstacles to adherence. These social dynamics of adherence generally fall outside the purview of conventional clinical and public health research.ConclusionsPLWHA reports of care supporter practices that enabled ART adherence demonstrated the pivotal role that CHBC plays in many PLWHA lives, especially in hard to reach areas. Relative to clinic personnel, care supporters are often intensely engaged in clients' experiences of sickness, stigma and poverty, rendering them influential in individuals' decision‐making. This influence must be matched with on‐going training and support of care supporters, as well as a clear articulation with the formal and informal health sectors, to ensure that PLWHA are correctly counselled and care supporters themselves supported. Overall, findings showed that PLWHA experiences of CHBC should be captured and incorporated into any programme aimed at successfully implementing the Joint United Nations Programme on HIV and AIDS (UNAIDS) Treatment 2.0 agenda Pillar 4 (increasing HIV testing uptake and care linkages) and Pillar 5 (strengthening community mobilization).

IntroductionThe provision of HIV treatment and care in sub‐Saharan Africa faces multiple challenges, including weak health systems and attrition of trained health workers. One potential response to overcome these challenges has been to engage community health workers (CHWs).MethodologyA systematic literature search for quantitative and qualitative studies describing the role and outcomes of CHWs in HIV care between inception and December 2012 in sub‐Saharan Africa was performed in the following databases: PubMed, PsychINFO, Embase, Web of Science, JSTOR, WHOLIS, Google Scholar and SAGE journals online. Bibliographies of included articles were also searched. A narrative synthesis approach was used to analyze common emerging themes on the role and outcomes of CHWs in HIV care in sub‐Saharan Africa.ResultsIn total, 21 studies met the inclusion criteria, documenting a range of tasks performed by CHWs. These included patient support (counselling, home‐based care, education, adherence support and livelihood support) and health service support (screening, referral and health service organization and surveillance). CHWs were reported to enhance the reach, uptake and quality of HIV services, as well as the dignity, quality of life and retention in care of people living with HIV. The presence of CHWs in clinics was reported to reduce waiting times, streamline patient flow and reduce the workload of health workers. Clinical outcomes appeared not to be compromised, with no differences in virologic failure and mortality comparing patients under community‐based and those under facility‐based care. Despite these benefits, CHWs faced challenges related to lack of recognition, remuneration and involvement in decision making.ConclusionsCHWs can clearly contribute to HIV services delivery and strengthen human resource capacity in sub‐Saharan Africa. For their contribution to be sustained, CHWs need to be recognized, remunerated and integrated in wider health systems. Further research focusing on comparative costs of CHW interventions and successful models for mainstreaming CHWs into wider health systems is needed.

IntroductionHuman APOBEC3G/F (hA3G/F) restricts retroviral replication through G‐to‐A hypermutations, which can generate drug‐resistant progenies in vitro. The clinical relevance is still inconclusive. To bridge this gap, we aim to study the role of these hypermutations in evolution of drug resistance; we characterised hA3G/F‐mediated hypermutations in the RT region of the pol gene of patients with or without antiretroviral therapy (ART).MethodsIn 88 HIV‐1‐positive individuals, drug resistance genotyping was carried out in plasma virus and provirus by population sequencing. Hypermutations were determined by three different approaches using Hypermut 2.0 software, cluster analysis and APOBEC3G‐mediated defectives indices. Clinical and demographic characteristics of these individuals were studied in relation to these hypermutations.ResultshA3G/F‐mediated hypermutated sequences in proviral DNA, but not in plasma virus, were identified in 11.4% (10/88) subjects. Proviral hypermutations were observed more frequently in patients with ART failure than in ART‐naïve individuals (p=0.03). In therapy failure patients, proviral hypermutation were associated with greater intra‐compartmental genetic diversity (p<0.001). In therapy‐naïve individuals, hypermutated proviral DNA with M184I and M230I mutations due to the editing of hA3G, had stop codons in the open reading frames and the same mutations were absent in the plasma virus. Only a limited concordance was found between the drug resistance mutations in plasma RNA and proviral DNA.ConclusionshA3G lethal hypermutation was significantly associated with ART failure in Indian HIV‐1 subtype C patients. It is unlikely that viral variants, which exhibit hypermutated sequences and M184I and/or M230I, will mature and expand in vivo.

The long‐term impact on bone health of lifelong HIV infection and prolonged ART in growing and developing children is not yet known. Measures of bone health in youth must be interpreted in the context of expected developmental and physiologic changes in bone mass, size, density and strength that occur from fetal through adult life. Low bone mineral density (BMD) appears to be common in perinatally HIV‐infected youth, especially outside of high‐income settings, but data are limited and interpretation complicated by the need for better pediatric norms. The potential negative effects of tenofovir on BMD and bone mass accrual are of particular concern as this drug may be used more widely in younger children. Emphasizing good nutrition, calcium and vitamin D sufficiency, weight‐bearing exercise and avoidance of alcohol and smoking are effective and available approaches to maintain and improve bone health in all settings. More data are needed to inform therapies and monitoring for HIV‐infected youth with proven bone fragility. While very limited data suggest lack of marked increase in fracture risk for youth with perinatal HIV infection, the looming concern for these children is that they may fail to attain their expected peak bone mass in early adulthood which could increase their risk for fractures and osteoporosis later in adulthood.

IntroductionIn April 2010, tenofovir replaced stavudine in public‐sector first‐line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir‐based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa.MethodsThis was a cohort analysis of treatment‐naïve, non‐pregnant adult patients initiated on ART between April 2004 and December 2011. First‐line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir was substituted for stavudine after April 2010. We evaluated the frequency and type of single‐drug substitutions (excluding switches to second‐line therapy). Cox models were used to evaluate the association of ART initiation year and antiretroviral drug type with single‐drug substitutions in the first 12 months on treatment.ResultsOne thousand nine hundred and sixty‐four (10%) substitutions occurred amongst 19,699 patients. Excluding 2004 (year of treatment roll‐out), before 2010 one‐year single‐drug substitutions ranged from 10.0 to 13.1%. In 2011, well after integration of tenofovir, substitutions decreased to 5.6%. Single‐drug substitution was lowest amongst patients on tenofovir (5.1%) versus zidovudine (11.3%), 30 mg stavudine (10.5%) or 40 mg stavudine (14.4%). Adjusted Cox models showed that patients initiating treatment between 2005 and 2010 (vs. 2011) had a twofold increased hazard of single‐drug substitution, while those on zidovudine or stavudine had a two to threefold increase in single‐drug substitution versus tenofovir patients in the first 12 months on ART.ConclusionsThe decline in single‐drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource‐limited settings.

IntroductionSimultaneous use of contraceptive hormones and anti‐retroviral therapy (ART) may theoretically lessen the effectiveness of both. Women on ART need assurance that hormonal contraception is safe and effective. The sub‐dermal implant is an ideal product to study: low and steady progestin release and no adherence uncertainties. We sought to determine if the medications' effectiveness is compromised.MethodsWe conducted a prospective cohort study among women on first line ART (stavudine or zidovudine and lamivudine+nevirapine). We recruited new implant users and matched them to women not using hormonal contraception, based on age and baseline CD4. Participants were followed prospectively for up to two years, recording serial CD4 measures and medical histories. We used generalized growth curve models and Wald chi‐square tests to compare changes in CD4 counts across study groups. Prospective CD4 measures were censored (excluded) if any of the following events occurred: change in ART, implant removal or use of any hormonal contraception among controls. We examined incidence of opportunistic infection and pregnancy.ResultsWe matched 48 implant users to 33 non‐hormonal controls. Over time, CD4 counts for both groups rose slightly but did not deviate significantly from each other (p=0.44). Opportunistic infection rates did not differ between the groups. None of the implant users and one of the non‐hormonal controls became pregnant during follow‐up.ConclusionsThis small study found concurrent use of contraceptive implants and ART to be safe and effective. Although other hormonal contraceptive products and ART regimens may interact in unknown ways, the results of this study are reassuring.

IntroductionThe scale‐up of highly active antiretroviral therapy (HAART) has led to a significant improvement in survival of the HIV‐positive patient but its effects on health‐related quality of life (HRQOL) are less known and context‐dependent. Our aim was to assess the temporal changes and factors associated with HRQOL among HIV‐positive adults initiating HAART in Burkina Faso.MethodsHIV‐positive people initiating HAART were prospectively included and followed over a one‐year period in three HIV clinics of Ouagadougou. HRQOL was assessed at baseline and at each follow‐up visit using physical (PHS) and mental (MHS) summary scores derived from the Medical Outcome Study 36‐Item short‐form health survey (MOS SF‐36) questionnaire. Toxicity related to HAART modification and self‐reported symptoms were recorded during follow‐up visits. Determinants associated with baseline and changes in both scores over a one‐year period were assessed using a mixed linear model.ResultsA total of 344 patients were included. Their median age at baseline was 37 years [interquartile range (IQR) 30–44] and their median CD4 count was 181 cells/mm3 (IQR 97–269). The mean [standard deviation (SD)] PHS score increased from 45.4 (11.1) at baseline to 60.0 (3.1) at 12 months (p<10−4) and the mean (SD) MHS score from 42.2 (8.7) to 43.9 (3.4) (p<10−2). After one year of treatment, patients that experienced on average two symptoms during follow‐up presented with significantly lower PHS (63.9) and MHS (43.8) scores compared to patients that presented no symptoms with PHS and MHS of 68.2 (p<10−4) and 45.3 (p<10−3), respectively.DiscussionThe use of HAART was associated with a significant increase in both physical and mental aspects of the HRQOL over a 12‐month period in this urban African population. Perceived symptoms experienced during follow‐up visits were associated with a significant impairment in HRQOL. The appropriate and timely management of reported symptoms during the follow‐up of HAART‐treated patients is a key component to restore HRQOL.

IntroductionWe studied the frequency of documentation of disclosure of HIV status in medical charts and its correlates among HIV‐infected adolescents in 2009, in Abidjan, Côte d'Ivoire.MethodsThe PRADO‐CI is a cross‐sectional study aimed at studying HIV‐infected adolescents' social, psychological, and behavioural difficulties and their determinants in Abidjan, Côte d'Ivoire. In this study, we present specific analyses on disclosure. All HIV‐infected adolescents aged 13–21 years and followed at least once in 2009 in two urban HIV‐care centres in Abidjan (Cepref and Yopougon Teaching Hospital) were enrolled in the study. Standardized data were extracted from medical records to document if there was notification of disclosure of HIV status in the medical record. Frequency of notification of HIV disclosure was estimated with its 95% confidence interval (CI) and correlates were analyzed using logistic regression.ResultsIn 2009, 229 adolescents were included: 126 (55%) males; 93% on antiretroviral therapy (ART), 61% on cotrimoxazole prophylaxis. Their median age was 15 years at the time of the study. Among the 193 patients for whom information on HIV status disclosure was documented (84%), only 63 (32.6%; 95% CI=26.0–39.3%) were informed of their status. The proportion of adolescents informed increased significantly with age: 19% for 13–15 years, 33% for 16–18 years and 86% for 19–21 years (p <0.0001). Adolescents on ART tended to be more likely to be informed of their HIV status (34.5%) than those not treated (13.3%) (p=0.11). Those on cotrimoxazole were significantly more likely to be informed (39.6%) than those not (21.9%) (p=0.01). Disclosure was significantly higher in adolescents with a history of ART regimen change (p=0.003) and in those followed in the Cepref (48.4%) compared to the Yopougon Teaching Hospital (24.8%), (p=0.001). In multivariate analyses, disclosed HIV status was significantly higher in those followed‐up in the Cepref compared to the other centre: adjusted odds ratio (aOR)=3.5 (95% CI: 1.1–10.9), and among older adolescents compared to those aged 13–15 years: [16–18 years] aOR=4.2 (95% CI: 1.5–11.5) and [>18 years]: aOR=22.1 (95% CI: 5.2–93.5).ConclusionsHIV disclosure rate was low among Ivoirian HIV adolescents and was site‐ and age‐dependent. There is a need for practical interventions to support HIV disclosure to adolescents which provides age‐appropriate information about the disease.

IntroductionCervical infection with high‐risk human papillomavirus (HRHPV) induces cervical cancer and is present in 14% of women in Europe. We assessed the prevalence and incidence of cervical HRHPV in a cohort of HIV‐positive women living in Belgium.MethodsProspective observational program of screening and follow up of HRHPV cervical infection performed by Hybrid Capture in 825 HIV‐positive women between 2002 and 2011. Women without normal cervix at baseline were excluded.ResultsThe final analysis included 652 women: median age 38 years, African origin (81%), median HIV follow‐up (66 months), median CD4 count (426 cells/μL) and 79% on antiretroviral therapy (cART). At baseline, HRHPV prevalence was 43% and decreased significantly as both age and CD4 cell count increased: highest prevalence (100%) in women <30 years and <200 CD4/μL and lowest (19%) in women >40 years and >500 CD4/μL (p<0.0001, multivariate analysis). The relative risk (RR) to carry HRHPV at baseline decreases proportionally by 11% for each 5 years‐age increase and by 11% for each 100 CD4 cells/μL rise (RR=0.89, 95% CI: 0.85‐0.93; p<0.0001, Poisson regression for both). During follow‐up, incidence rate of HRHPV was 13.4 per 100 women‐years.ConclusionsWe found a high HRHPV prevalence of 43% and an incidence rate of 13 per 100 women‐years in this cohort of HIV‐positive women living in Europe and on cART. Women under 40 years‐age had the highest prevalence even with CD4 count >350 cells/μL. The magnitude of HRHPV epidemiology should prompt to evaluate the clinical efficacy of vaccines against HPV in HIV‐infected women.