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Objectives: HIV virological failure remains a major threat to programme success in sub‐Saharan Africa. While HIV drug resistance (HIVDR) and inadequate adherence are the main drivers of virological failure, the individual, clinical and health system characteristics that lead to poor outcomes are not well understood. The objective of this paper is to identify those characteristics among people failing first‐line antiretroviral therapy (ART). Methods: We enrolled a cohort of adults in HIV care experiencing virological failure on first‐line ART at five sites and used standard statistical methods to characterize them with a focus on three domains: individual/demographic, clinical, and health system, and compared each by country of enrolment. Results: Of 840 participants, 51% were women, the median duration on ART was 3.2 years [interquartile range (IQR) 1.1, 6.4 years] and the median CD4 cell count prior to failure was 281 cells/µL (IQR 121, 457 cells/µL). More than half of participants [53%; 95% confidence interval (CI) 49–56%] stated that they had > 90% adherence and 75% (95% CI 72–77%) took their ART on time all or most of the time. Conversely, the vast majority (90%; 95% CI 86–92%) with a completed genotypic drug resistance test had any HIV drug resistance. This population had high health system use, reporting a median of 3 (IQR 2.6) health care visits and a median of 1 (IQR 1.1) hospitalization in the preceding 6 months. Conclusions: Patients failing first‐line ART in sub‐Saharan Africa generally report high rates of adherence to ART, have extremely high rates of HIV drug resistance and utilize significant health care resources. Health systems interventions to promptly detect and manage treatment failure will be a prerequisite to establishing control of the HIV epidemic. [ABSTRACT FROM AUTHOR]

Objectives: Despite recent pharmacological progress, memory impairment is still frequently reported in people living with HIV. We aimed to conduct a systematic literature review investigating the presence of impairment of (sub)components of memory function in patients prescribed highly active antiretroviral therapy (ART). Methods: We adopted a cognitive neuropsychological model of memory function as the theoretical framework, distinguishing between a short‐term working memory component and a long‐term component of memory, along with their specific (sub)components. We systematically searched for the presence of impairment of each (sub)component in the selected papers. Careful consideration was given to study design and methods and control of covariates. Results: Only the central executive component of working memory has been consistently reported to be impaired in HIV infection. The other two (sub)components, namely the phonological loop and the visuospatial sketchpad, were unimpaired. Discordant results have been obtained as to verbal and visual episodic memory, as some authors reported an association with HIV infection, whereas others did not. There is little evidence for semantic memory deficit in HIV infection, while there are suggestions that the neural substrate of implicit memory may be damaged by the effects of HIV infection and inflammation. Most studies in this area have been conducted in small samples and with poor control for covariates. Thus, conclusions regarding the association of memory dysfunction with HIV infection are hampered by methodological issues such as selection bias and unmeasured confounding. Conclusions: The task remains for future research to ascertain the impact of HIV infection on memory function. [ABSTRACT FROM AUTHOR]

Objectives The aim of the paper was to describe the association of religion with HIV outcomes in newly diagnosed Africans living in London. Methods A survey of newly diagnosed HIV-positive Africans attending 15 HIV treatment centres across London was carried out between April 2004 and February 2006. Confidential self-completed questionnaires were used, linked to clinical records. Bivariate analyses were conducted to ascertain whether religious beliefs were associated with late diagnosis, antiretroviral therapy, and immunological and virological outcome 6 months post diagnosis. Results A total of 246 Black Africans were eligible and included in the analysis: 62.6% were women, and the median age was 34 years. The median CD4 count at diagnosis was 194 cells/ μL (range 0-1334 cells/ μL) and 75.6% presented late, as defined as a CD4 count < 350 cells/ μL. Most participants were religious: non- Roman Catholic Christians (55.7%), Roman Catholics (35.2%) and Muslims (6.1%). Only 1.2% stated that they did not have a religion. Participants who attended religious services at least monthly were more likely to believe that 'faith alone can cure HIV' than those who attended less frequently (37.7% vs. 15.0%; P = 0.002). A small proportion (5.2%) believed that taking antiretroviral therapy implied a lack of faith in God. Bivariate analysis found no relationship between religiousness (as measured using frequency of attendance at religious services and religious attitudes or beliefs) and late diagnosis, changes in CD4 count/viral load 6 months post diagnosis, or initiation of antiretroviral therapy. Conclusions Strong religious beliefs about faith and healing are unlikely to act as a barrier to accessing HIV testing or antiretroviral treatment for Black Africans living in London. [ABSTRACT FROM AUTHOR]

Background: Women with HIV are more often infected with human papillomavirus (HPV) and are more prone to develop precancerous cervical lesions (squamous intraepithelial lesions, SIL) and invasive cervical cancer (ICC) than HIV‐negative women. Objective: This scoping‐review analyses the impact of HIV on HPV prevalence, incidence and evolution to SIL and ICC. Methods: We selected all PubMed systematic reviews and meta‐analyses published between January 2000 and July 2021 reporting data about HPV, cervical intraepithelial neoplasia (CIN), SIL and ICC prevalence, incidence and evolution in women with HIV. A hypothetical model comparing the history of HPV infection in HIV‐negative, combined antiretroviral therapy (cART)‐treated and ‐untreated women with HIV was built. Results: Data from 11 meta‐analyses and 10 systematic reviews were selected, which included between 770 and 236 127 women with HIV. Women with HIV have a 3 to 6 times higher risk of being infected by HPV, of progression to high‐grade SIL (HSIL) and to ICC. These risks are exacerbated when the CD4 cell counts are low and when they are not using cART, whereas these risks are reduced by 20%–30% when they are optimally treated with cART and have had a suppressed HIV viral load for at least 2 years. In our model, we illustrated that optimal HIV treatment and preventing HIV reduce the number of ICC cases by 2.5 and 6 times, respectively. Conclusions: Optimal treatment and care of HIV patients are essential to reduce their prevalence of ICC, as are preventive strategies which include HPV vaccination, cervical cancer screening strategies and treatment of HSIL. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine whether HIV infection was independently associated with frailty status and its individual components. Methods: This cross‐sectional investigation included people living with HIV (PLWH) and HIV‐negative individuals from the baseline survey of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, China. Frailty phenotype was based on five components: weight loss, low physical activity, exhaustion, weak grip strength and slow gait speed. Frailty was defined as the presence of at least three components, and prefrailty was defined as one or two components. Logistic regression models were used to analyse the factors associated with frailty and its components. Results: In all, 2475 people living with HIV (age 45.5 ± 14.9 years; 76.2% male) and 4948 HIV‐negative individuals (age 45.5 ± 14.8 years; 76.3% male) were included. Among PLWH, median CD4 count was 395 cells/μL and 78% were currently on antiretroviral therapy (ART). Frailty and prefrailty were significantly more prevalent in PLWH (3.2% vs 1.9% and 32.9% vs 27.9%) overall and at ages 18–39 (1.4% vs 0.2% and 22.7% vs 19.0%), 40–59 (2.5% vs 0.9% and 30.9% vs 27.9%) and 60–90 years (8.4% vs 7.4% and 57.1% vs 45.8%). HIV infection was associated with frailty and prefrailty [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.06–2.08; and aOR = 1.18, 95% CI: 1.05–1.33, respectively] after adjusting for confounding variables, but were strengthened with further adjustment for multimorbidity (aOR = 1.62, 95% CI: 1.14–2.28; and aOR = 1.22, 95% CI: 1.09–1.37), and were no longer significant with further adjustment for depressive symptoms and sleep disorders (aOR = 1.02, 95% CI: 0.71–1.46; and aOR = 1.06, 95% CI: 0.94–1.20). Among individual components, HIV infection was positively associated with weak grip strength and slow gait speed, but negatively associated with low physical activity and exhaustion in all the adjusted models described. Conclusions: Frailty and prefrailty occur more often and earlier in PLWH. However, grip strength and gait speed are affected to a greater extent, highlighting their potential as screening and intervention targets to prevent or slow frailty among PLWH. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, a reduction in the life expectancy gap between people living with HIV (PLWH) and the general population has been observed, irrespective of CD4 lymphocyte count, due to widespread access to antiretroviral treatment. The increase in the life expectancy of PLWH has increased awareness of both the ageing process and gender discrepancies in immune restoration and survival. Materials and Methods: Longitudinal data were collected for 2240 patients followed up at the Hospital for Infectious Diseases in Warsaw, Poland (n = 1482), and the Department of Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland (n = 758). Immune restoration was measured from the time of starting combination antiretroviral therapy until achieving 500 CD4 lymphocytes/μL, 800 CD4 lymphocytes/μL, and CD4/CD8 lymphocyte ratios of > 0.8 and > 1.0. Full recovery was achieved when the patient was restored to both 800 CD4 lymphocytes/μL and a CD4/CD8 lymphocyte ratio > 1.0. Results: For all endpoints, immune restoration had a protective effect by reducing mortality. Patients who achieved immune restoration had a greater chance of reduced mortality than those who did not achieve immune restoration: for CD4 count > 500 cells/μL, HR = 5.4 (interquartile range: 3.09–9.41), p < 0.001; for CD4 > 800 cells/μL, HR = 5.37 (2.52–11.43), p < 0.001; for CD4/CD8 ratio > 0.8, HR = 3.16 (1.81–5.51), p < 0.001; for CD4/CD8 ratio > 1.0, HR = 2.67 (1.49–5.24), p = 0.001, and for full immune recovery, HR = 3.62 (1.63–8.04), p = 0.002. Conclusions: Immune restoration remains a powerful factor in improving the survival of PLWH, regardless of the speed of recovery. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to analyse patients newly diagnosed with HIV who were originally admitted to hospitals with suspicion of COVID‐19. Methods: This was a retrospective case series undertaken at four sites. Only adults with new HIV diagnosis and COVID‐19 exclusion hospitalized in 2020–2021 were included. Demographic, clinical and laboratory data were collected from medical records. Results: Twenty‐five patients were included in the analysis: 19 men (76%), 11 of Ukrainian origin (44%). The median age was 38.5 years (range 25–59). The mode of HIV transmission was heterosexual for 11 (44%) patients, eight (32%) were men who have sex with men and three (12%) were people who inject drugs. The median duration of symptoms prior to hospital presentation was 20.6 days (range 3–90). The median number of SARS‐CoV‐2 tests per patient was 2.62 (range 1–7). All SARS‐CoV‐2 tests were negative. Screening for HIV was performed on average on the 18th day of hospitalization (range 1–36 days). Twenty‐three patients (92%) were late presenters, 22 (88%) had advanced disease, and 19 (76%) were in the AIDS stage. The median CD4 T‐cell count was 72 cells/μL (range 3–382). The rate of positive HIV testing at the two sites where it was available for people with suspected COVID‐19 was 0.13% (7/5458 during the study period). Conclusions: We strongly recommend introducing the HIV screening test in the diagnostic algorithm for every patient suspected of having COVID‐19, presenting with clinical and/or radiological pulmonary symptoms. [ABSTRACT FROM AUTHOR]

Background: We investigated the effect of HIV on COVID‐19 outcomes with attention to selection bias due to differential testing and comorbidity burden. Methods: This was a retrospective cohort analysis using four hierarchical outcomes: positive SARS‐CoV‐2 test, COVID‐19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate‐adjusted, inverse probability‐weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV‐IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis. Results: Between March and November 2020, 63 319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS‐CoV‐2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV‐IPW [95% confidence interval (CI): 1.6–2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID‐19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR) = 0.5, 95% CI: 0.1–1.4]. PWH did not have a different rate of ICU admission (aIRR = 1.08, 95% CI: 0.31–3.80) or of in‐hospital death (aIRR = 0.92, 95% CI: 0.08–10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. Conclusions: People living with HIV have a higher risk of COVID‐19 diagnosis than those without HIV but the outcomes are similar in both groups. [ABSTRACT FROM AUTHOR]

Introduction: People who inject drugs are at high risk of blood‐borne infections. We describe the epidemiology of HIV among people who inject drugs in England, Wales, and Northern Ireland (EW&NI) since 1981. Methods: National HIV surveillance data were used to describe trends in diagnoses (1981–2019), prevalence (1990–2019), and behaviours (1990–2019) among people who inject drugs aged ≥15 years in EW&NI. HIV care and treatment uptake were assessed among those attending in 2019. Results: Over the past four decades, the prevalence of HIV among people who inject drugs in EW&NI remained low (range: 0.64%–1.81%). Overall, 4978 people who inject drugs were diagnosed with HIV (3.2% of cases). Diagnoses peaked at 234 in 1987, decreasing to 78 in 2019; the majority were among white men born in the UK/Europe (90%), though the epidemic diversified over time. Late diagnosis (CD4 <350 cells/µl) was common (2010–2019: 52% [429/832]). Of those who last attended for HIV care in 2019, 97% (1503/1550) were receiving HIV treatment and 90% (1375/1520) had a suppressed viral load (<200 copies/ml). HIV testing uptake has steadily increased among people who inject drugs (32% since 1990). However, in 2019, 18% (246/1404) of those currently injecting reported never testing. The proportion of people currently injecting reporting sharing needles/syringes decreased from 1999 to 2012, before increasing to 20% (288/1426) in 2019, with sharing of any injecting equipment at 37% (523/1429). Conclusion: The HIV epidemic among people who inject drugs in EW&NI has remained relatively contained compared with in other countries, most likely because of the prompt implementation of an effective national harm reduction programme. However, risk behaviours and varied access to preventive interventions among people who inject drugs indicate the potential for HIV outbreaks. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical profile and outcome of patients with HIV‐associated plasmablastic lymphoma (PBL) treated with cyclophosphamide, doxorubicin, oncovin, prednisone (CHOP) chemotherapy in a tertiary hospital in KwaZulu‐Natal, South Africa. Methods: This 12‐year retrospective clinical chart review, from 2006 to 2018, of patients with PBL treated with CHOP chemotherapy describes their clinical presentation, complete response (CR), progression‐free survival (PFS) and disease‐free survival (DFS). Response to salvage chemotherapy was also assessed, as was the overall survival (OS). Results: Of 26 patients included in the study, PBL was the presenting manifestation of underlying HIV infection in 58% (n = 15). The median age was 35 years (range 13–49), and 62% (n = 16) were males. The median CD4 count was 285 cells/µL (range 45–863). All patients had extranodal disease, with 4% having bone marrow involvement (n = 1) and > 60% presenting with advanced stage and high‐risk PBL. Central nervous system (CNS) involvement was present in 15% (n = 4). A CR was attained in 46% (n = 12). The median DFS was 23.5 months (range 5–91 months), with an overall 2‐year survival of 42% (n = 11). Conclusions: Patients with PBL had a low CR with CHOP chemotherapy and poor OS. Use of alternative chemotherapy regimens needs to be investigated to optimally manage this aggressive lymphoma. The surprisingly low incidence of marrow involvement is the focus of ongoing local research. [ABSTRACT FROM AUTHOR]

Objectives: Effective and safe COVID‐19 vaccines have been developed and have resulted in decreased incidence and severity of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and can decrease secondary transmission. However, there are concerns about dampened immune responses to COVID‐19 vaccination among immunocompromised patients, including people living with HIV (PLWH), which may blunt the vaccine's efficacy and durability of protection. This study aimed to assess the qualitative SARS‐CoV‐2 vaccine immunogenicity among PLWH after vaccination. Methods: We conducted targeted COVID‐19 vaccination (all received BNT162b2 vaccine) of PLWH (aged ≥ 55 years per state guidelines) at Yale New Haven Health System and established a longitudinal survey to assess their qualitative antibody responses at 3 weeks after the first vaccination (and prior to receipt of the second dose of the COVID‐19 vaccine) (visit 1) and at 2–3 weeks after the second vaccination (visit 2) but excluded patients with prior COVID‐19 infection. Our goal was to assess vaccine‐induced immunity in the population we studied. Qualitative immunogenicity testing was performed using Healgen COVID‐19 anti‐Spike IgG/IgM rapid testing. Poisson regression with robust standard errors was used to determine factors associated with a positive IgG response. Results: At visit 1, 45 of 78 subjects (57.7%) tested positive for SARS‐CoV‐2 anti‐Spike IgG after the first dose of COVID‐19 vaccine. Thirty‐nine subjects returned for visit 2. Of these, 38 had positive IgG (97.5%), including 20 of 21 subjects (95.2%) with an initial negative anti‐Spike IgG. Our bivariate analysis suggested that participants on an antiretroviral regimen containing integrase strand transfer inhibitors [relative risk (RR) = 1.81, 95% confidence interval (CI): 0.92–3.56, p = 0.085] were more likely to seroconvert after the first dose of the COVID‐19 vaccine, while those with a CD4 count < 500 cells/μL (RR = 0.59, 95% CI: 0.33–1.05, p = 0.071), and those diagnosed with cancer or another immunosuppressive condition (RR = 0.49, 95% CI: 0.18–1.28, p = 0.15) may have been less likely to seroconvert after the first dose of the COVID‐19 vaccine. The direction of these associations was similar in the multivariate model, although none of these findings reached statistical significance (RRintegrase inhibitor = 1.71, 95% CI: 0.90–3.25, p = 0.10; RRCD4 count = 0.68, 95% CI: 0.39–1.19, p = 0.18; RRcancer or another immunosuppressive condition = 0.50, 95% CI: 0.19–1.33, p = 0.16). With regard to immunogenicity, we were able to record very high rates of new seroconversion following the second dose of the COVID‐19 vaccine. Conclusions: Our study suggests that completing a two‐dose series of BNT162b2 vaccine is critical for PLWH given suboptimal seroconversion rates after the first dose and subsequent improved seroconversion rates after the second dose. [ABSTRACT FROM AUTHOR]

Background: There is currently little evidence exploring menopausal status, age at last menstrual period (LMP) and management of menopause among women living with HIV aged 45–60 years in England. Methods: Socio‐demographic, lifestyle and clinical data were collected through a self‐completed cross‐sectional survey. Longitudinal CD4 count and viral load data were available from linkage to clinical records, if consent was provided. Women were categorised as pre‐, peri‐ or post‐menopausal. Factors associated with menopausal stage were examined using ordinal logistic regression adjusting for age. Age at LMP was estimated using Kaplan–Meier survival analysis. Results: The 847 women had a median age of 49 [interquartile range (IQR): 47–52] years. Most were of black ethnicity (81.3%), were born outside the UK (85.0%) and had completed secondary education (88.7%); 177 (20.4%), 373 (43.0%) and 297 (34.2%) were pre‐, peri‐ or post‐menopausal, respectively. After adjusting for age, associations of menopausal status with non‐cohabiting relationship [adjusted odds ratio = 0.63 (95% confidence interval: 0.43–0.91)], baseline viral load ≥ 100 000 copies/mL [2.67 (1.20–5.94)] and unemployment [1.34 (0.97–1.84)] remained significant. Median (IQR) age at LMP was 54 (51–55) years in the group. In total, 27.9% (233/836) of women reported severe menopausal symptoms; 45.6% of those with somatic symptoms had heard of hormone replacement therapy and 8.7% had used it. Only 5.6% of women with urogenital symptoms had used topical oestrogen. Conclusions: Our findings highlight the importance of educating both women and their healthcare providers about menopausal symptoms and management options. [ABSTRACT FROM AUTHOR]

Objectives: Plasmablastic lymphoma (PBL) is a clinically aggressive lymphoma which has a predilection for extranodal sites and is frequently HIV‐associated. The incidence of non‐Hodgkin lymphoma is thought to be reduced by widescale antiretroviral therapy (ART) coverage, but the literature is sparse as regards the impact of ART on the incidence of PBL and its outcomes in South Africa (SA). This study aimed to compare factors of interest in cases of PBL diagnosed before and after the widespread availability of ART in Johannesburg, SA. Methods: All cases of PBL diagnosed in the state sector hospitals of Johannesburg in 2007 and 2017 (before and after the widespread availability of ART, respectively) were extracted from the laboratory information system, and factors of interest compared. Results: The majority (> 95%) of cases of PBL were seen among people with HIV infection (PWH) at both time‐points, and the proportion of patients on ART and with virological suppression (VS) increased significantly in 2017. However, the number of cases of PBL did not differ significantly between the two years assessed, comprising 46/397 (11.6%) and 53/582 (9.6%) of all lymphomas in 2007 and 2017, respectively (P = 0.23). Ongoing risk for PBL among PWH with virological control and immunological recovery was evident in 2017, as 18.9% of the patients had both VS and CD4 counts > 200 cells/μL at diagnosis. Inferior survival times were associated with elevated lactate dehydrogenase (LDH) levels and Epstein Barr virus (EBV) negativity, but were not influenced by the presence of AIDS, ART or VS. EBV negativity was significantly associated with VS, and appeared to flag a particularly aggressive form of the disease. Conclusions: Widescale ART coverage has not reduced the incidence of PBL in Johannesburg, and an ongoing risk for this disease among PWH with adequate virological control and immunological recovery persists. [ABSTRACT FROM AUTHOR]

Objectives: A risk score for long‐term prediction of chronic kidney disease (CKD) in people living with HIV (PLHIV) has been developed using data from the D:A:D cohort. We assessed the performance of the D:A:D risk score in a cohort of PLHIV in West Africa. Methods: Data from PLHIV starting antiretroviral treatment in four clinics in Burkina Faso, Côte d'Ivoire and Togo participating in the IeDEA West Africa collaboration were analysed. CKD was defined as two consecutive estimated glomerular filtration rates (eGFRs) of ≤ 60 mL/min/1.73 m2. The D:A:D score (short version) was calculated using age, gender, nadir CD4 and baseline eGFR and was categorized into low, medium, and high‐risk groups. Results: In 14 930 participants (70% female, median age = 38 years; median nadir CD4 count = 183 cells/µL) followed for a median duration of 5.7 years, 660 (4.4%) progressed to CKD, with an incidence [95% confidence interval (CI)] of 7.8 (7.2–8.4) per 1000 person‐years (PY). CKD incidence rates were 2.4 (2.0–2.8), 8.1 (6.8–9.6) and, 30.9 (28.0–34.1) per 1000 PY in the low‐, medium‐ and high‐risk groups, respectively. In the high‐risk group, 14.7% (95% CI: 13.3; 16.3) had progressed to CKD at 5 years. Discrimination was good [C‐statistics = 0.81 (0.79–0.83)]. In all, 79.4% of people who progressed to CKD were classified in the medium‐ to high‐risk group at baseline (sensitivity) and 66.5% of people classified in the low risk group at baseline did not progress to CKD (specificity). Conclusions: These findings confirm the validity of the D:A:D score in identifying individuals at risk of developing CKD who could benefit from enhanced kidney monitoring in West African HIV clinics. [ABSTRACT FROM AUTHOR]

Objectives: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). Methods: We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual‐energy X‐ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. Results: In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479–800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new‐onset metabolic syndrome. Conclusions: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004–2017. Methods: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models. Results: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL. Conclusions: The initial assessment of HIV‐infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations. [ABSTRACT FROM AUTHOR]

Objectives: In terms of HIV infection, western and central Africa is the second most affected region world‐wide, and the gap between the regional figures for the testing and treatment cascade and the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90–90–90 targets is particularly worrying. We assessed the prevalence of virological suppression in patients routinely treated in 19 hospitals in Cameroon. Methods: A cross‐sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in the Centre and Littoral regions. The prevalences of virological suppression (<1000 HIV‐1 RNA copies/mL) were compared among all 19 hospitals using the χ2 test. Potential individual and health care‐related determinants of virological suppression were assessed using multivariate logistic regression models. Results: A total of 1700 patients (74% women; median age 41 years; median time on ART 3.7 years) were included in the study. The prevalence of virological suppression was 82.4% overall (95% confidence interval 80.5–84.2%). It ranged from 57.1 to 97.4% according to the individual hospital (P < 0.001). After adjustment, virological suppression was associated with age, CD4 cell count at ART initiation, disclosure of HIV status to family members, interruption of ART for more than two consecutive days, and location of patient's residence and hospital (rural/urban). These factors did not explain the heterogeneity of virological suppression between the study hospitals (P < 0.001). Conclusions: The overall prevalence of virological suppression was reassuring. Nevertheless, the heterogeneity of virological suppression among hospitals highlights that, in addition to programme‐level data, health facility‐level data are crucial in order to tailor the national AIDS programme's interventions with a view to achieving the third UNAIDS 90 target. [ABSTRACT FROM AUTHOR]

Objectives: In adults with horizontally acquired HIV infection, an inverted CD4:CD8 ratio is associated with persistent immune activation, size of HIV reservoir and predicts an increased risk of non‐AIDS‐defining adverse events. Normalization of this ratio with antiretroviral therapy (ART) is suboptimal in adults, despite viral suppression, and is less well described in paediatric populations. We investigated rates of CD4:CD8 ratio recovery in children with perinatally acquired HIV infection (PaHIV) on ART. Methods: A cross‐sectional, retrospective analysis of routine clinical data in children with PaHIV (5–18 years old) attending a single UK centre was carried out. Results: CD4:CD8 normalization was seen in 62% of children on suppressive ART. A negative correlation was found between current CD4:CD8 ratio and age at start of ART. Positive correlations were found between current CD4:CD8 ratio and total time with suppressed HIV viral load and nadir CD4 counts. Multiple linear regression analysis showed that age at start of ART was significantly associated with current CD4:CD8 ratio (standardized β = −0.680; P < 0.001). Patient sex, ethnicity and antiretroviral regimen did not affect ratio recovery. Conclusions: We found higher rates of CD4:CD8 ratio normalization compared with previous adult studies. Children who started ART at a younger age were more likely to recover a normal ratio. The current policy of universal treatment for all HIV‐positive adults and children will enhance immunological normalization. [ABSTRACT FROM AUTHOR]

Objectives: India has the highest number of HIV‐infected adolescents in Asia, but little is known about their treatment outcomes. We assessed rates and factors associated with loss to follow‐up (LTFU) and mortality among Indian adolescents. Methods: The analysis included adolescents (10–19 years old) starting antiretroviral therapy (ART) between 2005 and 2014 at BJ Government Medical College, Pune, India. LTFU was defined as missing more than three consecutive monthly visits. The competing‐risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for LTFU, with death as the competing risk. Cox proportional hazard models were used to identify predictors of mortality. Results: Of 717 adolescents starting ART, 402 with complete data were included in the analysis. Of these, 61% were male and 80% were perinatally infected, and the median baseline CD4 count was 174 cells/μL. LTFU and mortality rates were 4.4 and 4.9/100‐person years, respectively. Cumulative LTFU incidence increased from 6% to 15% over 6 years. Age ≥ 15 years [adjusted SHR (aSHR) 2.44; 95% confidence interval (CI) 1.18–5.02] was a risk factor for LTFU. Cumulative mortality increased from 9.5% to 17.9% over 6 years. World Health Organization (WHO) stages III and IV [adjusted hazard ratio (aHR) 2.26; 95% CI: 1.14–4.48] and an increase in CD4 count by 100 cells/μL (aHR: 0.59; 95% CI: 0.43–0.83) were associated with mortality. Conclusions: A third of adolescents had been lost to follow‐up or died by follow‐up year 6. Older age was a risk factor for LTFU and advanced clinical disease for death. Strategies to improve retention counselling for older adolescents and closer clinical monitoring of all adolescents must be considered. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to evaluate differences in immunovirological response to combination antiretroviral therapy ( cART) in migrant and native men and women within a European collaboration of HIV cohorts Collaboration of Observational HIV Epidemiological Research in Europ ( COHERE) in EuroCoord, 2004-2013. Methods Migrants were defined as those with geographical origin ( GO) different from the reporting country and were grouped as originating from Western Europe and Western Countries ( WEWC), Eastern Europe ( EE), North Africa and the Middle East ( NAME), sub-Saharan Africa ( SSA), Latin America ( LA), Caribbean ( CRB) and Asia/Oceania ( ASIA/ OCE). Native ( NAT) individuals were defined as those originating from the reporting country. CD4 cell counts were modelled using piecewise linear mixed-effects models with two slopes, whereas models to estimate subdistribution hazard ratios ( sHRs) were used for time to virological response ( VR) (i.e. time from cART initiation to the first of two successive HIV RNA measurements < 400 HIV-1 RNA copies/ ml). Results Of 32 817 individuals, 25 799 (78.6%) were men. The percentage of migrants was higher in women (48.9%) than in men (21.2%) and migrants from SSA accounted for the largest migrant group (29.9% in men and 63.3% in women). Migrant men and women from SSA started at lower CD4 cell counts than NAT individuals, which remained lower over time. VR was ≥ 85% at 12 months for all groups except CRB women (77.7%). Compared with NAT men and women, lower VR was experienced by NAME [ sHR 0.91; 95% confidence interval ( CI) 0.86-0.97] and SSA ( sHR 0.88; 95% CI 0.82-0.95) men and CRB ( sHR 0.77; 85% CI 0.67-0.89) women, respectively. Conclusions Immunovirological response to cART in Western Europe varies by GO and sex of patients. ART benefits are not equal for all, underlining the point that efforts need to prioritize those most in need. [ABSTRACT FROM AUTHOR]

Objectives The number of HIV-infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non-travelers. Methods Swiss HIV Cohort Study participants with at least one follow-up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV-1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound. Results We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers [less advanced Centers for Disease Control and Prevention ( CDC) stage and higher CD4 count nadir]. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes [unadjusted odds ratio ( OR) 0.87; 95% confidence interval ( CI) 0.78-0.97]. Among these 477 post-travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian ( OR 0.67; 95% CI 0.51-0.88) and higher in sub-Saharan African ( SSA) patients ( OR 1.41; 95% CI 1.22-1.62). Travel further increased the odds of viral rebound in SSA patients ( OR 2.00; 95% CI 1.53-2.61). Conclusions Region of origin is the main risk factor for viral rebound rather than travel per se. Pre-travel adherence counselling should focus on patients of SSA origin. [ABSTRACT FROM AUTHOR]

Objectives HIV-infected adults have heightened monocyte activation and inflammation, at least partially as a consequence of altered gut integrity. The role of dietary factors in microbial translocation and inflammation and their downstream effect on markers of cardiovascular disease (CVD) have not been explored. Our purpose was to describe the longitudinal dietary patterns of HIV-infected adults, and to examine the relationship between dietary intake, gut integrity, inflammation and subclinical markers of CVD in HIV-infected adults. Methods We conducted a secondary analysis of 147 HIV-infected participants in a 96-week randomized clinical trial of rosuvastatin as primary CVD prevention. Dietary intake was assessed using dietary recall; plasma gut integrity, monocyte activation and inflammation markers were measured using an enzyme-linked immunosorbent assay ( ELISA); and CVD risk was assessed using carotid ultrasound and the coronary artery calcium score. Linear mixed models were used to analyse longitudinally measured biomarkers. Results The median age was 45 years and 78% of patients were male. At baseline, participants consumed a mean (standard deviation) of 108 (70) g of fat daily, 19 (15.6) g of fibre, 266 (186) g of carbohydrates and 15.6 (5.9) g of protein; 45% of the sample consumed alcohol. Over time, alcohol consumption was associated with several markers of gut integrity and inflammation (all P < 0.05). Conclusions HIV-infected adults in a contemporary, high-resource setting have poor dietary patterns. Alcohol use was associated with worse gut integrity and increased inflammation, while other aspects of diet (fibre, carbohydrates and fat) were not. These data add to growing evidence illustrating the need for a better understanding of the effect of lifestyle factors on comorbidities in HIV-infected adults. [ABSTRACT FROM AUTHOR]

Objectives Involvement of people living with HIV ( PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research. Methods PLHIV were recruited in June−November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption ( TI). We examined factors associated with TI and willingness to accept substantial risks. Results A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men ( MSM). Fifty-one per cent were aged 25-44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range ( IQR) 2-17 years]. Eighty-eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV-negative (69%). Ninety-five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201-350 cells/ μL vs. ≥ 350 cells/ μL; odds ratio ( OR) 2.11; 95% confidence interval ( CI) 1.11-4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45-64 years were less likely to accept risks [ OR 0.58 (95% CI 0.37-0.90) and OR 0.18 (95% CI 0.07-0.45), respectively]. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%). Conclusions Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk. [ABSTRACT FROM AUTHOR]

Objectives The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy ( cART) in HIV-1-infected patients. Methods All patients in the Collaboration of Observational HIV Epidemiological Research Europe ( COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/ mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. Results A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range ( IQR) 150, 336] cells/ μL. The median observed CD4 counts at 6, 9 and 12 months were 382 ( IQR 256, 515), 402 ( IQR 274, 543) and 420 ( IQR 293, 565) cells/ μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/ mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. Conclusions Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control. [ABSTRACT FROM AUTHOR]

Objective To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors ( NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy. Methods Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz ( EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir ( LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed. Results Thirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm. Conclusions Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance. [ABSTRACT FROM AUTHOR]

Objectives Adipose tissue affects several aspects of the cellular immune system, but prior epidemiological studies have differed on whether a higher body mass index ( BMI) promotes CD4 T-cell recovery on antiretroviral therapy ( ART). The objective of this analysis was to assess the relationship between BMI at ART initiation and early changes in CD4 T-cell count. Methods We used the North American AIDS Cohort Collaboration on Research and Design ( NA- ACCORD) data set to analyse the relationship between pre-treatment BMI and 12-month CD4 T-cell recovery among adults who started ART between 1998 and 2010 and maintained HIV-1 RNA levels < 400 copies/mL for at least 6 months. Multivariable regression models were adjusted for age, race, sex, baseline CD4 count and HIV RNA level, year of ART initiation, ART regimen and clinical site. Results A total of 8381 participants from 13 cohorts contributed data; 85% were male, 52% were nonwhite, 32% were overweight ( BMI 25-29.9 kg/m2) and 15% were obese ( BMI > 30 kg/m2). Pretreatment BMI was associated with 12-month CD4 T-cell change ( P < 0.001), but the relationship was nonlinear ( P < 0.001). Compared with a reference of 22 kg/m2, a BMI of 30 kg/m2 was associated with a 36 cells/μL [95% confidence interval ( CI) 14, 59 cells/μL] greater CD4 T-cell count recovery among women and a 19 cells/μL (95% CI 9, 30 cells/μL) greater recovery among men at 12 months. At a BMI > 30 kg/m2, the observed benefit was attenuated among men to a greater degree than among women, although this difference was not statistically significant. Conclusions A BMI of approximately 30 kg/m2 at ART initiation was associated with greater CD4 T-cell recovery at 12 months compared with higher or lower BMI values, suggesting that body composition may affect peripheral CD4 T-cell recovery. [ABSTRACT FROM AUTHOR]

Objectives Certain non- AIDS-related diseases have been associated with immunodeficiency and HIV RNA levels in HIV-infected patients on combination antiretroviral therapy ( cART). We aimed to investigate these associations in patients not yet on cART, when potential antiretroviral-drug-related effects are absent and variation in RNA levels is greater. Methods Associations between, on the one hand, time-updated CD4 counts and plasma HIV RNA and, on the other hand, a composite non- AIDS-related endpoint, including major cardiovascular diseases, liver fibrosis/cirrhosis, and non- AIDS-related malignancies, were studied with multivariate Poisson regression models in 12 800 patients diagnosed with HIV infection from 1998 onwards while not yet treated with cART. Results During 18 646 person-years of follow-up, 203 non- AIDS-related events occurred. Compared with a CD4 count ≥ 500 cells/μL, adjusted relative risks ( RRs) for the composite endpoint were 4.71 [95% confidence interval ( CI) 2.98-7.45] for a CD4 count < 200 cells/μL, 2.06 (95% CI 1.38-3.06) for a CD4 count of 200-349 cells/μL, and 1.19 (95% CI 0.82-1.74) for a CD4 count of 350-499 cells/μL. There was no evidence for an independent association with HIV RNA. Other important covariates were age [ RR 1.40 (95% CI 1.31-1.49) per 5 years older], hepatitis B virus coinfection [ RR 5.66 (95% CI 3.87-8.28)] and hepatitis C virus coinfection [ RR 9.26 (95% CI 6.04-14.2)]. Conclusions In persons not yet receiving cART, a more severe degree of immunodeficiency rather than higher HIV RNA levels appears to be associated with an increased risk of our composite non- AIDS-related endpoint. Larger studies are needed to address these associations for individual non- AIDS-related events. [ABSTRACT FROM AUTHOR]

The author reflects on the Strategies for Management of AntiRetroviral Therapy (SMART) study, which examines the benefits and risks of ART in HIV treatment. Issues investigated in the study are discussed including existence of causal link between inflammation and cardiovascular disease, whether ART should be initiated early or after the HIV has impaired the immune system and the risks of AIDS.

Objectives The risks and benefits of initiating antiretroviral treatment ( ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment ( START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/μL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. Methods Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. Results START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range ( IQR) 29-44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year ( IQR 0.4-3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/μL ( IQR 584-765 cells/μL) and 12 754 HIV RNA copies/mL ( IQR 3014-43 607 copies/mL), respectively. Conclusions START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes. [ABSTRACT FROM AUTHOR]

Objectives Viral load ( VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief ( PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. Methods In this cross-sectional, observational study, patients on first-line antiretroviral therapy ( ART) (efavirenz or nevirapine + zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load ( HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or > 24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. Results We found that 85.2% of 325 subjects were virologically suppressed (viral load < 47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/μL, respectively; P < 0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio ( OR) 0.47; 95% confidence interval ( CI) 0.22-1.02; P = 0.057], lower cost of clinic visits ( OR 0.815; 95% CI 0.66-1.00; P = 0.05), improvement in CD4 percentage ( OR 1.06; 95% CI 1.014-1.107; P = 0.009), and care at Kayunga vs. Kangulamira ( OR 0.47; 95% CI 0.23-0.92; P = 0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy ( ART) ( P < 0.0001), patient satisfaction with care ( P = 0.038), improvements in total lymphocyte count ( P < 0.0001) and haemoglobin concentration ( P = 0.05) were positively associated, whereas age at start of ART ( P = 0.0045) was negatively associated with this outcome. Conclusions High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age. [ABSTRACT FROM AUTHOR]

Objectives Late presentation to HIV/ AIDS services compromises treatment outcomes and misses opportunities for biomedical and behavioural prevention. There has been significant heterogeneity in how the term 'late presentation' ( LP) has been used in the literature. In 2011, a consensus definition was reached using CD4 counts to define and measure late presenters and, while it is useful for clinical care, the consensus definition has several important limitations that we discuss in this article. Methods Using the spectrum of engagement in HIV care presented by Gardner and colleagues, this article highlights issues and opportunities associated with use of the consensus definition. Results The consensus definition is limited by three principal factors: (1) the CD4 count threshold of 350 cells/μ L is being increasingly questioned as the biomedical justification grows for earlier initiation of treatment; (2) CD4 evaluations are conducted at multiple services providing HIV care; thus it remains unclear to which service the patient is presenting late; and (3) the limited availability of CD4 evaluation restricts its use in determining the prevalence of LP in many settings. Conclusions The consensus definition is useful because it describes the level of disease progression and allows for consistent evaluation of the prevalence and determinants of LP. Suggestions are provided for improving the application of the consensus definition in future research. [ABSTRACT FROM AUTHOR]

Objectives Although combination antiretroviral therapy ( cART) can restore CD4 T-cell numbers in HIV infection, alterations in T-cell regulation and homeostasis persist. We assessed the incidence and predictors of reversing these alterations with cART. Methods ART-naïve adults (n = 4459) followed within the Canadian Observational Cohort and exhibiting an abnormal T-cell phenotype ( TCP) prior to cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T-cell count (< 532 cells/μ L), (2) lost T-cell homeostasis ( CD3 < 65% or > 85%) or (3) CD4: CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP, CD4 and CD8 T-cell percentages and absolute counts were also analysed for a median duration of 3.14 years [interquartile range ( IQR) 1.48-5.47 years]. Predictors of TCP normalization were assessed using adjusted Cox proportional hazards models. Results At baseline, 96% of pateints had CD4 depletion, 32% had lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third of patients had normalized CD4 T-cell counts, but only 85 individuals (2%) had normalized their TCP. In a multivariable model adjusted for age, measurement frequency and baseline regimen, higher baseline CD4 T-cell counts and time-dependent viral suppression independently predicted TCP normalization [hazard ratio ( HR) for baseline CD4 T-cell count = 1.42 (1.31-1.54) per 100 cells/μ L increase; P ≤ 0.0001; HR for time-dependent suppressed viral load = 3.69 (1.58-8.61); P-value ≤ 0.01]. Conclusions Despite effective cART, complete TCP recovery occurred in very few individuals and was associated with baseline CD4 T-cell count and viral load suppression. HIV-induced alterations of the TCP are incompletely reversed by long-term ART. [ABSTRACT FROM AUTHOR]

Objectives Recent studies have reported faster progression of HIV infection than anticipated based on results from earlier studies. The aim of the present study was to examine if the virulence of HIV-1 infection changed in the period 1995-2010 among chronically HIV-infected individuals in Denmark. Methods We included all patients registered in the Danish HIV Cohort Study, who were diagnosed in 1995-2009, had a CD4 count > 100 cells/μL at diagnosis and had at least two CD4 measurements prior to initiation of antiretroviral therapy ( ART). Changes in viral set point and rate of CD4 cell decline from enrolment until the initiation of ART by calendar year of HIV diagnosis were analysed. Time to first CD4 count < 350 cells/μL was compared among patients diagnosed in 1995-2000, 2001-2005 and 2006-2010. Results We followed 1469 HIV-infected patients for a total of 5783 person-years. The median viral set point was 4.27 log10 HIV-1 RNA copies/mL [interquartile range ( IQR) 3.58-4.73 log10 copies/mL]. The median CD4 cell decline per year was 57 cells/μL ( IQR 10-139 cells/μL). In analyses adjusted for age, gender, origin, route of transmission and CD4 count at diagnosis, there were no associations between year of diagnosis and viral set point or CD4 cell decline. Time to first CD4 count < 350 cells/μL did not change in the study period [incidence rate ratio ( IRR) 0.90 (95% confidence interval ( CI) 0.76-1.06) for 2001-2005 and 1.09 (95% CI 0.79-1.34) for 2006-2010 compared with 1995-2000]. Conclusions We found no evidence of changing trends in viral set point, CD4 cell decline or time to CD4 count < 350 cells/μL during the period 1995-2010 in a cohort of chronically HIV-infected individuals. [ABSTRACT FROM AUTHOR]

The article discusses the recommendations with regards to the use of antiretroviral therapy (ART) in pregnancy. Women conceiving on an effective HAART regimen should continue ART even if it contains efavirenz or does not contain zidovudine and conditions under which exceptions are there are included. The Antiretroviral Pregnancy Registry (APR) provides the best data on teratogenicity and first trimester ART exposure. The Writing Group recommends that efavirenz can be used during pregnancy.

Objectives Despite the rise of methicillin-resistant Staphylococcus aureus ( MRSA) skin and soft tissue infections ( SSTIs) among HIV-infected persons during the era of highly active antiretroviral therapy ( HAART), the precise relationship between these two infections has not been fully elucidated. Therefore, we provide a comprehensive, literature-based review of MRSA infections among HIV-infected persons. Methods A systematic search of MEDLINE using the search terms ' HIV' and ' MRSA' identified references published during the HAART era ( January 1996 to January 2011). Relevant articles on MRSA in the general population were also reviewed for comparison. Results The most common type of MRSA infection among HIV-infected persons is SSTI caused by USA300, Panton-Valentine leukocidin ( PVL)-positive strains. HIV-infected persons have an increased risk for both initial MRSA infections and recurrent infections compared with the general population. Risk factors for MRSA infections in this population include immunosuppression, comorbid conditions and certain lifestyle behaviours such as high-risk sexual behaviours and illicit drug use. Further research is needed on the optimal treatment and prevention strategies for MRSA infections among HIV-infected persons. Conclusions HIV-infected persons have a propensity for MRSA SSTI and a high rate of recurrent disease. The reasons for the elevated rates of MRSA infections among HIV-infected persons appear to be multifactorial, but may be mitigated with optimized HIV control and reductions in associated risk factors. [ABSTRACT FROM AUTHOR]

The article discusses the cases in which screening is recommended for HIV-positive pregnant women. HIV-positive pregnant women should be managed as per Guidelines for the NHS Cervical Screening Programme 2010. In the case of late-presenting women, HAART, based on epidemiological assessment of resistance, should be initiated without delay and modified once the resistance test is available. Treatment in cases where failure to suppress has taken place is also highlighted.