HIV

Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood.

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.

The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.

There is considerable genetic diversity among viruses of different subtypes (designated A to J) in the major group of human immunodeficiency virus type 1 (HIV-1), the form of HIV that is dominant in the global epidemic. If available, HIV-1 sequences pre-dating the recognition of AIDS could be crucial in defining the time of origin and the subsequent evolution of these viruses in humans. The oldest known case of HIV-1 infection was reported to be that of a sailor from Manchester who died of an AIDS-like illness in 1959; however, the authenticity of this case has not been confirmed. Genetic analysis of sequences from clinical materials obtained from 1971 to 1976 from members of a Norwegian family infected earlier than 1971 showed that they carried viruses of the HIV-1 outlier group, a variant form that is mainly restricted to West Africa. Here we report the amplification and characterization of viral sequences from a 1959 African plasma sample that was previously found to be HIV-1 seropositive. Multiple phylogenetic analyses not only authenticate this case as the oldest known HIV-1 infection, but also place its viral sequence near the ancestral node of subtypes B and D in the major group, indicating that these HIV-1 subtypes, and perhaps all major-group viruses, may have evolved from a single introduction into the African population not long before 1959.

After publication of the original article [1], we were notified in Table 1 a column should be removed.…

Abstract Background Blastocystis is one of the most common intestinal protozoa in human faecal samples with uncertain impact on public health. Studies on the prevalence of Blastocystis in HIV-positive patients are limited and dated. Methods A cross-sectional study was carried out involving 156 HIV-positive patients to evaluate the prevalence of Blastocystis-subtypes by molecular amplification and sequencing the small subunit rRNA gene (SSU rDNA), to identify the risk factors for its transmission, to examine the relationship between the presence of the protist and gastrointestinal disorders. Furthermore, the evaluation of the faecal calprotectin by immunoassay from a sample of subjects was performed to evaluate the gut inflammation in Blastocystis-carriers. Results Blastocystis-subtypes ST1, ST2, ST3, ST4 were identified in 39 HIV-positive patients (25%). No correlation was found between the presence of the protist and virological or epidemiological risk factors. Blastocystis was more frequently detected in homosexual subjects (p = 0.037) infected by other enteric protozoa (p = 0.0001) and with flatulence (p = 0.024). No significant differences in calprotectin level was found between Blastocystis-carriers and free ones. Conclusions Blastocystis is quite common in HIV-positive patients on ART showing in examined patients 25% prevalence. Homosexual behaviour may represent a risk factor for its transmission, while CD4 count and viremia didn’t correlate with the presence of the protist. The pathogenetic role of Blastocystis remains unclear and no gut inflammation status was detected in Blastocystis-carriers. The only symptom associated with Blastocystis was the flatulence, evidencing a link between the presence of the protist and the composition and stability of gut microbiota.…

Davy-Mendez T, Napravnik S, Wohl D, et al.

AbstractBackgroundAdvances in antiretroviral therapy, aging, and comorbidities impact hospitalization rates in HIV-infected populations. We examined temporal trends and patient characteristics associated with hospitalization rates and outcomes.MethodsStudy population included patients in the University of North Carolina Center for AIDS Research HIV Clinical Cohort receiving clinical care 1996–2016. We estimated annual hospitalization rates, time to inpatient mortality or live discharge, and 30-day readmission risk using bivariable Poisson, Fine and Gray, and log-binomial regression models.Results4323 patients (29% women, 60% African-American) contributed 30 007 person-years. Overall, the hospitalization rate per 100 person-years was 34.3 (95% confidence interval [CI] 32.4, 36.4) with a mean change of -3% per year (95% CI -4%, -2%). Thirty-day readmission risk was 18.9% (95% CI 17.7%, 20.2%) and stable over time (P=0.21 and P=0.44 for 2010–2016 and 2003–2009, respectively, compared to 1996–2002). Patients who were Black (compared to White), older, had HIV RNA >400 copies/mL, or had CD4 count

Colasanti J, del Rio C.

Salazar-Austin N, Cohn S, Lala S, et al.

AbstractBackgroundBoth pregnancy and HIV increase the risk of tuberculosis disease which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among HIV-infected individuals in high-burden settings, but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy.MethodsIn this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight and congenital anomaly) in HIV-infected pregnant women enrolled as controls in the Tshepiso study, a prospective observational cohort of HIV-infected pregnant women with and without TB disease in Soweto, South Africa from 2011-2014.ResultsThere were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed participants, 11 (16%) had an adverse pregnancy outcome compared to 23 of 82 (23%) IPT-unexposed participants. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95%CI: 1.0, 6.5; p=0.048) times higher in IPT-unexposed women compared to IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index and anemia.ConclusionsIPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for relevant demographic, clinical and HIV-related factors. These results may provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to confirm both the safety of IPT and new short-course TB preventive therapies during pregnancy.

Abstract Background The therapeutic response of cervical tuberculous lymphadenitis (CTBL) may be delayed or paradoxical, with the frequent development of residual lymph nodes (LNs) during and after antituberculous treatment. We investigated the incidence of residual LNs and the clinical, radiological, microbiological, and pathologic responses of patients with CTBL after 6 months of antituberculous therapy. Methods The medical records of HIV-negative adult patients with CTBL diagnosed between July 2009 and December 2017 were analyzed. After 6 months of first-line antituberculous treatment, computed tomography (CT) scans were conducted to evaluate for residual LNs. Fine-needle aspiration biopsy (FNAB) was carried out if a patient presented with residual LNs > 10 mm in diameter with central necrosis, peripheral rim enhancement, or perinodal inflammation on CT scan. Results Residual LNs were detected in 35 of 157 patients who underwent follow-up CT scans and were more commonly observed in younger patients who completed the treatment (mean years ± standard deviation [SD]: 33 ± 13 vs. 44 ± 16, p 

Aizire, Jim; Sikorskii, Alla; Ogwang, Lillian Wambuzi; Kawalazira, Rachel; Mutebe, Alex; Familiar-Lopez, Itziar; Mallewa, MacPherson; Taha, Taha; Boivin, Michael J.; Fowler, Mary Glenn; for the PROMISE-NEURODEV study team

Objective: To compare growth among antiretroviral drug and maternal-HIV exposed uninfected (AHEU) versus age-and-sex-matched HIV unexposed uninfected (HUU) children. Design: Prospective cohort of AHEU children identified from the PROMISE trial (NCT01061151: clinicaltrials.gov registry) and age-and-sex-matched HUU controls from child-wellness clinics, enrolled (09/2013–10/2014) in Malawi and Uganda. Methods: Weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head-circumference-for-age (HCAZ) z-scores were derived at 12 and 24 months-of-age. Wilcoxon Rank-Sum and Fischer's exact tests were used for unadjusted exposure group comparisons. Generalized-Estimating-Equations models estimated adjusted relative risks (aRR) for poor growth outcomes. Results: Overall, 471 (50.5%) AHEU and 462 (49.5%) HUU children were assessed. Ugandan AHEU compared to HUU children had significantly lower mean LAZ (p …

Koenig S, Kim A, Shepherd B, et al.

AbstractWe assessed association between cured tuberculosis and mortality among persons with HIV in Latin America. We compared survival among persons with and without tuberculosis at enrollment in HIV care, starting 9 months after clinic enrollment. In multivariable analysis, tuberculosis was associated with higher long-term mortality (hazard ratio=1.57; 95% confidence interval=1.25-1.99).

Li, Yuruo; Liu, Hongjie; Ramadhani, Habib O.; Ndembi, Nicaise; Crowell, Trevor A.; Kijak, Gustavo; Robb, Merlin L.; Ake, Julie A.; Kokogho, Afoke; Nowak, Rebecca G.; Gaydos, Charlotte; Baral, Stefan D.; Volz, Erik; Tovanabutra, Sodsai; Charurat, Man; TRUST/RV368 Study Group

Background: The HIV epidemic continues to grow among MSM in countries across sub-Saharan Africa including Nigeria. To inform prevention efforts, we used a phylogenetic cluster method to characterize HIV genetic clusters and factors associated with cluster formation among MSM living with HIV in Nigeria. Methods: We analyzed HIV-1 pol sequences from 417 MSM living with HIV enrolled in the TRUST/RV368 cohort between 2013 and 2017 in Abuja and Lagos, Nigeria. A genetically linked cluster was defined among participants whose sequences had pairwise genetic distance of 1.5% or less. Binary and multinomial logistic regressions were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with HIV genetic cluster membership and size. Results: Among 417 MSM living with HIV, 153 (36.7%) were genetically linked. Participants with higher viral load (AOR = 1.72 95% CI: 1.04–2.86), no female partners (AOR = 3.66; 95% CI: 1.97–6.08), and self-identified as male sex (compared with self-identified as bigender) (AOR = 3.42; 95% CI: 1.08–10.78) had higher odds of being in a genetic cluster. Compared with unlinked participants, MSM who had high school education (AOR = 23.84; 95% CI: 2.66–213.49), were employed (AOR = 3.41; 95% CI: 1.89–10.70), had bacterial sexually transmitted infections (AOR = 3.98; 95% CI: 0.89–17.22) and were not taking antiretroviral therapy (AOR = 6.61; 95% CI: 2.25–19.37) had higher odds of being in a large cluster (size > 4). Conclusion: Comprehensive HIV prevention packages should include behavioral and biological components, including early diagnosis and treatment of both HIV and bacterial sexually transmitted infections to optimally reduce the risk of HIV transmission and acquisition. Correspondence to Yuruo Li, Department of Epidemiology, University of Maryland School of Public Health, 6100 Westchester Park Drive, Apt 520, College Park, MD 20740, USA. Tel: +1 404 539 6249; e-mail: yuruo.li12@gmail.com Received 6 June, 2019 Revised 24 September, 2019 Accepted 25 September, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Lesosky, Maia; Raboud, Janet M.; Glass, Tracy; Brummel, Sean S.; Ciarnello, Andrea L.; Currier, Judith S.; Essajee, Shaffiq; Havlir, Diane V.; Koss, Catherine A.; Ogwu, Anthony; Shapiro, Roger L.; Abrams, Elaine J.; Myer, Landon

Background: Intensified viral load (VL) monitoring for pregnant and breastfeeding women has been proposed to help address concerns around antiretroviral therapy (ART) adherence, viraemia and transmission risk, but there have been no systematic evaluations of existing policies. Methods: We used an individual Monte Carlo simulation to describe longitudinal ART adherence and VL from conception until two years postpartum. We applied national and international guidelines for VL monitoring to the simulated data. We compared guidelines on the percentage of women receiving VL monitoring and the percentage of women monitored at the time of elevated VL. Results: Coverage of VL monitoring in pregnancy and breastfeeding varied markedly, with between 14–100% of women monitored antenatally and 38–98% monitored during breastfeeding. Specific recommendations for testing at either a fixed gestation or a short, fixed period after ART initiation achieved >95% testing in pregnancy but this was much lower (14–83%) among guidelines with no special stipulations. By the end of breastfeeding, only a small proportion of simulated episodes of elevated VL > 1000 copies/mL were successfully detected by monitoring (range, 20–50%). Discussion: While further research is needed to understand optimal VL frequency and timing in this population, these results suggest that current policies yield suboptimal detection of elevated VL in pregnant and breastfeeding women. Correspondence to Maia Lesosky, Division of Epidemiology & Biostatistics, School of Public Health & Family Medicine, University of Cape Town Faculty of Health Sciences, Anzio Road, Observatory 7925, South Africa. Tel: +27(0)216504532; e-mail: lesosky@gmail.com Received 17 June, 2019 Revised 30 August, 2019 Accepted 13 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

del Amo, Julia; Jarrín, Inma; the IeDEA and COHERE in EuroCoord Cohort Collaboration

Background: Women account for over half of persons living with HIV/AIDS globally. We examined geographic variation in all-cause mortality after antiretroviral therapy (ART) for women living with HIV (WLWH) worldwide. Methods: We pooled data from WLWH at least 18 years initiating ART 2000–2014 within COHERE (Europe) and IeDEA regions (East Africa, West Africa, South Africa, North America, Latin America/Caribbean). Mortality rates were calculated at 0–3, 3–6, 6–12, 12–24 and 24–48 months after ART, and mortality rate ratios were compared with European rates with piecewise exponential parametric survival models based on Poisson regression. Findings: Nineteen thousand, one hundred and seventy-five WLWH (16% Europe, 47% East Africa, 13% West Africa, 19% South Africa, 1% South America, 3% North America and 2% Central America/Caribbean) were included. The highest death rates occurred 0–3 months after ART [1.51 (95% CI 1.25–1.82) per 100 person-years in Europe, 12.45 (11.30–13.73), 14.03 (13.12–15.02) and 9.44 (8.80–10.11) in East, West and South Africa, and 1.53 (0.97–2.43), 7.83 (5.44–11.27) and 17.02 (14.62–19.81) in North, South America and Central America/Caribbean, respectively] and declined thereafter. Mortality in Europe was the lowest, with regional differences greatest in the first 3 months and smaller at longer ART durations [adjusted rate ratios 24–48 months after ART: 3.63 (95% CI 3.04–4.33), 5.61 (4.84–6.51) and 3.47 (2.97–4.06) for East, West and South Africa; 2.86 (2.26–3.62), 2.42 (1.65–3.55) and 2.50 (1.92–3.26) for North, South America and Central America/Caribbean, respectively]. Conclusion: Global variations in short-term and long-term mortality among WLWH initiating ART may inform context-specific interventions. Correspondence to Julia del Amo, National Plan on HIV/AIDS/STIs, Ministry of Health, Consumer Affairs and Social Well being, Madrid, Spain. E-mail: jamo@mscbs.es Received 17 June, 2019 Revised 3 September, 2019 Accepted 13 September, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Gandhi, Monica; Wang, Guohong; King, Roger; Rodrigues, Warren C.; Vincent, Michael; Glidden, David V.; Cressey, Tim R.; Bacchetti, Peter; Spinellii, Matthew A.; Okochi, Hideaki; Siriprakaisil, Oraphan; Klinbuayaem, Virat; Mugo, Nelly R.; Ngure, Kenneth; Drain, Paul K.; Baeten, Jared M.

Objective: HIV prevention and treatment studies demonstrate that pharmacologic adherence metrics are more accurate than self-report. Currently-available metrics use liquid-chromatography/tandem-mass-spectrometry (LC-MS/MS), which is expensive and laboratory-based. We developed a specific and sensitive antibody against tenofovir, the backbone of treatment and prevention, but conversion to a lateral flow assay (LFA) –analogous to a urine pregnancy test- is required for point-of-care testing. We describe the development of the first LFA to measure antiretroviral adherence in real-time. Methods: Previous work in a directly-observed therapy study of providing tenofovir-disoproxil fumarate (TDF) to HIV-noninfected volunteers at various simulated adherence patterns defined the appropriate cut-off for the LFA (1500ng tenofovir/ml urine). We developed the LFA using a sample pad for urine; a conjugate pad coated with TFV-specific antibodies conjugated to colloidal gold nanoparticles; a nitrocellulose membrane striped with tenofovir-antigen (test line) and a control line; with an absorbent pad to draw urine across the reaction membrane. Results: We tested 300 urine samples collected from the directly-observed therapy study by this LFA and the gold-standard method of LC-MS/MS. The LFA demonstrated 97% specificity (95% CI: 93% to 99%) and 99% sensitivity (94% to 100%) compared to LC-MS/MS. The LFA accurately classified 98% of patients who took a dose within 24 hours as adherent. Conclusion: We describe the development and validation of the first point-of-care assay to measure short-term adherence to HIV prevention and treatment in routine settings. The assay is low-cost, easy-to-perform and measures the breakdown product (tenofovir) of both TDF and tenofovir alafenamide (TAF). This assay has the potential to improve HIV and PrEP outcomes worldwide by triggering differentiated service delivery with further study merited. Correspondence to Monica Gandhi,MD, MPH, Professor of Medicine, Division of HIV, Infectious Diseases, and Global Medicine, 995 Potrero Avenue, 4th floor, Room 423D, San Francisco, CA 94110. Tel: +415 476 4082 ext 138; fax: +415 476 9653; e-mail: monica.gandhi@ucsf.edu Received 19 July, 2019 Revised 28 August, 2019 Accepted 29 August, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Chaisson, Lelia H.; Saraceni, Valeria; Cohn, Silvia; Seabrook, Dena; Cavalcante, Solange; Chaisson, Richard E.; Golub, Jonathan; Durovni, Betina

Objectives: In 2018, Brazilian guidelines changed to recommend tuberculosis (TB) preventive therapy for all people with HIV and a CD4≤350 cells/μL, but only for those with a positive tuberculin skin test (TST) if CD4> 350 cells/μL. We determined the potential effectiveness of CD4-based guidelines for TB testing and preventive therapy. Design: Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT). Methods: We analyzed data from 4,114 newly-registered patients with HIV in 29 clinics followed until TB diagnosis, death, or administrative censoring. We compared incidence rates of TB and TB/death between CD4, TST, IPT, and antiretroviral therapy (ART) categories. Results: Initial CD4 count was ≤350 in 2,138 (52%) and > 350 in 1,976 (48%) patients. TST was performed for 2,922 (71%), of whom 657 (16%) were TST-positive (278 [13%] CD4≤350 vs. 379 [19%] CD4> 350). A total of 619 (15%) received IPT and 2,806 (68%) received ART. For patients with CD4≤350 who did not receive IPT, the incidence rate of TB was 1.79/100 person-years (pys) and TB/death was 3.89/100pys. For patients with CD4> 350 who did not receive IPT, the incidence rates of TB and TB/death were 0.57/100pys and 1.49/100pys for TST-negatives, and 1.05/100pys and 1.64/100pys for TST-unknowns. Conclusions: TB incidence was high among all patients who did not receive IPT, including those with CD4> 350 and negative or unknown TST results. TB preventive therapy should be provided to all PLWH in medium burden settings, regardless of CD4 count and TST status. Correspondence to Jonathan Golub, PhD, Johns Hopkins University Center for Tuberculosis Research, 1550 Orleans Street, Cancer Research Building-2, Baltimore, MD 21287. Tel: +43-287-2969; e-mail: jgolub@jhmi.edu Received 13 August, 2019 Revised 3 September, 2019 Accepted 13 September, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Abbar, Baptiste; Baron, Marine; Katlama, Christine; Marcelin, Anne-Geneviève; Veyri, Marianne; Autran, Brigitte; Guihot, Amélie; Spano, Jean-Philippe

Immune checkpoint inhibitors (ICPi) have shown major therapeutic successes when used in various cancers. In the HIV field a double benefit of such ICPi should result from their dual ability to restore in-vitro HIV-specific CD8+ T-cell functions and to enhance HIV production from reservoir cells, thus fulfilling the goals of the ‘shock and kill’ concept proposed as an HIV cure therapeutic strategy. We conducted a systematic review to identify studies reporting the tolerance profile of ICPi and their effects on HIV plasma loads (pVL), CD4+ count, HIV reservoirs (cell-associated HIV-DNA) and/or HIV-specific CD8+ T in PLWH. Thirty-four articles were included for a total 176 participants. 12.1% participants experienced severe adverse events and 49.4% nonsevere adverse events. pVL remained stable in 91.9% participant, showed increases in 5.8% participant, and decreases in 2.3%. CD4+ count remained stable in 60.7% participants, showed increases in 24.6%, and decreases in 14.7%. Regarding ICPi effects on HIV-DNA and HIV-specific immunity, we identified three distinct profiles: profile I, transient pVL increases followed by a boost in HIV-specific CD8+ T cells concomitant to a decrease in HIV-DNA, reported in one participant. Profile II: increase in HIV-specific CD8+ T cells without changes in pVL or HIV-DNA, reported in three participants. III: no effect, reported in five participants. In conclusion, the clinical, virological and immunological safety profiles of ICPi reported in about 200 PLWH appear to be favorable but their still modest results in terms of HIV cure strategy. Correspondence to Jean-Philippe Spano, MD, PhD, Hopital Universitaire, Pitie Salpetriere, F-75013 Paris, France. Tel: +33 1 42 16 04 72; fax: +33 1 42 16 04 69; e-mail: jean-philippe.spano@aphp.fr Received 13 June, 2019 Revised 6 September, 2019 Accepted 15 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Barry, Peter A.; Deere, J.D.; Yue, Y.; Chang, W.W.-L.; Schmidt, K.A.; Wussow, F.; Chiuppesi, F.; Diamond, D.J.; Sparger, E.E.; Walter, M.R.; Hartigan-O’Connor, D.J.

No abstract available…

Mazzitelli, Maria; Milinkovic, Ana; Pereira, Branca; Palmer, James; Tong, Timothy; Asboe, David; Boffito, Marta

As a consequence of ageing, the number of prescribed medications for people living with HIV (PLWH) is increasing. Concomitant use of different drugs and their potential interactions may increase anticholinergic exposure and escalate the risk for side effects. We conducted an analysis in our cohort of PLWH over 50 years of age to evaluate the overall anticholinergic risk, as it is useful to identify, prevent, and manage increased side effect risks. Correspondence to Dr Maria Mazzitelli, MD, Magna Graecia University, Catanzaro (Italy), Chelsea and Westminster Hospital, London (UK). E-mail: m.mazzitelli88@gmail.com Received 26 July, 2019 Revised 22 August, 2019 Accepted 2 September, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Meza, Giovanna; Expósito, Almudena; Royo, José Luis; Ruiz-García, Celia; Sánchez-Arcas, Beatriz; Marquez, Francisco J.; Gómez-Vidal, María Amparo; Omar, Mohamed; Sinangil, Faruk; Higgins, Keith; Forthal, Donald; Real, Luis Miguel; Caruz, Antonio

Objectives: CR2 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CR2 genetic variants are associated with susceptibility to systemic lupus erythematosus as well as to HIV-1 infection. Additionally, CR2 function can be subverted by HIV-1 for an efficient entry into target cells; in a process known as antibody-dependent enhancement of viral infection. We sought to determine the association between CR2 gene variants with HIV-1 acquisition after vaccination with recombinant gp120 protein (Vax004 clinical trial). Design and Methods: This is a retrospective cross-sectional study, comprising male subjects of European ancestry including infected (n = 273) and uninfected (n = 402) vaccinees and placebo, who were genotyped for 3 SNPs in the CR2 gene region. Results: An interaction was observed between the baseline sexual behaviour and the SNP rs3813946 for higher risk of infection in vacinees (interaction term p = 0.02). This SNP was associated with increased susceptibility to HIV-1 infection after vaccination in subjects with low behavioral risk OR [95%CI]: 5.5 [1.4–21.7], p = 0.006 but not vaccinees with high behavioral risk or subjects given placebo (p = 0.7). Moreover, CR2 genotype was strongly associated with the rate of HIV-1 acquisition after vaccination in low risk subjects (Hazard odds ratio [95%CI]: 3.3 [1.6–7.0], p = 0.001). Conclusions: This study suggests that CR2 may play a role in HIV-1 acquisition after vaccination with rgp120 proteins. Correspondence to Antonio Caruz, PhD. Immunogenetics Unit, Universidad de Jaén, Campus Las Lagunillas SN, 23071, Jaén, Spain. Tel: +34 953212706; fax: +34 953211875; e-mail: caruz@ujaen.es Received 2 August, 2019 Revised 29 August, 2019 Accepted 16 September, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Ogbuoji, Osondu; Geldsetzer, Pascal; Wong, Cebele; Khan, Shaukat; Mafara, Emma; Lejeune, Charlotte; Walsh, Fiona; Okello, Velephi; Bärnighausen, Till

Objectives: Immediate ART (or early access to ART for all, EAAA) is becoming a national policy in many countries in sub-Saharan Africa. It is plausible that the switch from delayed to immediate ART could either increase or decrease patient satisfaction with treatment. A decrease in patient satisfaction would likely have detrimental consequences for long-term retention and adherence, in addition to the value lost because of the worsening patient experience. We conducted a pragmatic stepped-wedge cluster-randomized controlled trial (SW-cRCT) to determine the causal impact of immediate treatment for HIV on patient satisfaction. Design: This seven-step SW-cRCT took place in 14 public-sector healthcare facilities in Eswatini's Hhohho region, from September 2014 to August 2017. Methods: During each step of the trial, we selected a random set of data collection days for each study facility. During these days, a random sample of HIV patients were selected for outcome assessment. In total, 2,629 patients provided data on their overall patient satisfaction and satisfaction with the following four domains of the patient experience using a 5-point Likert scale: wait time, consultation time, involvement in treatment decisions, and respectful treatment. Higher values on the Likert scale indicated lower patient satisfaction. We analyzed the data using a multilevel ordered logistic regression model with individuals at the first level and health facilities at the second (cluster) level. Results: The proportional odds ratios comparing EAAA to control were 0.91 (95% CI: 0.66, 1.25) for overall patient satisfaction. For the specific domains of the patient experience, the impact of EAAA on satisfaction was 1.04 (95% CI: 0.61, 1.78) for wait time, 0.90 (95% CI: 0.62, 1.31) for involvement in treatment decisions, 0.86 (95% CI: 0.61, 1.20) for consultation time, and 1.35 (95% CI: 0.93, 1.96) for respectful treatment. These results were robust across a wide range of sensitivity analyses. Over time – and independent of EAAA – we observed a worsening trend for both overall patient satisfaction and for satisfaction within all four domains of the patient experience that we measured. Conclusions: Our main findings support the policy change from delayed to immediate ART in sub-Saharan Africa. We find no impact of immediate (versus delayed) ART in public-sector health facilities in Eswatini on either overall patient satisfaction or on satisfaction with four specific domains of the patient experience. At the same time, we observed a strong secular trend of decreasing patient satisfaction in both the intervention and the control arm of the trial, which may be due to the generally increasing numbers of patients on ART. Further implementation research should identify approaches to ensure high patient satisfaction, as ART programs grow and mature. This trial was registered at ClinicalTrials.gov (NCT02909218). Correspondence to Osondu Ogbuoji, Boston, UNITED STATES. E-mail: oogbuoji@mail.haravrd.edu Received 14 February, 2019 Revised 9 August, 2019 Accepted 19 August, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Moran, Caitlin A.; Southmayd, Geoffrey; Devireddy, Chandan M.; Quyyumi, Arshed A.; Ofotokun, Ighovwerha; Liberman, Henry A.; Jaber, Wissam; Sheth, Anandi N.

Objectives: Persons living with HIV (PLWH) are at greater risk for acute coronary syndrome (ACS). Practice patterns of ACS management by HIV serostatus are unknown. We examined the presentation and management of ACS in PLWH. Design: Retrospective case control study. Methods: We included 86 PLWH and 263 sex- and race-matched HIV-negative controls hospitalized with ACS between 2004–2013. We performed multivariable conditional logistic regression to determine the associations between HIV serostatus and ACS type and management. Results: Both groups were predominantly of black race and male sex. PLWH were significantly younger (53 vs. 60 years) and more likely to smoke (48% vs. 31%). Among PLWH, 30% had CD4…

Fogel, Jessica M.; Sivay, Mariya V.; Cummings, Vanessa; Wilson, Ethan A.; Hart, Stephen; Gamble, Theresa; Laeyendecker, Oliver; Fernandez, Reinaldo E.; Del Rio, Carlos; Batey, D. Scott; Mayer, Kenneth H.; Farley, Jason E.; McKinstry, Laura; Hughes, James P.; Remien, Robert H.; Beyrer, Chris; Eshleman, Susan H.

Objective: To analyze HIV drug resistance among men who have sex with men (MSM) recruited for participation in the HPTN 078 study, which evaluated methods for achieving and maintaining viral suppression in HIV-infected MSM. Methods: Individuals were recruited at four study sites in the United States (Atlanta, Georgia; Baltimore, Maryland; Birmingham, Alabama; and Boston, Massachusetts; 2016–2017). HIV genotyping was performed using samples collected at study screening or enrollment. HIV drug resistance was evaluated using the Stanford v8.7 algorithm. A multi-assay algorithm was used to identify individuals with recent HIV infection. Clustering of HIV sequences was evaluated using phylogenetic methods. Results: High-level HIV drug resistance was detected in 44 (31%) of 142 individuals (Atlanta: 21%, Baltimore: 29%, Birmingham: 53%, Boston: 26%); 12% had multi-class resistance, 16% had resistance to tenofovir or emtricitabine, and 8% had resistance to integrase strand transfer inhibitors (INSTIs); 3% had intermediate-level resistance to second-generation INSTIs. In a multivariate model, self-report of ever having been on antiretroviral therapy (ART) was associated with resistance (p = 0.005). One of six recently-infected individuals had drug resistance. Phylogenetic analysis identified five clusters of study sequences; two clusters had shared resistance mutations. Conclusions: High prevalence of drug resistance was observed among MSM. Some had multi-class resistance, resistance to drugs used for pre-exposure prophylaxis (PrEP), and INSTI resistance. These findings highlight the need for improved HIV care in this high-risk population, identification of alternative regimens for PrEP, and inclusion of integrase resistance testing when selecting ART regimens for MSM in the US. Correspondence to Susan H. Eshleman, MD/PhD, Dept. of Pathology, The Johns Hopkins Medical Institutions, Ross Building, Room 646, 720 Rutland Avenue, Baltimore, MD, 21205, USA. Tel: +1 (410) 614 4734; fax: +1 (410) 502 9244; e-mail: seshlem@jhmi.edu Received 19 March, 2019 Revised 4 September, 2019 Accepted 15 September, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.