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.

Moses Katbi, Adeoye Ayodeji Adegboye, Maryam Bello, Aliyu Gambo Gumel, Adefisayo Adedoyin, Fadimatu Yunusa, Gbenga Kayode, Oche Baba Yusuf, Atinuke Anjorin, Chizoba Geraldine Abone, Amalachukwu Ukaere, Ernest Ekong, Charles Mensah, Patrick Dakum

Folayan M, Haire B, Noseda V.

To the Editor—The article by Lelièvre [1] and his reference to that by Lelièvre and Hocqueloux [2] discuss whether preexposure prophylaxis (PrEP) should be provided to the partners of HIV-positive research participants who undergo analytical treatment interruptions (ATIs) in HIV cure research. Lelièvre and Hocqueloux argue that new analyses of data from the 2006 SMART study [3] show that ATIs do not compromise health when initiated in people with high CD4 counts and no previous HIV-related illness [1].

Dee L, Boone C, Palm D, et al.

To the Editor—We are writing to express concerns regarding facts reported in 2 recent Journal of Infectious Diseases articles [1, 2] pertaining to the ANRS-LIGHT study, conducted in 18 clinical sites in France between September 2013 and May 2015. Initially, we were delighted to see the authors implemented several inclusion criteria that we believe were likely to ensure safety of participants during the analytical treatment interruption (ATI) that occurred during the trial, for example a nadir of CD4+ T-cell count of ≥300 cells/mm3 and an initial CD4+ T-cell count of ≥600/mm3 [3]. However, other aspects are dismaying, including the detailed identifying information about the index participant and partner. We fear it is possible to identify both persons from the elaborate medical and nonmedical history provided. After contacting the study Principal Investigator, Dr Lelièvre, through a European colleague, it appears there were no consents to disclose this information. Thus, we feel strongly that it was inappropriate to include such comprehensive, potentially identifying details.

Abstract Background The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. Methods TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. Results Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012–2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007–2011) and period 2 (2012–2015). Conclusions A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.…

Labuda S, Huo Y, Kacanek D, et al.

AbstractBackgroundStudies from multiple countries have suggested impaired immunity in perinatally HIV-exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the U.S. Among HEUs, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of child hospitalization.MethodsHEU data from subjects enrolled in the Surveillance Monitoring for ART Toxicities Study (SMARTT) cohort who were born 2006-2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fit to evaluate associations of maternal HIV factors with risk of hospitalization.ResultsA total of 2,404 HEU and 3,605,864 HUU were included in the analysis. HEU children had ~2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared to HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization.ConclusionsCompared to HUU, HEU children in the US have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

Palich R, Veyri M, Valantin M, et al.

AbstractWe report 21 cases of cutaneous and/or visceral Kaposi’s sarcoma occurring in HIV-infected patients on antiretroviral therapy with suppressed HIV viremia and high CD4 T cell counts. Efficacy of conventional chemotherapies was limited due to cumulative toxicities, comedications and lack of immune improvement. Alternative treatments should be evaluated.

López-Centeno B, Badenes-Olmedo C, Mataix-Sanjuan Á, et al.

AbstractBackgroundDrug-drug interactions (DDIs) involving antiretrovirals (ARVs) tend to cause harm if unrecognized, especially in the context of multiple co-morbidity and polypharmacy.MethodsA database linkage was established between the regional drug dispensing registry of Madrid and the Liverpool HIV DDI database (January-June 2017). Polypharmacy was defined as the use of ≥5 non-HIV medications, and DDIs were classified by a traffic-light ranking for severity. HIV-uninfected controls were also included.ResultsA total of 22,945 patients living with HIV (PLWH) and 6,613,506 uninfected individuals had received medications. Antiretroviral therapy regimens were predominantly based on integrase inhibitors (51.96%). Polypharmacy was significantly higher in PLWH (32.94%) than uninfected individuals (22.16%; P

Abstract Background Women living with HIV (WLWH) have high rates of persistent high-risk human papillomavirus (hrHPV) infections and cervical cancer. We aimed to assess the distribution of hrHPV genotypes, risk factors of type-specific hrHPV persistence, and high-grade squamous intraepithelial lesions or worse (≥HSIL) in WLWH in Denmark. Methods From the prospective Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) we identified WLWH with a positive hrHPV test during the study period; 2011–2014. HIV demographics were retrieved from the Danish HIV Cohort Study and pathology results from the The Danish Pathology Data Bank. Logistic regression was used to identify risk factors associated with persistent hrHPV infection (positivity of the same hrHPV type in two samples one-two years after the first hrHPV positive date) and ≥ HSIL. Results Of 71 WLWH, 31 (43.7%) had persistent hrHPV infection. Predominant hrHPV genotypes were HPV58, 52, 51, and 35 and most frequently observed persistent genotypes were HPV52, 33 and 31. CD4 

Scott, Hyman M.; Spinelli, Matthew; Vittinghoff, Eric; Morehead-gee, Alicia; Hirozawa, Anne; James, Catherine; Hammer, Hali; Liu, Albert; Gandhi, Monica; Buchbinder, Susan

Objective: Dissemination of pre-Exposure Prophylaxis (PrEP) is a priority for reducing new HIV infections, especially among vulnerable populations. However, there are limited data available on PrEP discontinuation following initiation, an important component of the PrEP cascade. Design: Patients receiving PrEP within the San Francisco Department of Public Health Primary Care Clinics (SFPCC) are included in a PrEP registry if they received a PrEP prescription, were not receiving post-exposure prophylaxis, and not known to be HIV positive. Methods: We calculated PrEP discontinuation for patients initiating PrEP at any time from January 2012 to July 2017 and evaluated their association with demographic and risk variables using Cox regression analysis. Results: Overall, 348 patients received PrEP over the evaluation period. The majority (84%) were men, and the cohort was racially/ethnically diverse. The median duration of PrEP use was 8.3 months. In adjusted analysis, PrEP discontinuation was lower among older patients (aHR 0.89; 95% CI: 0.80–0.99; p = 0.03); but higher among Black patients (compared with White patients) (aHR 1.87; 95%CI: 1.27–2.74; p = 0.001), patients who inject drugs (aHR 4.80; 95%CI 2.66–8.67; p …

Anderson, Albert M.; Pérez-Santiago, Josué; Zheng, Ziduo; Huang, Eugene; Franklin, Donald; Iudicello, Jennifer; Moore, David J.; Ellis, Ronald J.; Heaton, Robert K.; Letendre, Scott L.

Objective: HIV-associated neurocognitive impairment continues to be prevalent and clinically relevant. We examined the relationship between neurocognition and full plasma HIV RNA suppression among study participants over a 15 year period at a large research program. Design/Methods: We analyzed the combined prospective studies of the HIV Neurobehavioral Research Program (HNRP) at the University of California at San Diego. Participants were eligible for analysis if on three drug cART with comprehensive neuropsychological testing results. Participants who reported recent non-adherence were excluded. The primary outcome was plasma HIV RNA of ≤50 copies/ml. Generalized estimating equation was used to assess for associations with full virologic suppression taking into account longitudinal visits. Results: There were 1943 participants at baseline, of whom 69.4% had plasma HIV RNA ≤50 copies/ml. Participants with full suppression were slightly older, less likely to abuse cocaine, and had significantly better executive function. Multivariate analysis with incorporation of longitudinal visits (total = 5555) confirmed current cocaine abuse to be strongly associated with lack of virologic suppression (odds ratio = 0.45, 95% confidence interval = 0.31–0.63). In contrast, increasing age, increasing years of HIV infection, and increasing executive function (odds ratio = 1.18 for T score change of 10, 95% confidence interval = 1.07–1.30) were associated with full virologic suppression. Lack of virologic suppression at baseline was associated with a significant subsequent decline in executive function. Conclusions: In a 15 year research cohort of almost 2000 HIV-infected individuals on cART, better executive function was associated with full virologic suppression, possibly as a result rather than a cause. Correspondence to Albert M. Anderson, MD, MHS, Emory University School of Medicine, Atlanta, United States. e-mail: aande2@emory.edu Received 15 March, 2019 Revised 8 July, 2019 Accepted 24 July, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Fan Jin, Xiao-hang Liu, Wen-can Chen, Zhang-ling Fan, Huan-ling Wang

Wong, Alexander; Goldstein, Deborah; Mallolas, Josep; DeJesus, Edwin; Johnson, Margaret; Molina, Jean-Michel; Pozniak, Anton; Rodgers, Anthony; Teal, Valerie; Hepler, Deborah; Kumar, Sushma; Sklar, Peter; Hanna, George J; Hwang, Carey; Badshah, Cyrus; Teppler, Hedy

No abstract available…

Chikwari, Chido Dziva; Njuguna, Irene N.; Neary, Jillian; Rainer, Crissi; Chihota, Belinda; Slyker, Jennifer A.; Katz, David A.; Wamalwa, Dalton C.; Oyiengo, Laura; Bandason, Tsitsi; McHugh, Grace; Dauya, Ethel; Mujuru, Hilda; Stewart, Kearsley A; John-Stewart, Grace C.; Ferrand, Rashida A.; Wagner, Anjuli D.

Background: Gaps persist in HIV testing for children who were not tested in prevention of mother-to-child HIV transmission programs. Oral mucosal transudate rapid HIV tests (OMT) have been shown to be highly sensitive in adults but their performance has not been established in children. Methods: ART-naïve children aged 18 months to 18 years in Kenya and Zimbabwe were tested for HIV using rapid OraQuick ADVANCE Rapid HIV-1/2 Antibody test on oral fluids (OMT) and blood-based rapid diagnostic testing (BBT). BBT followed Kenyan and Zimbabwean national algorithms. Sensitivity and specificity were calculated using the national algorithms as the reference standard. Results: A total of 1,776 children were enrolled; median age was 7.3 years (IQR: 4.7, 11.6). Among 71 children positive by BBT, 71 were positive by OMT (sensitivity: 100% [97.5%CI: 94.9-100%]). Among the 1,705 children negative by BBT, 1,703 were negative by OMT (specificity: 99.9% [95%CI: 99.6-100.0%]). Due to discrepant BBT and OMT results, 2 children who initially tested BBT negative and OMT positive were subsequently confirmed positive within 1 week by further tests. Excluding these 2 children, the sensitivity and specificity of OMT compared to BBT were each 100% (97.5%CI: 94.9-100% and 99.8-100%, respectively). Conclusions: Compared to national algorithms, OMT did not miss any HIV-positive children. These data suggest that OMTs are valid in this age range. Future research should explore the acceptability and uptake of OMT by caregivers and health workers to increase pediatric HIV testing coverage. Corresponding Author: Chido Dziva Chikwari Biomedical Research and Training Institute 10 Seagrave Road, Avondale Harare, Zimbabwe Tel: +263772773879/+2634745583 Email: Chido.DzivaChikwari@lshtm.ac.uk The authors report no conflicts of interest related to this work. * Joint first authors Funding: The study in Zimbabwe was jointly funded by the Duke Global Health Institute, the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID concordat agreement and is also part of the EDCTP2 programme supported by the European Union (MR/P011268/1). The Saliva Testing and Video Information to Expand Uptake of Pediatric HIV Testing (STEP-UP) study was funded by the National Institutes of Health (NIH; P30 AI027757 [CFAR New Investigator Award; PI: Wagner]) and the Thrasher Research Foundation (A119882). INN, DAK, JN, ADW were supported by P30 AI027757. ADW was also supported by A119882. INN was supported by Fogarty International Centre (FIC) D43TW009783. This publication was supported by the University of Washington Global Center for the Integrated Health of Women, Adolescents, and Children (Global WACh). This publication was funded in part by the University of Washington / Fred Hutch Center for AIDS Research, and NIH funded program under award number AI027757, which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

I. Rooms et al.

Akdag D, Knudsen A, Thudium R, et al.

AbstractBackgroundPrior to the introduction of combination antiretroviral therapy (cART), cytopenias were common in people with HIV (PWH), but it is unknown if well-controlled HIV infection is a risk factor for cytopenia. In this study we aimed to determine if HIV infection is an independent risk factor for anemia, neutropenia, lymphocytopenia, and thrombocytopenia.MethodsPWH with undetectable viral replication and absence of chronic hepatitis infection (n=796) were recruited from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched uninfected controls from the Copenhagen General Population Study (n=2388). Hematology was analyzed in venous blood samples. Logistic regression analyses adjusted for age, sex, ethnicity, smoking status, alcohol, and hs-CRP were performed to determine possible associations between HIV and cytopenias.ResultsPWH had a higher prevalence of anemia (6.9% vs. 3.4%, P

Tassiopoulos K, Huo Y, Patel K, et al.

AbstractBackgroundYoung adults with perinatally-acquired HIV (YPHIV) living in the United States are transitioning to adult clinical care, yet there is little information on factors that affect transition outcomes.MethodsYPHIV ≥18 years old in the PHACS (Pediatric HIV/AIDS Cohort Study) AMP Up cohort approaching or having completed transition from pediatric to adult healthcare were included. Demographic and clinical characteristics and self-reported ability to self-manage healthcare were compared by transition status, and multivariable logistic regression models examined factors associated with satisfaction with, and retention in, adult clinical care (clinic visit within the previous 6 months).ResultsMost of the 455 YPHIV, regardless of transition status, reported satisfaction with their clinic and care provider, but many reported antiretroviral medication non-adherence. Of the 124 YPHIV who had transitioned, 56% had periods of unsuppressed HIV-1 RNA in the year prior to transition. Those who had transitioned were more likely to report high ability to self-manage their healthcare (ability to manage ≥7 of 8 skills) than those not transitioned. High self-management was associated with retention after transition (odds ratio=3.40, 95% CI=1.33, 9.12). Higher perceived emotional social support was also associated with retention. Older age at transition was associated with greater satisfaction with provider and clinic.ConclusionsYPHIV have positive associations with their clinical care around the time of their transition to adult care, but unsuppressed viral load and suboptimal adherence are a concern. Strengthening skills that increase ability to self-manage care and enhance social support may increase retention in care and improve clinical health.

Trevillyan J, Moser C, Currier J, et al.

AbstractA retrospective case control analysis determined that following adjustment for hsCRP, presence of traditional cardiovascular risk factors and CD4/CD8 T cell ratio, higher lipopolysaccharide binding protein (LBP) was associated with future myocardial infarction in HIV. LBP may be a novel marker of cardiovascular risk with specific utility in HIV.

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) in HIV endemic settings is a major threat to public health. MDR-TB is a substantial and underreported problem in Sub-Saharan Africa (SSA), with recognised cases projected to increase with advancement in diagnostic technology. There is paucity of review evidence on treatment outcomes and antiretroviral (ART) uptake among MDR-TB patients with HIV in SSA. To address this gap a review of treatment outcomes in HIV patients co-infected with MDR-TB in the SSA region was undertaken. Methods Three databases (Medline, Web of Science, CINHAL), Union on Lung Heath conference proceedings and grey literature were searched for publications between January 2004 and May 2018. Records were assessed for eligibility and data extracted. Random effect meta-analysis was conducted using STATA and Cochrane’s review manager. Results A total of 271 publications were identified of which nine fulfilled the inclusion criteria. Data was collected from 3368 MDR-TB and HIV co-infected patients from four SSA countries; South Africa (6), Lesotho (1), Botswana (1) and Ethiopia (1). The most common outcome was cure (34.9% cured in the pooled analysis), this was followed by death (18.1% in pooled analysis). ART uptake was high, at 83% in the pooled analysis. Cure ranged from 28.6 to 54.7% among patients on ART and from 22.2 to 57.7%  among those not on ART medication. MDR-TB and HIV co-infected patients were less likely to be successfully treated than HIV negative MDR-TB patients (Risk Ratio = 0.87, 95% CI 0.97, 0.96). Conclusion Treatment outcomes for MDR-TB and HIV co-infected patients do not vary widely from those reported globally. However, treatment success was lower among HIV positive MDR-TB patients compared to HIV negative MDR-TB patients. Prompt antiretroviral initiation and interventions to improve treatment adherence are necessary.…

Abstract Background Female sex workers (FSWs) at substantial risk of HIV are potentially a suitable group for HIV prevention trials including vaccine trials. Few HIV vaccine preparatory studies have been conducted among FSWs in Sub-Saharan Africa (SSA); data are therefore limited on acceptability of vaccine trial procedures. We determined vaccination completion and one-year retention among FSWs in Kampala, Uganda. Methods We conducted a prospective study that simulated a vaccine efficacy trial among HIV negative FSWs (18–49 years). Hepatitis B vaccine (Engerix B) was used to mimic an HIV vaccine product. Volunteers received 1 ml intramuscular injection at 0, 1 and 6 months, and made additional visits (3 days post-vaccination and months 3, 9 and 12). They were censored at that visit if diagnosed as HIV positive or pregnant. We collected socio-demographic, behavioral and clinical data at baseline, 6 and 12 months and fitted Poisson regression models with robust standard error to find factors associated with vaccination completion and retention. Results We enrolled 290 volunteers (median age 27 years) of whom 230 reached a study end-point as follows: 7 became HIV infected, 11 became pregnant and 212 completed both the vaccination schedule and 12-month visit giving a retention of 77.9% (212/272). Vaccination completion was 82.4%. Non-retention at 1 year was more likely among those reporting symptoms of genital ulcer disease (GUD) in the past 3 months (IRR 1.90; 95% CI 1.09–3.32) and those

Abstract Background Since 2000, substantial increases in syphilis in men who have sex with men (MSM) have been reported in many cities. Condomless anal sex (CAS) is one of the factors, along with drugs for sex and sex in group. This study identified factors and clinical manifestations as well as Treponema pallidum (T.pallidum) strains that could be related to early syphilis in Barcelona. Methods This prospective study was conducted in a sexually transmitted infections unit in 2015. Epidemiological, behavioral, clinical and microbiological variables were collected in a structured form. Univariate and multivariate statistical analyses were performed focusing on HIV-positive patients. Results Overall, 274 cases were classified as having early syphilis (27.5% primary, 51.3% secondary, and 21.2% early latent syphilis). In all, 94% of participants were MSM and 36.3% were HIV-positive. The median number of sexual contacts in the last 12 months was 10; 72.5% practiced CAS, 50.6% had sex in group, and 54.7% consumed drugs. HIV-positive cases had more anonymous sex contacts (p = 0.041), CAS (p = 0.002), sex in group (p