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.

Abstract Introduction Late presentation to HIV/AIDS care which is attended by problems like, poor treatment outcomes, early development of opportunistic infections, increased healthcare costs, and mortality is a major problem in Ethiopia. Although evidences are available on the prevalence and associated factors of late presentation to HIV/AIDS care, discrepancies among findings are appreciated. Thus, the country has faced difficulties of having a single estimated data. Objective This study aimed to estimate the pooled prevalence of late presentation of HIV positive adults to HIV/AIDS care and its predictors in Ethiopia. Method We searched all available articles through Google Scholar, PubMed, Web of Sciences, and EMBASE databases. Additionally, we accessed articles from the Ethiopian institutional online research repositories and reference lists of included studies. We included cohort, case- control, and cross-sectional studies in our review. Besides, we utilized the weighted inverse variance random-effects model. The total percentage of variation among studies due to heterogeneity was determined by I2 statistic. Searching was limited to studies conducted in Ethiopia and published in the English language. Publication bias was checked by Egger’s regression test. Results A total of 8 studies with 7, 568 participants were included. The pooled prevalence of late presentation to HIV/AIDS care was 52.89% (95%CI: 35.37, 70.40). The odds of late presentation to HIV/AIDS care of frequent alcohol users [3.67(95% CI = 1.52–5.83)], high fear of stigma [3.90 (95% CI = 1.51–6.28)], chronic illness [3.34(95% CI = 1.52–5.16)], and the presence of symptoms at the time of HIV diagnosis [3.06 (95% CL = 1.18–4.94)] were higher compared to participants who did not experience the preceding. Conclusion The prevalence of late presentation of HIV positive adults to HIV/AIDS care was high in Ethiopia. Frequent alcohol use, high fear of stigma, chronic illness, and the presence of symptoms at the time of HIV diagnosis were associated with high odds of late presentation to HIV/AIDS care. Trial registration Registered in PROSPERO databases with the registration number of CRD42018081840.…

Abstract Background Several factors have been identified as being associated with increased adherence to antiretroviral therapy, including sero-status disclosure; however, studies examining the effect of disclosure on ART adherence in Ethiopia have had inconsistent findings. This systematic review and meta-analysis therefore aims to estimate the pooled effect of disclosure on adherence to ART among adults living with HIV in Ethiopia. Methods We performed a systematic search for articles reporting on peer-reviewed, quantitative, English-language observational studies of reporting the association between self sero-status disclosure and good ART adherence in adults living with HIV/AIDS in Ethiopia during published from 2010 to 2015. We searched four electronic databases: PubMed/Medline, the World Health Organization’s Hinari portal (which includes the SCOPUS, African Index Medicus, and African Journals Online databases) for studies from December 1, 2017 to January 30, 2018. We also searched university repositories and conference abstracts for unpublished studies. We conducted a meta-analysis for the pooled effect of adherence using a random effects model in Stata version 14 and assessed publication bias using the Egger’s test for funnel plot asymmetry. Results Our search returned in 179 studies, of which seven (3.9%), were eligible and included in the final meta-analysis. The seven included studies were conducted from 2010 to 2015. Our analysis found that disclosure had a significant effect on the adherence to ART in adult patients living with HIV. Patients who disclosed were 1.64 times more likely to have good adherence to ART compared with those who did not (OR: 1.64, 95% CI: 1.11, 2.42). The small number of studies eligible for review and differences in study definitions of adherence and disclosure were the main limitations of this study. Conclusion This review found a statistically significant positive effect of disclosure status on the adherence to ART in adult patients living with HIV in Ethiopia. This suggests that Ethiopia’s national treatment and prevention programs should redouble efforts to encourage self-disclosure among people living with HIV/AIDS. Encouraging supportive social environments for disclosure, and promoting partner notification and partner disclosure support initiatives might be particularly helpful in this regard.…

A. Giacomelli, M. Fabbiani, I. Benedetto, S. Nozza, E. Focà, B.M. Celesia, G. Marchetti, C. Mussini, A. Antinori, G. d’Ettorre, G. Madeddu, A. Bandera, A. Muscatello, S. Rusconi, on behalf of the INACTION study group

Journal of Medical Virology, Volume 0, Issue ja, -Not available-.

Laura E. Carreto-Binaghi, Fernando R. Morales-Villarreal, Guadalupe García-de la Torre, Tania Vite-Garín, Jose-Antonio Ramirez, El-Moukhtar Aliouat, Jose-Arturo Martínez-Orozco, Maria-Lucia Taylor

Abstract Background As technology progresses, several highly sensitive human immunodeficiency virus (HIV) screening kits are being researched and developed to quickly and efficiently identify serum HIV antibodies within the non-window period. In individuals who are HIV-seronegative, HIV infections that are not within a window period are rare. In such cases, all antibody detection methods will fail, and misdiagnosing these patients will have catastrophic consequences. Case presentation A 22-year-old male Chinese patient with diffuse exudative lesions in both lungs and initial symptoms of cough and dyspnoea was diagnosed with Pneumocystis jirovecii pneumonia (PJP) by aetiological examination, and the patient’s plasma CD4+ T-cell count was extremely low. In China, PJP is prevalent in HIV-infected individuals. Pneumocystis jirovecii (P. jirovecii) has a high colonisation rate in patients with HIV infections. This patient was naturally suspected of being an HIV patient; however, serum HIV antibody tests were negative using both an enzyme-linked immunosorbent assay (ELISA) and a latex agglutination assay, and HIV was not detected by western blotting. Subsequently, the plasma HIV viral load was found to be extremely high on two repeated plasma HIV RNA tests, thus confirming HIV-seronegative acquired immunodeficiency syndrome (AIDS) in this patient. With administration of effective anti-P. jirovecii treatment and highly active antiretroviral therapy (HAART) after diagnosis, the patient’s disease condition was rapidly controlled. Conclusion This is the second reported case in China of an HIV-seronegative AIDS patient. Such cases are also rare worldwide. Although HIV-seronegative HIV infections are rare, AIDS should be considered in immunodeficient patients with opportunistic infections, even if the test results are HIV-seronegative. Plasma HIV RNA testing is important for such patients.…

Myron S Cohen

In December, 2011, Science recognised the findings of the HPTN 052 study1 as the scientific breakthrough of the year.2 This study showed a 96% reduction in sexual transmission of HIV in serodifferent couples (one partner HIV positive, the other HIV negative) when the HIV-positive partner was successfully treated with antiretroviral therapy (ART).1 However, the HPTN 052 study included only a small number of men who have sex with men (MSM), for whom HIV acquisition often includes anal exposure, an efficient route of HIV transmission.

Alison J Rodger, Valentina Cambiano, Tina Bruun, Pietro Vernazza, Simon Collins, Olaf Degen, Giulio Maria Corbelli, Vicente Estrada, Anna Maria Geretti, Apostolos Beloukas, Dorthe Raben, Pep Coll, Andrea Antinori, Nneka Nwokolo, Armin Rieger, Jan M Prins, Anders Blaxhult, Rainer Weber, Arne Van Eeden, Norbert H Brockmeyer, Amanda Clarke, Jorge del Romero Guerrero, Francois Raffi, Johannes R Bogner, Gilles Wandeler, Jan Gerstoft, Felix Gutiérrez, Kees Brinkman, Maria Kitchen, Lars Ostergaard, Agathe Leon, Ma

Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.

Abstract Background Heterosexual transmission is the main driver of the HIV epidemic in Tanzania. Only one estimate of the incidence rate of intra-marital HIV seroconversion in Tanzania has been reported and was derived from data collected between 1991 and 1995. Moreover, little is known about the specific risk factors for intra-marital seroconversion in Tanzania. Improved evidence around factors that increase the risk of HIV transmission to a serodiscordant spouse is needed to develop and improve evidence-based interventions. We sought to investigate the rate of intra-marital HIV seroconversion among HIV sero-discordant couples in Tanzania as well as its associated risk factors. Methods We identified all HIV positive individuals in the TAZAMA HIV-serosurvey cohort and followed up their serodiscordant spouse from 2006 to 2016. The rate of seroconversion was analyzed by survival analysis using non-parametric regressions with exponential distribution. Results We found 105 serodiscordant couples, 14 of which had a seroconverting spouse. The overall HIV-1 incidence rate among spouses of people with HIV-1 infection was 38.0 per 1000 person/years [22.5–64.1]. Notably, the HIV-1 incidence rate among HIV-1 seronegative male spouses was 6.7[0.9–47.5] per 1000 person/years, compared to 59.3 [34.4–102.1] per 1000 person/years among female spouses. Sex of the serodiscordant spouse was the only significant variable, even after adjusting for other variables (Hazard rate = 8.86[1.16–67.70], p = 0.036). Conclusions Our study suggests that rates of HIV-1 seroconversion of sero-discordant partners are much higher within marriage than in the general population in Tanzania. The major risk factor for HIV-1 seroconversion is sex of the serodiscordant spouse, with female spouses being at very high risk of acquiring HIV infection. This suggests that future programs that target serodiscordant couples could be a novel and effective means of preventing HIV-1 transmission in Tanzania.…

Morsica, Giulia; Galli, Laura; Bossolasco, Simona; Bagaglio, Sabrina; Vercesi, Riccardo; Salpietro, Stefania; Hasson, Hamid; Messina, Emanuela; Castagna, Antonella; Uberti-Foppa, Caterina

Background: Human immunodeficiency virus (HIV)-1 infection impairs cellular immunity, causing a detrimental effect on the natural course of hepatitis B virus (HBV) infection. HBV vaccination is less effective in HIV-1-infected patients. This study aimed to gain insight into HIV-1 infection with persistence of hepatitis B surface antigen (HBsAg) defining chronic hepatitis B infection (CBI) after a primary infection, and the possible associated factors. Setting: Division of Infectious Diseases, San Raffaele Hospital, Italy. Methods: This retrospective study analyzed HIV-1-infected patients diagnosed with acute hepatitis B infection (AHB) based on clinical or laboratory records. CBI was defined as a positive HBsAg result recorded >6 months after an AHB diagnosis. Multivariate logistic regression was applied to assess factors (evaluated at AHB diagnosis) that were associated with CBI. Results: Of 63 HIV-1-infected patients with AHB, 23 (36.5%) developed CBI. On multivariate analysis, CBI risk was less likely in patients with HIV-RNA of >50 copies/mL (adjusted odds ratio [AOR]=0.03, 95% confidence interval [CI]: 0.001-0.58, p=0.021). Dually acting antiretroviral therapy (DAART), including one or more drugs active against HIV/HBV (lamivudine, emtricitabine, tenofovir), appeared to be protective in terms of the clinical outcome of CBI (AOR=0.07, 95% CI: 0.01-1.02, p=0.050). Among the 23 patients with CBI, 15 (65.2%) lost the hepatitis B e-antigen, while 11 (47.8%) had HBsAg seroclearance during follow-up. Conclusions: In HIV-1-infected subjects with AHB, the persistence of HBsAg seemed to occur frequently. Factors associated with a lower CBI risk were detectable HIV load and the use of DAART during AHB. Corresponding Author: Giulia Morsica, Division of infectious Diseases , via Stamira d’Ancona, 20 20127 Milan, Italy Email:morsica.giulia@hsr.it Tel. +390226437935 Fax. +390226437989 Conflict of interest: Castagna A. has received consultancy payments and speaking fee from Bristol-Myers, Squibb, Gilead, AbbVie, ViiV Health Care, Merck Sharp & Dohme, Janssen-Cilag. The other Authors (Giulia Morsica, Laura Galli, Simona Bossolasco, Sabrina Bagaglio, Riccardo Vercesi, Stefania Salpietro, Hamid Hasson, Emanuela Messina, Caterina Uberti-Foppa) have declared that no competing interests exist. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Johnson, Kelly A.; Hessol, Nancy A.; Kohn, Robert; Nguyen, Trang Q.; Mara, Elise S.; Hsu, Ling; Scheer, Susan; Cohen, Stephanie E.

Background: The comparative effectiveness of pre and post-exposure prophylaxis (PrEP and PEP) for men who have sex with men (MSM) is unclear. Setting: We conducted a case-control study of MSM who were initially HIV-uninfected during 9/1/2012 – 6/30/2016 at San Francisco’s only municipal sexually transmitted diseases (STD) clinic. Methods: Each case was matched with up to three controls based on age, baseline visit date, and follow-up time. The primary dependent variable was HIV seroconversion; the primary independent variable was exposure to PrEP, PEP, or neither. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Results: Of 638 MSM (161 cases, 477 controls), 137 reported ever taking PrEP, 98 reported taking PEP only, and 403 took neither. PrEP takers had more non-HIV STDs during the analysis (72.3% vs. 55.1% vs. 42.4% p

Noël, Nicolas; Gominet, Marie; Meyer, Laurence; Boufassa, Faroudy; Lambotte, Olivier

No abstract available…

Walker N, Opondo C, Meintjes G, et al.

AbstractRationaleTuberculosis (TB) is the leading cause of mortality and morbidity in people living with HIV infection. HIV-infected patients with TB disease are at risk of the paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) when they commence anti-retroviral therapy. However, the pathophysiology is incompletely understood and specific therapy is lacking.ObjectivesWe investigated the hypothesis that invariant Natural Killer T (iNKT) cells contribute to innate immune dysfunction associated with TB-IRIS.MethodsIn a cross-sectional study of 101 HIV-infected and -uninfected South African patients with active TB and controls, iNKT cells were enumerated using α-galactosylceramide-loaded CD1d tetramers and subsequently functionally characterised by flow cytometry. In a second study of 49 HIV-1-infected TB patients commencing anti-retroviral therapy, iNKT cells in TB-IRIS patients with non-IRIS controls were compared longitudinally.Measurements and main resultsCirculating iNKT cells were reduced in HIV-1 infection, most significantly the CD4+ subset, which was inversely associated with HIV-1 viral load. iNKT cells in HIV-associated TB had increased surface CD107a expression, indicating cytotoxic degranulation. Relatively increased iNKT cell frequency in HIV-infected patients with active TB was associated with development of TB-IRIS following anti-retroviral therapy initiation. iNKT cells in TB-IRIS were CD4+CD8- subset deplete and degranulated around the time of TB-IRIS onset.ConclusionsReduced iNKT cell CD4+ subsets as a result of HIV-1 infection may skew iNKT cell functionality towards cytotoxicity. Increased CD4- cytotoxic iNKT cells may contribute to immunopathology in TB-IRIS.

Abstract Purpose Due to early antenatal screening and treatment, HIV mother-to-child transmission (MTCT) rarely occurs in Germany. The study aimed to investigate the impact on prevalence of HIV infection in the antenatal population and the incidence of late-presenting HIV-infected mothers attributable to increased numbers of refugees. Methods Retrospective analysis and comparison were performed for all deliveries in HIV-infected pregnant women presenting to medical care in Munich (southern Germany) and Hamburg (northern Germany) covering two time periods, A (2010–2012) and B (2013–2015). Results In Munich, deliveries in HIV-infected pregnant women increased 1.6-fold from period A (n = 50) to B (n = 79) with late-presenting cases rising significantly from 2% (1/50) in period A to 13% (10/79) in B. In contrast, late-presenting cases in Hamburg decreased from 14% (14/100) in period A to 7% (7/107) in B, while the total number of HIV-infected women giving birth remained stable. From 2010 to 2015, one late-presenting pregnant woman transmitted HIV in Munich by presumed in utero mode of infection (case reviewed here), while no MTCT occurred in Hamburg. Conclusions HIV infections diagnosed late in pregnancy and leading to delayed ART initiation are rising in Munich compared to Hamburg. Antenatal care of HIV-infected pregnant women in Munich appears to have been more affected by the recent refugee influx than Hamburg. Our study highlights the importance of screening all pregnant women for HIV early in pregnancy and providing timely health care access for pregnant refugees and asylum seekers to effectively prevent MTCT in Germany.…

, Owens DK, Davidson KW, et al.

This 2019 Recommendation Statement from the US Preventive Services Task Force recommends offering preexposure prophylaxis (PrEP) with effective antiretroviral therapy to persons at high risk of HIV acquisition (A recommendation).

Chou R, Evans C, Hoverman A, et al.

This systematic review to support the 2019 US Preventive Services Task Force guideline on preexposure prophylaxis (PrEP) for the prevention of HIV infection summarizes published evidence on the benefits and harms of preexposure antiretroviral therapy in adults without preexisting HIV infection.

Scott H, Volberding PA.

Physicians practicing in rapidly evolving areas of medical care, and policy makers charged with supporting that care, both benefit from informed guidance regarding testing, new treatments, and innovations in disease prevention. Approaches to HIV care and prevention have both been improved by access to such guidance. Clinicians who care for patients with HIV follow newly published or presented data, the opinion of respected experts, and guidelines created by governmental or private organizations. Guideline groups have various “rules” regarding the inclusion of expert opinion, which publications are allowed, and how critically those research reports are evaluated. Clinicians expect guidelines to rapidly incorporate new data, and many immediately use guidelines to improve care for their patients.

Jin J.

This JAMA Patient Page describes the US Preventive Services Task Force’s recent recommendations on prevention of HIV infection with preexposure prophylaxis (PrEP).

Abstract Background Although Option B+ may be more costly than Options B, it may provide additional health benefits that are currently unclear in Yunnan province. We created deterministic models to estimate the cost-effectiveness of Option B+. Methods Data were used in two deterministic models simulating a cohort of 2000 HIV+ pregnant women. A decision tree model simulated the number of averted infants infections and QALY acquired for infants in the PMTCT period for Options B and B+. The minimum cost was calculated. A Markov decision model simulated the number of maternal life year gained and serodiscordant partner infections averted in the ten years after PMTCT for Option B or B+. ICER per life year gained was calculated. Deterministic sensitivity analyses were conducted. Results If fully implemented, Option B and Option B+ averted 1016.85 infections and acquired 588,01.02 QALYs.The cost of Option B was US$1,229,338.47, the cost of Option B+ was 1,176,128.63. However, when Options B and B+ were compared over ten years, Option B+ not only improved mothers’ten-year survival from 69.7 to 89.2%, saving more than 3890 life-years, but also averted 3068 HIV infections between serodiscordant partners. Option B+ yielded a favourable ICER of $32.99per QALY acquired in infants and $5149per life year gained in mothers. A 1% MTCT rate, a 90% coverage rate and a 20-year horizon could decrease the ICER per QALY acquired in children and LY gained in mothers. Conclusions Option B+ is a cost-effective treatment for comprehensive HIV prevention for infants and serodiscordant partners and life-long treatment for mothers in Yunnan province, China. Option B+ could be implemented in Yunnan province, especially as the goals of elimination mother-to-child transmission of HIV and “90–90-90” achieved, Option B+ would be more attractive.…

Abstract Background Most of studies on the relationship between drug use and HIV have focused largely on people who inject drugs. Non-injecting drug use is much more common than injecting drug use, and although it can also predispose people to HIV infection, it is not widely explored. We therefore conducted this study to explore the prevalence of HIV and identify risk factors for HIV infection among people who use non-injecting drugs (PWUD) in Cambodia. Methods This cross-sectional study was conducted in 2017. The Respondent Driven Sampling method was used to recruit the study participants who were interviewed face-to-face using a structured questionnaire. Blood samples were collected for HIV and syphilis testing. A multivariable logistic regression analysis was conducted to identify risk factors associated with HIV infection. Results In total, 1367 PWUD were included in this study, whose mean age was 28.0 (SD = 7.7) years. The majority (95.1%) of the participants used methamphetamine. The prevalence of HIV was 5.7, and 35.2% of the identified HIV-positive PWUD were not aware of their status prior to the survey. After adjustment for other covariates, HIV infection remained significantly associated with being in the age group of ≥35 (AOR = 2.34, 95% CI = 1.04–6.11), having lower level of formal education of ≤ 6 years (AOR = 2.26, 95% CI = 1.04–5.15), living on the streets (AOR = 2.82, 95% CI = 1.10–7.23), perception that their HIV risk was higher as compared to that of the general population (AOR = 3.18, 95% CI = 1.27–8.62), having used injecting drugs in lifetime (AOR = 3.8, 95% CI = 1.36–4.56), and having cuts or sores around the genital area in the past 12 months (AOR = 3.42, 95% CI = 1.09–6.33). Conclusions The prevalence of HIV among PWUD in this study was more than 10 times higher than the prevalence in the general adult population. The findings reveal a higher vulnerability to HIV infection among specific sub-populations of PWUD, such as those who are homeless, who may benefit from tailored interventions that respond to their specific needs. To enhance HIV case finding, stratification of PWUD to facilitate HIV risk profiling based on socio-economic profiles and drug injection history is recommended.…

Mallayasamy, S., Chaturvedula, A., Fossler, M. J., Sale, M., Goti, V., Bumpus, N. N., Marzinke, M. A., Hendrix, C. W., Haberer, J. E., for the Partners Demonstration Project Team

The Partners Demonstration Project was a prospective, open-label, implementation science-driven study of PrEP among heterosexual HIV serodiscordant couples in Kenya and Uganda. Adherence data was collected using medication event monitoring system (MEMS®) and time of sexual activity was collected using mobile phone short messages service (SMS). Two plasma samples were collected at a single study visit. We integrated adherence, pharmacokinetics, and SMS data using a population pharmacokinetic (POPPK) model to simulate tenofovir plasma concentrations from PrEP at the time of sexual activity. In the first stage of this analysis, we used data from the current study to update a prior POPPK model of tenofovir (TFV) developed with data from the Partners PrEP Study (a phase III clinical trial). The second stage involved simulating plasma concentrations at the time of sexual activity using empirical Bayes estimates (EBEs) derived from the final model. In addition, EBEs from a previously published parent-metabolite model of TFV (MTN-001, an open label 3-way crossover study in healthy women) was used to simulate tenofovir-diphosphate (TFV-DP) concentrations. We estimated percent PrEP "coverage" as the number of reported sexual events during which simulated concentrations were above a priori threshold concentrations associated with a high degree of protection from HIV infection – plasma TFV >40 ng/mL and PBMC TFV-DP concentration >36 fmol/million cells. Percentage coverage was 72% for TFV and 81% for TFV-DP levels. These levels are consistent with a high degree of protection against HIV acquisition in this study of a pragmatic delivery model for antiretroviral-based HIV prevention.…