HIV

Abstract Background HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART. Methods From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool. Results The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p = 0.013). Conclusions The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.…

Background: Interventions to promote medication adherence and viral suppression are needed among HIV-positive individuals. We aimed to determine the feasibility, acceptability, and preliminary impact of daily financial incentives linked to real-time adherence monitoring among treatment-experienced individuals. Methods: At an HIV clinic in Philadelphia, we conducted a pilot randomized trial among treatment-experienced HIV-positive adults with unsuppressed viral loads (>400 copies/ml). Participants randomized to the intervention group were eligible for daily lottery-based financial rewards dependent on antiretroviral therapy (ART) adherence, measured by a wireless-enabled electronic pill bottle. Participants also received a financial incentive for achieving viral suppression at 3 months. The control group received the standard of care. We measured acceptance and feasibility through follow-up survey at 3 months, viral suppression at 3 months, and adherence. Results: Among 29 participants, 28 (93%) completed 3-month follow-up and 24 (83%) completed a 3-month laboratory visit. Electronic pill bottles were highly acceptable to participants, with most strongly agreeing that they worked well, were reliable, and easy to use. Among those who received the intervention, 77% were very satisfied with their experience. Among those who completed the 3-month lab visit, viral suppression was achieved by 40% in the intervention group and 29% in the control group. ART adherence ≥80% was achieved by 36% and 25% in the intervention and control groups, respectively. Conclusions: Daily financial incentives coupled with real-time adherence monitoring is a promising strategy to support ART adherence among HIV-positive individuals who are not virally suppressed. This novel approach warrants testing in a larger trial. Corresponding Author: Cedric H Bien-Gund, M.D., University of Pennsylvania, Philadelphia, UNITED STATES Conflicts of Interest and Sources of Funding: The authors declare no conflicts of interest. This research received funding support from the National Institutes of Health (P30AG034546). * denotes equal contribution as co-first authors Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

ABSTRACT: Background: Low-density lipoprotein cholesterol (LDL-C) is estimated from total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) using predefined equations which assume fixed or varying relationships between these parameters and may under- or overestimate LDL-C. Data on the performance of these equations in persons with HIV (PWH) is limited. We sought to investigate the utility of the three most widely-used methods (Friedewald, Hopkins and the recently proposed NIH equation) to predict LDL-C in PWH. Methods: We identified 7397 direct LDL-C (5219 HIV, 2127 uninfected controls, 51 seroconvertors) measurements in the Women's Interagency HIV Study (WIHS), and used the 3 equations (Friedewald, Hopkins and NIH) to calculate LDL-C. We compared the performance of the three equations utilizing root mean square error (RMSE) and coefficient of determination (R2). Results: Overall, the Friedewald equation had the best performance characteristics, outperforming Hopkins and NIH methods with lower Root Mean RMSE and higher R2 at lower triglyceride levels. However, this association did not hold true at higher triglyceride levels (quartiles 3 and 4), while the Hopkins equation had better performance characteristics in quartile 3, none of the three equations were optimal in quartile 4. After adjusting for fasting status and TG levels, HIV+ had larger mean difference compared with dLDL-C using all three methods. Conclusions: All three methods have lower accuracy in HIV+ vs HIV- women, even after adjusting for triglyceride levels and fasting status. Further research should focus on identifying methods to estimate LDL-C in HIV. Corresponding author: Sadeer Al-Kindi, MD, Assistant Professor of Medicine, Harrington Heart and Vascular Institute, University Hospitals/Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, Email: sadeer.al-kindi@uhhospitals.org, Phone: 216-844-1000 Conflicts of interest: There are no potential conflicts (financial, professional, or personal) to disclose by any of the authors (Mariam N. Rana, Chang H. Kim, Claire E. Sullivan, Chris Longenecker, Sadeer Al-Kindi). * CTL and SGA contributed equally. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

An amendment to this paper has been published and can be accessed via the original article.…

Although APOBEC3 degradation is the canonical function of HIV-1 Vif, this viral protein also induces potent cell cycle arrest through a newly defined mechanism. Here, we review recent advances in this area and propose that the scope of this activity may go beyond subversion of the host cell cycle.

Objective: To compare the incidence of dyslipidemia in people with HIV (PLWH) receiving integrase inhibitors (INSTI) versus boosted protease inhibitors (PI/b) and non-nucleoside reverse transcriptase inhibitors (NNRTI) within RESPOND consortium of prospective cohorts. Methods: Participants were eligible if they were ≥18 years, without dyslipidemia and initiated or switched to a three-drug ART-regimen consisting of either INSTI, NNRTI or PI/b for the first time, between 01/01/2012 and 31/12/2018. Dyslipidemia was defined as random total cholesterol >240 mg/dL, high-density lipoprotein 200 mg/dL, or initiation of lipid-lowering therapy. Poisson regression was used to determine the adjusted incidence rate ratios (aIRR). Follow-up was censored after three years or upon ART-regimen discontinuation or last lipid measurement or 31/12/2019, whichever occurred first. Results: Overall, 4577 PLWH were eligible (INSTI = 66.9%, PI/b = 12.5%, and NNRT = 20.6%), 1938 (42.3%) of whom were ART-naive. During 1.7 (interquartile range, 0.6–3.0) median years of follow-up, 1460 participants developed dyslipidemia (incidence rate: 191.6 per 1000 person-years, 95% confidence interval [CI] 182.0–201.7). Participants taking INSTI had a lower incidence of dyslipidemia compared to those on PI/b (aIRR 0.71; CI 0.59–0.85), but higher rate compared to those on NNRTI (1.35; CI 1.15–1.58). Compared to dolutegravir, the incidence of dyslipidemia was higher with elvitegravir/cobicistat (1.20; CI 1.00–1.43) and raltegravir (1.24; CI 1.02–1.51), but lower with rilpivirine (0.77; CI 0.63–0.94). Conclusion: In this large consortium of heterogeneous cohorts, dyslipidemia was less common with INSTI than with PI/b. Compared to dolutegravir, dyslipidemia was more common with elvitegravir/cobicistat and raltegravir, but less common with rilpivirine. Correspondence to Dathan M. Byonanebye, Biostatistics and Databases Program, Kirby Institute, Level 6, Wallace Wurth Building, UNSW Sydney NSW 2052; e-mail: dbyonanebye@kirby.unsw.edu.au Received 23 November, 2020 Accepted 23 December, 2020 Copyright © 2021 Wolters Kluwer Health, Inc.

Objective: The World Health Organization (WHO) has recommended that antiretroviral therapy be provided to all HIV patients to reduce future HIV transmission rates. However, few studies have examined this public health strategy at the population level in a real-world setting. Methods: In this longitudinal genetic-network study in Guangxi, China, the baseline and follow-up data were collected from HIV patients in 2014 and newly diagnosed HIV patients from 2015 to 2018, respectively. The prevention efficacy (PE) was used to estimate the effect of treatment-as-prevention in reducing HIV secondary transmission. Results: Among 804 newly diagnosed HIV patients during 2015–2018, 399 (49.6%) of them genetically linked to HIV patients at baseline during 2014–2017. The overall proportion of genetic linkage between newly diagnosed HIV patients during 2015–2018 with untreated and treated HIV patients at baseline during 2014–2017 was 6.2% and 2.9%, respectively. The PE in HIV transmission for treated HIV patients was 53.6% (95% CI: 42.1%-65.1%). Subgroup analyses indicated an 80.3% (95% CI: 74.8%-85.8%) reduction in HIV transmission among HIV patients who were treated for 4 years or more and had viral loads…

Tropical Medicine & International Health, Accepted Article.

The VRC01-class of broadly neutralizing antibodies targets the CD4-binding site on the HIV-envelope trimer and requires extensive somatic hypermutation to neutralize effectively. Chen et al. delineate a sequential immunization regimen with tailored immunogens that succeeds in eliciting a VRC01-class antibody with >50% breadth in an Ig-humanized-mouse model expressing diverse unmutated VRC01-class antibody precursors.

HIV-positive donor organs are increasingly being given to people with HIV on transplant waiting lists. Now, the UK is considering them for HIV-negative patients too. Jacqui Thornton reports.

Background: The coronavirus pandemic has necessitated a range of population-based measures in order to stem the spread of infection. These measures may be associated with disruptions to other health services including for gay, bisexual, and other men who have sex with men (MSM) at risk for or living with HIV. Here, we assess the relationship between stringency of COVID-19 control measures and interruptions to HIV prevention and treatment services for MSM. Setting: Data for this study were collected between 16-Apr-2020 and 24-May-2020 as part of a COVID-19 Disparities Survey implemented by the gay social networking app, Hornet. Pandemic control measures were quantified using the Oxford Government Response Tracker Stringency Index: each country received a score (0-100) based on the number and strictness of nine indicators related to restrictions, closures, and travel bans. Methods: We used a multilevel mixed-effects generalized linear model with Poisson distribution to assess the association between stringency of pandemic control measures and access to HIV services. Results: A total of 10,654 MSM across 20 countries were included. 38% (3992/10396) reported perceived interruptions to in-person testing, 55% (5178/9335) interruptions to HIV self-testing, 56% (5171/9173) interruptions to PrEP, and 10% (990/9542) interruptions to condom access. For every ten-point increase in stringency, there was a 3% reduction in the prevalence of perceived access to in-person testing (aPR: 0·97, 95%CI: [0·96, 0·98]), a 6% reduction in access to self-testing (aPR: 0·94, 95%CI: [0·93, 0·95]), and a 5% reduction in access to PrEP (aPR: 0·95, 95% CI: [0·95, 0·97]). Among those living with HIV, 20% (218/1105) were unable to access their provider; 65% (820/1254) reported being unable to refill their treatment prescription remotely. Conclusion: More stringent responses were associated with decreased perceived access to services. To minimize increases in HIV-related morbidity and mortality, innovative strategies are needed to minimize service interruptions to the community of gay men and other MSM during this and future waves of COVID-19. Corresponding Author: Amrita Rao, ScM, Email: arao24@jhu.edu, Tel. 617 780 8853, Address: 615 N. Wolfe St. E6534 Baltimore MD 21205 The authors report no conflicts of interest related to this work. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Background: Few studies have evaluated physical activity patterns or their association with vascular inflammation among youth living with perinatally-acquired HIV (YPHIV). Methods: We assessed YPHIV and youth perinatally HIV-exposed but uninfected (YPHEU) in the PHACS Adolescent Master Protocol with at least one Block physical activity questionnaire (PAQ) completed between ages 7-19 years. Physical activity metrics were: 1) daily total energy expenditure (TEE); 2) physical activity duration (PAD) defined as the minutes of daily moderate and vigorous activity. In a subgroup, we measured serum biomarkers of coagulation (fibrinogen, P-selectin) and endothelial dysfunction (sICAM, sVCAM, E-selectin) obtained within 3 months of a single PAQ. Repeated measures linear regression models were used to compare the trajectories of log-transformed TEE and PAD by HIV status, adjusting for confounders. Spearman correlations were calculated to assess the relationship of TEE and PAD with vascular biomarkers. Results: 596 youth (387 YPHIV, 209 YPHEU) completed 1552 PAQs (median PAQs completed=3). Median age at enrollment (Q1, Q3) was 11 (9, 13) years. TEE and PAD increased with age in both YPHIV and YPHEU. However, even after adjusting for confounders, YPHIV had significantly less increase per year than YPHEU for TEE (5.7% [95% Confidence Interval (CI): -9.9%, -1.4%, p=0.010] less) and PAD (5.2% [95%CI: -9.2%, -1.1%, p=0.016] less). Among 302 youth with biomarker measures (187 YPHIV, 114 YPHEU), we observed little correlation with TEE or PAD. Conclusions: Both groups had increases in physical activity levels as they aged, but YPHIV had smaller increases throughout adolescence compared to YPHEU, which may impact long-term health. Corresponding author: Sahera Dirajlal-Fargo, MS, DO, 11100 Euclid Avenue, Cleveland, OH 44106, Email: Sahera.dirajlal-fargo@uhhospitals.org, Tel: 216-844-7650, Fax: 216-844-8362 The authors report no conflicts of interest related to this work. Funding: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse; the National Institute of Allergy and Infectious Diseases; the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke; the National Institute on Deafness and Other Communication Disorders; the National Institute of Dental and Craniofacial Research; the National Cancer Institute; the National Institute on Alcohol Abuse and Alcoholism; the Office of AIDS Research; and the National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background To effectively reduce vertical HIV transmission requires a reduction of HIV prevalence and incidence among pregnant women and a full understanding of its epidemiology. The study aimed to determine the prevalence of HIV among women attending antenatal care and further determine spousal support during antenatal care attendance in rural areas in Eastern Cape province, South Africa. Methods A Cross-sectional study of women attending antenatal care in four Primary Care facilities was conducted using an interviewer-administered questionnaire which collected information on socio-demographic characteristics and medical history. Binomial logistic regression analyses were used to determine factors associated with HIV and to estimate the prevalence ratio (PR). The 95% confidence interval (95%CI) is used for precision of estimates; p≤0.05 for statistical significance. Results A total of 343 participants were included in the final analysis. The antenatal HIV prevalence was 38.2% (95%CI: 33.2–43.9). For 75% of the women, the HIV diagnosis was made 141 days before the date of the interview (median=77 days, interquartile range=42–141 days). Participants between the age of 30 to 39 years were 50% more likely to be HIV positive compared to those who were between the age of 20 to 29, these differences were statistically significant (PR=1.5; p-value=0.001). Furthermore, self-employed women were 30% less likely to be HIV positive when compared to unemployed participants, this was also statistically significant (PR=0.7; p-value

Abstract Background Little evidence exists to comprehensively estimate adolescent viral suppression after initiation on antiretroviral therapy in sub-Saharan Africa. This study examines adolescent progression along the HIV care cascade to viral suppression for adolescents initiated on antiretroviral therapy in South Africa. Methods All adolescents ever initiated on antiretroviral therapy (n=1080) by 2015 in a health district of the Eastern Cape, South Africa, were interviewed in 2014–2015. Clinical records were extracted from 52 healthcare facilities through January 2018 (including records in multiple facilities). Mortality and loss to follow-up rates were corrected for transfers. Predictors of progression through the HIV care cascade were tested using sequential multivariable logistic regressions. Predicted probabilities for the effects of significant predictors were estimated by sex and mode of infection. Results Corrected mortality and loss to follow-up rates were 3.3 and 16.9%, respectively. Among adolescents with clinical records, 92.3% had ≥1 viral load, but only 51.1% of viral loads were from the past 12 months. Adolescents on ART for ≥2 years (AOR 3.42 [95%CI 2.14–5.47], p

Abstract Background Chest X-ray (CXR) interpretation remains a central component of the current World Health Organization recommendations as an adjuvant test in diagnosis of smear-negative tuberculosis (TB). With its low specificity, high maintenance and operational costs, utility of CXR in diagnosis of smear-negative TB in high HIV/TB burden settings in the Xpert MTB/RIF era remains unpredictable. We evaluated accuracy and additive value of CXR to Xpert MTB/RIF in the diagnosis of TB among HIV-positive smear-negative presumptive TB patients. Methods HIV co-infected presumptive TB patients were recruited from the Infectious Diseases Institute outpatient clinic and in-patient medical wards of Mulago Hospital, Uganda. CXR films were reviewed by two independent radiologists using a standardized evaluation form. CXR interpretation with regard to TB was either positive (consistent with TB) or negative (normal or unlikely TB). Sensitivity, specificity and predictive values of CXR and CXR combined with Xpert MTB/RIF for diagnosis of smear-negative TB in HIV-positive patients were calculated using sputum and/or blood mycobacterial culture as reference standard. Results Three hundred sixty-six HIV co-infected smear-negative participants (female, 63.4%; hospitalized, 68.3%) had technically interpretable CXR. Median (IQR) age was 32 (28–39) years and CD4 count 112 (23–308) cells/mm3. Overall, 22% (81/366) were positive for Mycobacterium tuberculosis (Mtb) on culture; 187/366 (51.1%) had CXR interpreted as consistent with TB, of which 55 (29.4%) had culture-confirmed TB. Sensitivity and specificity of CXR interpretation in diagnosis of culture-positive TB were 67.9% (95%CI 56.6–77.8) and 53.7% (95%CI 47.7–59.6) respectively, while Xpert MTB/RIF sensitivity and specificity were 65.4% (95%CI 54.0–75.7) and 95.8% (95%CI 92.8–97.8) respectively. Addition of CXR to Xpert MTB/RIF had overall sensitivity and specificity of 87.7% (95%CI 78.5–93.9) and 51.6% (95%CI 45.6–57.5) respectively; 86.2% (95%CI 75.3–93.5) and 48.1% (95%CI 40.7–55.6) among inpatients and 93.8% (95%CI 69.8–99.8) and 58.0% (95%CI 47.7–67.8) among outpatients respectively. Conclusion In this high prevalence TB/HIV setting, CXR interpretation added sensitivity to Xpert MTB/RIF test at the expense of specificity in the diagnosis of culture-positive TB in HIV-positive individuals presenting with TB symptoms and negative smear. CXR interpretation may not add diagnostic value in settings where Xpert MTB/RIF is available as a TB diagnostic tool.…

According to UNAIDS, 23.3 million (62%) people with HIV underwent antiretroviral therapy (ART) in 2018, an increase of 1.6 million from 2017 (UNAIDS, 2019). Currently, the primary and most effective strategy for HIV/AIDS prevention and treatment is combined antiretroviral therapy, and, in particular, the first-line antiretroviral drugs are the most widely used regimens (Kanters et al., 2016). Although ART has led to substantial gains in the reduction of mortality and morbidity of HIV/AIDS, the abundant genetic diversity and rapid variation, making it impossible to completely eradicate the virus in participants (Deeks et al., 2013).

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) in HIV infected individuals is a serious threat to global efforts to combat tuberculosis. Inconsistent findings on the association between HIV infection and MDR-TB were present in many studies. We aimed to review existing data on the relationship between HIV infection and MDR-TB systematically to assess the contribution of HIV on MDR-TB worldwide. We also investigated the patterns of MDR-TB by age, country-wise income, study designs, and global regions. Methods We utilized PubMed, Google Scholar, and ScienceDirect databases to select eligible studies for meta-analysis that were published between January 12,010, and July 30, 2020. The random-effects model was used to obtain the pooled odds ratio of the crude association between HIV and MDR-TB with a 95% confidence interval. We investigated the potential publication-bias by checking funnel plot asymmetry and using the Egger’s test. Moreover, we assessed the heterogeneity using the I2 statistic. Sensitivity analysis was performed based on sample size and adjustment factors. The protocol was registered with PROSPERO-CRD42019132752. Results We identified 1603 studies through a database search, and after subsequent eliminations we selected 54 studies including 430,534 TB patients. The pooled odds of MDR-TB was 1.42 times higher in HIV-positive patients than HIV-negative patients (OR=1.42,CI=1.17–1.71, I2=75.8%). Subgroup analysis revealed that the estimated pooled odds for South-East Asian countries was 1.86, which is the highest in WHO regions (OR=1.86,CI=1.30–2.67, I2=0.00%), followed by Europe and Africa. The effect estimate was found to be higher for primary MDR-TB (OR=2.76,CI=1.70–4.46, I2=0.00%). There was also a trend towards increased odds of MDR-TB for HIV patients older than 40 years (OR=1.56,CI=1.17–2.06). The association was found to be significant in high-burden TB countries (OR=1.75, CI=1.39–2.19) and in high-income countries (OR=1.55, CI=1.06–2.27). Conclusion Such findings indicate that HIV infection raises the risk of MDR-TB, and after contrasting it with the results of the earlier pooled study, it appeared to be an upward risk trend. Moreover, we found that the risk is the highest in the South-East Asian region. A balanced allocation of resources is needed to halt both primary and secondary MDR-TB, particularly in HIV infected people with 40 years of age and older.…

Abstract Background In Morocco, of the estimated 29,000 people living with HIV in 2011, only 20% were aware of their HIV status. More than half of diagnoses were at the AIDS stage. We assumed that people who were unaware of their infection had contacts with the healthcare system for HIV indicators that might prompt the healthcare provider to offer a test. The aim was to assess missed opportunities for HIV testing in patients newly diagnosed with HIV who accessed care in Morocco. Methods A cross-sectional study was conducted in 2012–2013 in six Moroccan HIV centers. Participants were aged ≥18, and had sought care within 6 months after their HIV diagnosis. A standardized questionnaire administered during a face-to-face interview collected the patient’s characteristics at HIV diagnosis, HIV testing and medical history. Contacts with care and the occurrence of clinical conditions were assessed during the 3 years prior to HIV diagnosis. Over this period, we assessed whether healthcare providers had offered HIV testing to patients with HIV-related clinical or behavioral conditions. Results We enrolled 650 newly HIV-diagnosed patients (median age: 35, women: 55%, heterosexuals: 81%, diagnosed with AIDS or CD4 

Background. Tuberculosis (TB) is a common infection in people living with HIV. However, the risk factors for HIV/TB co-infection in second-line HIV therapy are poorly understood. We aimed to determine the incidence and risk factors for TB co-infection in SECOND-LINE, an international randomised clinical trial of second-line HIV therapy. Methods. We did a cohort analysis of TB cases in SECOND-LINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB following randomisation. Baseline factors associated with TB were analysed using Cox regression stratified by site. Results. TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI 2.1-5.1). Increased TB risk was associated with a low CD4+ cell count (≤200 cells/μL), high viral load (>200 copies/mL), low platelet count (…

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.