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Objective: Despite improved access to antiretroviral therapy (ART) for people living with HIV (PLHIV), HIV continues to contribute considerably to morbidity and mortality. Increasingly, advanced HIV disease (AHD) is found among PLHIV who are ART-experienced.Design: Using a multi-state model we examined associations between engagement with care and AHD on ART in South Africa.Methods: Using data from IeDEA Southern Africa, we included PLHIV from South Africa, initiating ART from 2004–2017 aged >5 years with a CD4 cell count at ART start and ≥1 subsequent measure. We defined a gap as no visit for ≥18 months. Five states were defined: “AHD on ART” (CD4…

Objective: The human endogenous protein Galectin-9 (Gal-9) reactivates latently HIV-infected cells in vitro and ex vivo, which may allow for immune-mediated clearance of these cells. However, Gal-9 also activates several immune cells, which could negatively affect HIV persistence by promoting chronic activation/exhaustion. This potential “double-edged sword” effect of Gal-9 raises the question of the overall impact of Gal-9 on HIV persistence in vivo.Design: We used the BLT (bone marrow, liver, thymus) humanized mouse model to evaluate the impact of Gal-9 on HIV persistence in vivo during antiretroviral therapy (ART).Methods: Two independent cohorts of ART-suppressed HIV-infected BLT mice were treated with either recombinant Gal-9 or PBS control. Plasma viral loads and levels of tissue-associated HIV DNA and RNA were measured by qPCR. Immunohistochemistry and HIV RNAscope were used to quantify CD4+ T, myeloid, and HIV RNA+ cells in tissues. T cell activation and exhaustion were measured by flow cytometry, and plasma markers of inflammation were measured by multiplex cytokine arrays.Results: Gal-9 did not induce plasma markers of inflammation or T cell markers of activation/exhaustion in vivo. However, the treatment significantly increased levels of tissue-associated HIV DNA and RNA compared to controls (P = 0.0007 and P = 0.011, respectively, for cohort I and P = 0.002 and P = 0.005, respectively, for cohort II). RNAscope validated the Gal-9 mediated induction of HIV RNA in tissue-associated myeloid cells, but not T cells.Conclusions: Our study highlights the overall adverse effects of Gal-9 on HIV persistence and the potential need to block Gal-9 interactions during ART-suppressed HIV infection.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective: To describe our experience evaluating and initiating individuals on long-acting (LAI) cabotegravir/rilpivirine (CAB/RPV) and evaluate factors associated with starting LAI CAB/RPV and reasons for not starting.Design: We conducted a retrospective single center study at the UC San Diego Owen ClinicMethods: We included all individuals who expressed interest in treatment with LAI CAB/RPV between April 2021 and June 2022 who had a definitive decision made on starting LAI CAB/RPV.Results: In total 383 individuals were included with 201 (52.5%) initiating LAI CAB/RPV. Those that initiated LAI CAB/PRV were younger (p = 0.02) and were more likely to be on a two-drug regimen or 1st generation integrase inhibitor regimen and less likely to be on a protease inhibitor or multi-class regimen. The most common reasons for not starting LAI CAB/RPV were inconsistent clinic attendance or difficulty being contacted and patient choice not to start. Of those that had a proviral DNA resistance test as work up for LAI CAB/RPV (n = 135) 18.5% had a resistance mutation identified that may have impacted the activity of LAI CAB/RPV.Conclusion: Despite novel challenges over half of our cohort initiated LAI CAB/RPV. Evaluating for potential NNRTI resistance is an important part of the work up for LAI CAB/RPV and proviral DNA resistance testing can be an additional tool to identify potential resistance.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Sexual uses of alcohol and drugs are pervasive among men who have sex with men (MSM) and associated with increased risk of HIV infection. However, there are limited studies related to sexual uses of alcohol and drugs among MSM in China. This study aims to describe the pattern of alcohol use, drug use, and multi-drug use during sex among Chinese MSM and to examine the association between condomless anal intercourse, group sex, commercial sex and HIV infection. Methods We conducted an online cross-sectional survey in China. Characteristics on social-demographic, sexual behaviors, and sexual uses of alcohol and drugs were collected. The associations with high-risk sexual behaviors and HIV infection were analyzed with multivariable logistic regression. Results A total of 699 MSM were included in this study. About 39.5% (230/582) of men reported sexual alcohol use in the past three months and 50.8% (355/699) reported sexual drug use. Of those reporting sexual drug use, around 10.7% (38/355) reported having multi-drug use. Factors associated with both sexual uses of alcohol and drugs included: reporting more male sexual partners (alcohol: adjusted odds ratio [aOR] = 1.77; drug: aOR = 2.12), reporting condomless anal intercourse in the past three months (alcohol: aOR = 2.08; drug: aOR = 2.08), having ever engaged in group sex (alcohol: aOR = 2.04; drug: aOR = 5.22; multi-drug: aOR = 3.52) and commercial sex (alcohol: aOR = 4.43; drug: aOR = 4.22 multi-drug: aOR = 5.07). Sexual drug use was also correlated with reported HIV-positive status (drug: aOR = 2.53, 95% CI:1.31–4.90). Conclusion Sexual uses of alcohol and drugs are prevalent among Chinese MSM. Interventions to reduce the sexual use of alcohol and other drugs may be warranted among MSM in China. …

Abstract Background Increased frequency of circulating double negative T (DNT, CD4−CD8−CD3+) cells with protective immune function has been observed in human immunodeficiency virus (HIV) infection and tuberculosis (TB). Here the role of circulating TCRαβ+ DNT cells was further investigated in HIV/TB co-infection. Methods A cross-sectional study was conducted to investigate the frequency and functional profiles of peripheral TCRαβ+ DNT cells including apoptosis, chemokine and cytokine expression among healthy individuals and patients with TB, HIV infection and HIV/TB co-infection by cell surface staining and intracellular cytokine staining combined with flow cytometry. Results Significantly increased frequency of TCRαβ+ DNT cells was observed in HIV/TB co-infection than that in TB (p < 0.001), HIV infection (p = 0.039) and healthy controls (p < 0.001). Compared with TB, HIV/TB co-infection had higher frequency of Fas expression (p = 0.007) and lower frequency of Annexin V expression on TCRαβ+ DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas+TCRαβ+ DNT cells had no significant difference. TCRαβ+ DNT cells expressed less CCR5 in HIV/TB co-infection than that in TB (p = 0.014), and more CXCR4 in HIV/TB co-infection than that in HIV infection (p = 0.043). Compared with healthy controls, TB and HIV/TB co-infection had higher frequency of TCRαβ+ DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCRαβ+ DNT cells secreted more granzyme A (p = 0.002; p = 0.002) and perforin (p < 0.001; p = 0.017) than CD4+ T cells but similar to CD8+ T cells. Conclusions Reduced apoptosis may take part in the mechanism of increased frequency of peripheral TCRαβ+ DNT cells in HIV/TB co-infection. TCRαβ+ DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection. …

Abstract Background Trans women face tremendous social inequities as well as disproportionate rates of HIV and substance use, yet disaggregated substance use data specific to trans women remain limited. Methods We conducted a secondary analysis of baseline data from the Trans*National Study (2016–2017) surveying trans women in the San Francisco Bay Area (n = 629). Multivariable logistic regression was used to analyze socio-demographic and environmental correlates of substance use, and bivariate associations between substance use and HIV-associated outcomes are presented alongside prevalence data. Results Over half (52.9%) reported using substances in the prior year, most frequently marijuana, methamphetamine, and crack/cocaine. Those with unmet gender-affirming health care needs, lack of insurance, or a history of experiencing racial violence, transphobic violence, adult housing instability, or extreme poverty had higher odds of substance use. Sex work and condomless anal sex were also independently associated with substance use. Conclusions Among this sample of trans women, substance use and substance use concurrent with sex were highly prevalent, and associated with a number of socioeconomic and health care needs. These findings corroborate the need for holistic and intersectional efforts to reduce substance use and HIV risk. …

Abstract Background Tuberculosis has remained a leading cause of death among people living with HIV (PLHIV) globally. Isoniazid preventive therapy (IPT) is the recommended strategy by the World Health Organization to prevent TB disease and related deaths among PLHIV. However, delivery and uptake of IPT has remained suboptimal particularly in countries where HIV and TB are endemic such as Tanzania. This study sought to assess contextual factors that shape delivery and uptake of IPT in Dar es Salaam region, Tanzania. Methodology We employed a qualitative case study design comprising of in-depth interviews with people living with HIV (n = 17), as well as key informant interviews with clinicians (n = 7) and health administrators (n = 7). We used thematic data analysis approach and reporting of the results was guided by the Consolidated Framework for Implementation Research (CFIR). Results Characteristics of IPT such as aligning the therapy to individual patient schedules and its relatively low cost facilitated its delivery and uptake. On the contrary, perceived adverse side effects negatively affected the delivery and uptake of IPT. Characteristics of individuals delivering the therapy including their knowledge, good attitudes, and commitment to meeting set targets facilitated the delivery and uptake of IPT. The process of IPT delivery comprised collective planning and collaboration among various facilities which facilitated its delivery and uptake. Organisational characteristics including communication among units and supportive leadership facilitated the delivery and uptake of IPT. External system factors including HIV stigma, negative cultural and religious values, limited funding as well as shortage of skilled healthcare workers presented as barriers to the delivery and uptake of IPT. Conclusion The factors influencing the delivery and uptake of IPT among people living with HIV are multifaceted and exist at different levels of the health system. Therefore, it is imperative that IPT program implementers and policy makers adopt multilevel approaches that address the identified barriers and leverage the facilitators in delivery and uptake of IPT at both community and health system levels. …

Abstract Background Sexual uses of alcohol and drugs are pervasive among men who have sex with men (MSM) and associated with increased risk of HIV infection. However, there are limited studies related to sexual uses of alcohol and drugs among MSM in China. This study aims to describe the pattern of alcohol use, drug use, and multi-drug use during sex among Chinese MSM and to examine the association between condomless anal intercourse, group sex, commercial sex and HIV infection. Methods We conducted an online cross-sectional survey in China. Characteristics on social-demographic, sexual behaviors, and sexual uses of alcohol and drugs were collected. The associations with high-risk sexual behaviors and HIV infection were analyzed with multivariable logistic regression. Results A total of 699 MSM were included in this study. About 39.5% (230/582) of men reported sexual alcohol use in the past three months and 50.8% (355/699) reported sexual drug use. Of those reporting sexual drug use, around 10.7% (38/355) reported having multi-drug use. Factors associated with both sexual uses of alcohol and drugs included: reporting more male sexual partners (alcohol: adjusted odds ratio [aOR] = 1.77; drug: aOR = 2.12), reporting condomless anal intercourse in the past three months (alcohol: aOR = 2.08; drug: aOR = 2.08), having ever engaged in group sex (alcohol: aOR = 2.04; drug: aOR = 5.22; multi-drug: aOR = 3.52) and commercial sex (alcohol: aOR = 4.43; drug: aOR = 4.22 multi-drug: aOR = 5.07). Sexual drug use was also correlated with reported HIV-positive status (drug: aOR = 2.53, 95% CI:1.31–4.90). Conclusion Sexual uses of alcohol and drugs are prevalent among Chinese MSM. Interventions to reduce the sexual use of alcohol and other drugs may be warranted among MSM in China. …

Antiretroviral therapy (ART) reduces human immunodeficiency virus type 1 (HIV-1) infection, but selection of treatment-refractory variants remains a major challenge. HIV-1 encodes 16 canonical proteins, a small number of which are the singular targets of nearly all antiretrovirals developed to date. Cellular factors are increasingly being explored, which may present more therapeutic targets, more effectively target certain aspects of the viral replication cycle, and/or limit viral escape. Unlike most other positive-sense RNA viruses that encode at least one helicase, retroviruses are limited to the host repertoire.

We estimated the effectiveness of COVID-19 vaccines against laboratory-confirmed SARS-CoV-2 infection among people living with HIV (PLWH) and compared estimates with a matched HIV-negative cohort.

Abstract Background Increased frequency of circulating double negative T (DNT, CD4−CD8−CD3+) cells with protective immune function has been observed in human immunodeficiency virus (HIV) infection and tuberculosis (TB). Here the role of circulating TCRαβ+ DNT cells was further investigated in HIV/TB co-infection. Methods A cross-sectional study was conducted to investigate the frequency and functional profiles of peripheral TCRαβ+ DNT cells including apoptosis, chemokine and cytokine expression among healthy individuals and patients with TB, HIV infection and HIV/TB co-infection by cell surface staining and intracellular cytokine staining combined with flow cytometry. Results Significantly increased frequency of TCRαβ+ DNT cells was observed in HIV/TB co-infection than that in TB (p < 0.001), HIV infection (p = 0.039) and healthy controls (p < 0.001). Compared with TB, HIV/TB co-infection had higher frequency of Fas expression (p = 0.007) and lower frequency of Annexin V expression on TCRαβ+ DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas+TCRαβ+ DNT cells had no significant difference. TCRαβ+ DNT cells expressed less CCR5 in HIV/TB co-infection than that in TB (p = 0.014), and more CXCR4 in HIV/TB co-infection than that in HIV infection (p = 0.043). Compared with healthy controls, TB and HIV/TB co-infection had higher frequency of TCRαβ+ DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCRαβ+ DNT cells secreted more granzyme A (p = 0.002; p = 0.002) and perforin (p < 0.001; p = 0.017) than CD4+ T cells but similar to CD8+ T cells. Conclusions Reduced apoptosis may take part in the mechanism of increased frequency of peripheral TCRαβ+ DNT cells in HIV/TB co-infection. TCRαβ+ DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection. …

Physical frailty is one of the major concerns among aging people living with HIV. A comprehensive meta-analysis exploring the association between physical frailty and negative health outcomes among people living with HIV is lacking.

ABSTRACT: Background: Vaporized nicotine (VN) use is increasing among people with HIV (PWH). We examined demographics, patterns of use, depression, and panic symptoms associated with VN and combustible cigarette (CC) use among PWH.Methods: We analyzed VN use among PWH in care at 7 US sites. PWH completed a set of patient-reported outcomes, including substance use and mental health. We categorized VN use as never vs. ever with frequency of use (days/month) and CC use as never, former, or current. We used relative risk regression to associate VN and CC use, depression, and panic. Linear regression estimated each relationship with VN frequency. Models were adjusted for demographics.Results: Among 7,431 PWH, 812 (11%) reported ever-using VN, and 264 (4%) reported daily use. Half (51%) of VN users concurrently used CC. VN users were more likely than those without use to be younger, white, and to report ever-using CC. PWH reporting former CC use reported ≥8.5 more days per month of VN use compared to never CC use (95%CI: 5.5-11.5 days/month) or current (95%CI: 6.6-10.5 days/month). Depression (RR: 1.20 [95%CI: 1.02-1.42]) and panic disorder (1.71 [95%CI: 1.43-2.05]) were more common among PWH ever-using VN. Depression was common among PWH using VN (27%) and CC (22%), as was panic disorder (21% for VN, 16% for CC).Conclusion: Our study elucidated demographic associations with VN use among PWH, revealed overlap of VN and CC use, and associations with depression/panic symptoms, suggesting roles of VN in self-medication and CC substitution, warranting further longitudinal/qualitative research.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Trans women face tremendous social inequities as well as disproportionate rates of HIV and substance use, yet disaggregated substance use data specific to trans women remain limited. Methods We conducted a secondary analysis of baseline data from the Trans*National Study (2016–2017) surveying trans women in the San Francisco Bay Area (n = 629). Multivariable logistic regression was used to analyze socio-demographic and environmental correlates of substance use, and bivariate associations between substance use and HIV-associated outcomes are presented alongside prevalence data. Results Over half (52.9%) reported using substances in the prior year, most frequently marijuana, methamphetamine, and crack/cocaine. Those with unmet gender-affirming health care needs, lack of insurance, or a history of experiencing racial violence, transphobic violence, adult housing instability, or extreme poverty had higher odds of substance use. Sex work and condomless anal sex were also independently associated with substance use. Conclusions Among this sample of trans women, substance use and substance use concurrent with sex were highly prevalent, and associated with a number of socioeconomic and health care needs. These findings corroborate the need for holistic and intersectional efforts to reduce substance use and HIV risk. …

Abstract Background Tuberculosis has remained a leading cause of death among people living with HIV (PLHIV) globally. Isoniazid preventive therapy (IPT) is the recommended strategy by the World Health Organization to prevent TB disease and related deaths among PLHIV. However, delivery and uptake of IPT has remained suboptimal particularly in countries where HIV and TB are endemic such as Tanzania. This study sought to assess contextual factors that shape delivery and uptake of IPT in Dar es Salaam region, Tanzania. Methodology We employed a qualitative case study design comprising of in-depth interviews with people living with HIV (n = 17), as well as key informant interviews with clinicians (n = 7) and health administrators (n = 7). We used thematic data analysis approach and reporting of the results was guided by the Consolidated Framework for Implementation Research (CFIR). Results Characteristics of IPT such as aligning the therapy to individual patient schedules and its relatively low cost facilitated its delivery and uptake. On the contrary, perceived adverse side effects negatively affected the delivery and uptake of IPT. Characteristics of individuals delivering the therapy including their knowledge, good attitudes, and commitment to meeting set targets facilitated the delivery and uptake of IPT. The process of IPT delivery comprised collective planning and collaboration among various facilities which facilitated its delivery and uptake. Organisational characteristics including communication among units and supportive leadership facilitated the delivery and uptake of IPT. External system factors including HIV stigma, negative cultural and religious values, limited funding as well as shortage of skilled healthcare workers presented as barriers to the delivery and uptake of IPT. Conclusion The factors influencing the delivery and uptake of IPT among people living with HIV are multifaceted and exist at different levels of the health system. Therefore, it is imperative that IPT program implementers and policy makers adopt multilevel approaches that address the identified barriers and leverage the facilitators in delivery and uptake of IPT at both community and health system levels. …

AbstractBackgroundDespite effective prevention approaches, ongoing HIV-1 transmission remains a public health concern indicating a need for identifying its drivers.MethodsWe combine a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV-1 transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission.ResultsWe find that only a minority of clusters and patients acquire links to new infections between 2007 and 2020. While the growth of clusters and the probability of individual patients acquiring new links in the transmission network was associated with epidemiological, behavioral and virological predictors, the strength of these associations decreased substantially when adjusting for network characteristics. Thus, these network characteristics can capture major heterogeneities beyond classical epidemiological parameters. When modeling the probability of a newly diagnosed patient being linked with future infections, we found that the best predictive performance (median AUCROC = 0.77) was achieved by models including characteristics of the network as predictors and that models excluding them performed substantially worse (median AUCROC = 0.54).ConclusionsThese results highlight the utility of molecular epidemiology-based network approaches for analysing and predicting ongoing HIV-1-transmission dynamics. This approach may serve for real-time prospective assessment of HIV-1-transmission.

EDITORIAL…

Objective: Women with HIV (WWH) have heightened heart failure (HF) risk. Plasma OPN (osteopontin) is a powerful predictor of HF outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated HF risk.Design: Prospective, cross-sectionalMethods: We analyzed relationships between plasma OPN and cardiac structure/ function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH).Results: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ=0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ=0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ=0.49, P = 0.03) and myocardial steatosis (ρ=0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on non-classical (CD14-CD16+) monocytes (whole group:ρ=0.36, P = 0.04; WWH:ρ=0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH:ρ=0.54, P = 0.01; WWOH:ρ=0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters.Conclusions: Among WWH, plasma OPN, a powerful predictor of HF outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in HF pathogenesis among WWH.Clinicaltrials.gov Registration: NCT02874703Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Objective: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).Design: Cross-sectional.Methods: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).Results: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1–Q3) CVD risk was 4.5% (2.6–6.9). Forty percentage had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH (≥5). Coronary plaque was present in 357 (49%); 167 (23%) had ≥1 vulnerable plaque features, 293 (40%) had noncalcified plaque, and 242 (35%) had a coronary artery calcium score >0. All three phenotypes were increasingly more prevalent with poorer CVH and these relationships remained after adjusting for ASCVD risk. Poor CVH was associated with higher high-sensitivity C-reactive protein, oxidized low-density cholesterol, and interleukin-6. The relationship of LS7 to plaque remained after adjusting for these biomarkers.Conclusions: Among PWH, poor CVH as measured by LS7 was associated with coronary plaque presence, vulnerable features, and calcification. LS7 was also associated with selected biomarkers; adjustment for these and ASCVD score reduced but did not eliminate LS7's association with plaque, suggesting the possibility of additional protective mechanisms against atherogenesis and plaque remodeling. Clinical use of LS7 and further exploration of its relationships with coronary artery disease may enhance efforts to reduce cardiovascular morbidity and mortality in PWH.Clinical Trials Registration: NCT02344290Graphical abstract, http://links.lww.com/QAD/C694Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: Evaluating the vascular function in HIV+ compared to HIV- with assessment of body composition, inflammation, and gut integrity markers.Design: A non-invasive test that measures the endothelial function.Methods: We included participants ≥18 years, with peripheral arterial tonometry testing (EndoPAT2000) between 2014-2022. Persons living with HIV (PLWH) had documented infection, a stable ART regimen, and a Viral Load…

Clusters of cases of pneumocystis pneumonia and Kaposi’s sarcoma in New York and California in men who had sex with men were early harbingers of the acquired immunodeficiency syndrome (AIDS) epidemic. The syndrome was also soon noted to be associated with a high incidence of aggressive B-cell lymphomas. As the AIDS definition crystallized, Kaposi’s sarcoma, aggressive B-cell lymphomas, and invasive cervical cancer were considered to be AIDS-defining cancers when they developed in patients with human immunodeficiency virus (HIV) infection. Additional cancers are now known to be associated with HIV (Table 1). The term HIV-associated cancer is used here to describe this larger group of cancers (both AIDS-defining and non–AIDS-defining cancers) that have an increased incidence among patients with HIV infection. In addition, incidental cancers also may develop in patients with HIV infection.

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.