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An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented.

BackgroundHuman immunodeficiency virus (HIV) infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity.MethodsWe studied persons with HIV (PWH) and HIV-negative (HIV-) individuals who had used cannabis recently. We assessed 2 biomarkers of BBB permeability: the cerebrospinal fluid (CSF) to serum albumin ratio (CSAR) and CSF levels of soluble urokinase plasminogen activator receptor (suPAR), a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay.ResultsParticipants were 45 PWH and 30 HIV- individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r = 0.47, P

People living with HIV infection (PWH) disclose that cannabis is an effective strategy for alleviating symptoms associated with HIV disease. However, some medical providers feel ill-informed to engage in evidence-based conversations. HIV leads to alterations in the gut microbiome, gut-brain axis signaling, and chronic inflammation. The endocannabinoid system regulates homeostasis of multiple organ systems. When deficient, dysregulation of the gut-brain axis can result in chronic inflammation and neuroinflammation. Cannabis along with the naturally occurring endocannabinoids has antioxidant and anti-inflammatory properties that can support healing and restoration as an adjunctive therapy. The purpose of this literature review is to report the physiologic mechanisms that occur in the pathology of HIV and discuss potential benefits of cannabinoids in supporting health and reducing the negative effects of comorbidities in PWH.

Persistent inflammation occurs in people with HIV (PWH) and has many downstream adverse effects including myocardial infarction, neurocognitive impairment and death. Because the proportion of people with HIV who use cannabis is high and cannabis may be anti-inflammatory, it is important to characterize the impact of cannabis use on inflammation specifically in PWH. We performed a selective, non-exhaustive review of the literature on the effects of cannabis on inflammation in PWH. Research in this area suggests that cannabinoids are anti-inflammatory in the setting of HIV. Anti-inflammatory actions are mediated in many cases through effects on the endocannabinoid system (ECS) in the gut, and through stabilization of gut-blood barrier integrity. Cannabidiol may be particularly important as an anti-inflammatory cannabinoid. Cannabis may provide a beneficial intervention to reduce morbidity related to inflammation in PWH.

The biological mechanisms underlying emotional distress in HIV infection are likely to be complex but remain understudied. We investigated whether dysbiotic signatures in the gut microbiome of persons living with HIV (PLWH) are associated with their emotional status. We retrospectively examined the gut microbiome and clinical evaluation of 129 adults (94 PLWH and 35 HIV−) enrolled at UC San Diego's HIV Neurobehavioral Research Program. A subset of participants (32 PLWH vs. 13 HIV−) underwent an emotional assessment using the NIH Toolbox Emotion Battery summarized by three composite scores (negative affect, social satisfaction, and psychological well-being). We then sequenced the 16S rDNA V3-V4 regions from stool and performed taxonomic assignment using CLC Microbial Genomics Module. The gut microbiota profiles were evaluated in relation to participants' emotional assessment. All analyses were done in R statistical software. We found that the relative abundance of aerotolerant bacteria was significantly higher in PLWH (p < 0.01) and was associated with a lifetime major depression diagnosis independently of HIV status (p = 0.05). Moreover, PLWH experienced significantly worse psychological well-being (p = 0.02), less social satisfaction (p = 0.03), and more negative affect (p = 0.02). Higher levels of aerotolerant bacteria were associated with worse psychological well-being (rho = -0.35, p = 0.02), less social satisfaction (r = − 0.42, p < 0.01), and more negative affect (rho = 0.46, p < 0.01). The association of aerotolerant bacteria with social satisfaction and negative affect was independent of HIV status (p < 0.05, for both). The over-representation of aerotolerant bacteria in the gut may reflect worse oxidative stress and barrier defects and may contribute to emotional distress during HIV infection. [ABSTRACT FROM AUTHOR]

Background: Botswana is close to reaching the UNAIDS “90-90-90” HIV testing, antiretroviral treatment (ART), and viral suppression goals. We sought to determine HIV incidence in this setting with both high HIV prevalence and high ART coverage. Methods: We used a cross-sectional approach to assessing HIV incidence. A random, population-based sample of adults age 16–64 years was enrolled in 30 rural and peri-urban communities as part of the Botswana Combination Prevention Project (BCPP), from October 2013 –November 2015. Data and samples from the baseline household survey were used to estimate cross-sectional HIV incidence, following an algorithm that combined Limiting-Antigen Avidity Assay (LAg-Avidity EIA), ART status (documented or by testing ARV drugs in plasma) and HIV-1 RNA load. The LAg-Avidity EIA cut-off normalized optical density (ODn) was set at 1.5. The HIV-1 RNA cut-off was set at 400 copies/mL. For estimation purposes, the Mean Duration of Recent Infection was 130 days and the False Recent Rate (FRR) was evaluated at values of either 0 or 0.39%. Results: Among 12,610 individuals participating in the baseline household survey, HIV status was available for 12,570 participants and 3,596 of them were HIV positive. LAg-Avidity EIA data was generated for 3,581 (99.6%) of HIV-positive participants. Of 326 participants with ODn ≤1.5, 278 individuals were receiving ART verified through documentation and were considered to represent longstanding HIV infections. Among the remaining 48 participants who reported no use of ART, 14 had an HIV-1 RNA load ≤400 copies/mL (including 3 participants with ARVs in plasma) and were excluded, as potential elite/viremic controllers or undisclosed ART. Thus, 34 LAg-Avidity-EIA-recent, ARV-naïve individuals with detectable HIV-1 RNA (>400 copies/mL) were classified as individuals with recent HIV infections. The annualized HIV incidence among 16–64 year old adults was estimated at 1.06% (95% CI 0.68–1.45%) with zero FRR, and at 0.64% (95% CI 0.24–1.04%) using a previously defined FRR of 0.39%. Within a subset of younger individuals 16–49 years old, the annualized HIV incidence was estimated at 1.29% (95% CI 0.82–1.77%) with zero FRR, and at 0.90% (95% CI 0.42–1.38%) with FRR set to 0.39%. Conclusions: Using a cross-sectional estimate of HIV incidence from 2013–2015, we found that at the time of near achievement of the UNAIDS 90-90-90 targets, ~1% of adults (age 16–64 years) in Botswana’s rural and peri-urban communities became HIV infected annually. [ABSTRACT FROM AUTHOR]

Background. Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Methods. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Results. Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48,95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income,<$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). Conclusion. Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. [ABSTRACT FROM AUTHOR]

Background: Prophylactic cotrimoxazole is recommended for infants born to HIV-infected mothers. However, cotrimoxazole may increase the risk of severe anemia or neutropenia. Methods: We compared the proportion of HIV-exposed uninfected (HIV-EU) infants experiencing incident severe anemia (and separately, severe neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole from 1 to 6 months vs. infants from two prior trials who did not receive cotrimoxazole. Infants were from rural and urban communities in southern Botswana. Results: A total of 1705 HIV-EU infants were included. Among these 645 (37.8%) were fed with iron-supplemented formula from birth. Severe anemia developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In an analysis stratified by infant feeding method, there were no significant differences in the risk of severe anemia by prophylactic cotrimoxazole exposure–risk difference, −0.69% (95% confidence interval [CI] −2.1 to 0.76%). Findings were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI 0.07 to 1.65). There were also no significant differences observed for severe neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI −1.3 to 5.2%) and aOR 0.80 (95% CI 0.33 to 1.93). Conclusions: Severe anemia and severe neutropenia were infrequent among HIV-exposed uninfected infants receiving cotrimoxazole from 1–6 months of age. Concerns regarding hematologic toxicity should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected infants. ClinicalTrials.gov Registration Numbers: NCT01086878 (http://clinicaltrials.gov/show/NCT01086878), NCT00197587 (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296 (http://clinicaltrials.gov/show/NCT00270296). [ABSTRACT FROM AUTHOR]

Background Cancer is now the leading cause of mortality for persons living with HIV (PLWH) in the United States, but it is uncertain whether PLWH access cancer screening that could lower this burden. We sought to assess cancer screening for breast, cervical, and colon cancer among PLWH compared with the HIV-uninfected population at a multicenter healthcare system over the past two decades. Methods Data were obtained from a prospective, observational HIV clinical care cohort comprised of PLWH engaged in care in the Partners Healthcare System. Patients eligible for cancer screening between the years 2002 and 2016 were included. Patients were matched in a maximum of 1:4 ratio with HIV-uninfected patients from the Massachusetts General Primary Care Practice-Based Research Network based on age, sex, race, year of study entry, and length of follow-up. The mean proportion of time in which eligible patients were guideline concordant for cervical, breast, and colon cancer screening was assessed. Non-parametric tests were used to compared screening rates between PLWH and HIV-infected and on the basis of multiple clinical and sociodemographic factors. Results During the observation period, a total of 495 PLWH were eligible for breast cancer screening, 1011 for cervical cancer screening, and 1965 for colon cancer screening. For each screening group, the majority of PLWH were on antiretroviral therapy (ART) and had relatively high CD4 cell counts (Table 1). Screening rates for PLWH compared with controls were 67.3% vs. 82.8% (P < 0.0001) for breast cancer, 49.0% vs. 73.3% (P < 0.0001) for cervical cancer, and 92.7% vs. 91.2% (P = 0.96) for colon cancer (Figure 1). Among PLWH, factors significantly associated with lower rates of screening guideline concordance were older age, lower CD4 count, HIV-1 RNA >1000 copies/mL, and HIV duration < 5 years for breast cancer, and older age, white race, English language, and lack of ART use for cervical cancer. Conclusion Among patients engaged in longitudinal care, PLWH had significantly lower rates of screening for breast and cervical cancer than HIV-uninfected. Disparity is not explained by racial or primary language differences. Further work to improve access to cancer screening for PLWH is needed. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults account for more than one-third of incident Human Immunodeficiency Virus (HIV) infections globally. Understanding sexual practices of this high-risk group is critical in designing HIV targeted prevention programming. Objectives: To describe self-reported risky sexual practices of adolescents and young adults aged 16–24 years from 30 Botswana communities. Methods: Cross-sectional, self-reported age at sexual debut; number of sexual partners; condom and alcohol use during sex; intergenerational sex; and transactional sex data were collected. Modified Poisson estimating equations were used to obtain univariate and multivariate-adjusted prevalence ratios (PR) and 95% confidence intervals (CI) comparing engagement in different sexual practices according to gender, accounting for the clustered design of the study. Results: Among the 3380 participants, 2311 reported being sexually active with more females reporting being sexually active compared to males (65% vs. 35%, respectively; p < 0.0001). In univariate analyses, female participants were more likely to report inconsistent condom use (PR 1.61; 95% CI 1.44–1.80), intergenerational sex (PR 9.00; 95% CI 5.84–13.88) and transactional sex (PR 3.46; 95% CI 2.07–5.77) than males, yet less likely to report engaging in sex before age 15 years (PR 0.59; 95% CI: 0.41–0.85), using alcohol around the time of intercourse (PR: 0.59; 95% CI 0.45–0.76) or having ≥ two partners in the last 12 months (PR 0.65; 95% CI 0.57–0.74). Conclusions: Self-reported risky sexual practices of adolescents and young adults in Botswana differed significantly between males and females. Gender-specific risky sexual practices highlight the importance of developing tailored HIV prevention programming. [ABSTRACT FROM AUTHOR]

Background: Before introduction of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), 3-drug antiretroviral therapy (ART) was associated with increased adverse birth outcomes when used for prevention of mother-to-child HIV transmission (PMTCT) in Botswana. Methods: We extracted obstetric records from all women at the 2 largest maternities in Botswana from 2009-2011 when Botswana National Guidelines recommended zidovudine (ZDV) from 28 weeks gestational age (GA) for CD4 ≥350 and ART for CD4 <350, and again in 2013-2014 after implementation of TDF/FTC/EFV for prevention of mother-to-child HIV transmission regardless of CD4 or GA. We compared the use of TDF/FTC/EFV in pregnancy with other 3-drug ART regimens, and with initiation of ZDV, among women with similar CD4 cell counts. Outcomes included small for gestational age (SGA), preterm delivery (PTD) (<37 weeks GA), and stillbirths (SB). Results: Among 9445 HIV-infected women delivering during the study period, 170 were on TDF/FTC/EFV at conception and 1468 initiated TDF/FTC/EFV during pregnancy. Adverse birth outcomes were high overall (3% SB, 21% PTD, and 18% SGA) and among women receiving TDF/FTC/EFV (3% SB, 22% PTD, and 12% SGA). There was no difference in PTD or SB among women initiating TDF/FTC/ EFV compared with ZDV or other 3-drug ART, but initiating TDF/FTC/ EFV was associated with fewer SGA infants than other 3-drug ART (adjusted odds ratio: 0.4, 95% confidence interval: 0.2 to 0.7). Conclusions: Adverse birth outcomes remain high among HIV-infected women. TDF/FTC/EFV was at least as safe as other ART and associated with fewer SGA infants when initiated during pregnancy. Larger studies are needed to evaluate birth outcomes and congenital abnormalities among women on TDF/FTC/EFV at conception. [ABSTRACT FROM AUTHOR]

The article presents a study on the effect of highly active antiretroviral therapy (HAART) on the growth of HIV-uninfected infants in Botswana. It states that HIV-infected pregnant women from four sites in Botswana and HIV-uninfected infants were the subjects of the study. The study use the World Health Organization Child Growth Standards to calculate the growth of the infants. It concludes that the lower weights on HAART-exposed uninfected infants can be corrected in the first six months of life.