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Background: Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiological studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, Minnesota study., Methods: Between 2016 and 2017, 13 339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared with that of Olmsted County. In addition, demographic and HIV-related associations with MGUS were assessed., Results: Of the 515 samples randomly selected, the median age was 50 years (range = 35-80 years); 60% were female; and 38.6% were HIV positive, of whom 82.4% were on antiretroviral therapy. We found that 68 participants had evidence of MGUS, for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (odds ratio = 1.05, 95% confidence interval = 0.62 to 1.77), but among HIV-positive individuals, MGUS was less frequent for patients on antiretroviral therapy (adjusted odds ratio = 0.31, 95% confidence interval = 0.11 to 0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2%-3.4%), whereas the incidence of light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%)., Conclusion: Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Globally, women have higher herpes simplex virus type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM)., Methods: Within a randomized trial of the effect of 3 contraceptive methods-DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant-on human immunodeficiency virus (HIV) acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015 to 2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method., Results: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI], .65-.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI, .71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI, .89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55; 95% CI, 2.78-4.48)., Conclusions: In a randomized trial, we found no association between HSV-2 acquisition and use of 3 contraceptive methods., Trial Registration: ClinicalTrials.gov number NCT02550067., Competing Interests: Potential conflicts of interest. E. A. B. reports support for the present manuscript from the WHO Department of RH. D. D. reports support for the present manuscript from National Institute of Mental Health paid to the institution and grants or contracts outside of the conduct of the study from the National Institute of Allergy and Infectious Diseases paid to the institution. J. B. reports grants or contracts outside of the conduct of the study from National Institutes of Health paid to the institution; personal consulting fees from Gilead, Janssen, and Merck; employee/stock/options from Gilead; donation of study medication from Gilead and IPM; and employee outside of the submitted work for Gilead Sciences. R. S. reports direct travel reimbursements and travel scholarships for Conference on Retroviruses and Opportunistic Infections, AIDS, Infectious Diseases Society for Obstetrics and Gynecology, and International Society for Pharmacoepidemiology conferences. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Mobile women are at risk of HIV infection in sub-Saharan Africa, although we lack evidence for HIV risk among women in mobile partnerships, especially in the context of household food insecurity, a growing concern in the region., Setting: Women aged 15-59 years with a cohabitating male partner who participated in population-based HIV impact assessment surveys in Eswatini, Lesotho, Namibia, Tanzania, Uganda, and Zambia., Methods: We evaluated the association between women's and their partner's mobility (being away from home for more than 1 month or staying elsewhere) and transactional sex (selling sex or receiving money or goods in exchange for sex). We examined associations for effect measure modification by food insecurity level in the household in the past month. We used survey-weighted logistic regression, pooled and by country, adjusting for individual, partner, and household-level variables., Results: Among women with a cohabitating male partner, 8.0% reported transactional sex, ranging from 2.7% in Lesotho to 13.4% in Uganda. Women's mobility [aOR 1.35 (95% CI: 1.08 to 1.68)], but not their partner's mobility [aOR 0.91 (0.74-1.12)], was associated with transactional sex. Food insecurity was associated with transactional sex independent of mobility [aOR 1.29 (1.10-1.52)]. Among those who were food insecure, mobility was not associated with increased odds of transactional sex., Conclusion: Food insecurity and women's mobility each increased the odds of transactional sex. Because transactional sex is associated with HIV risk, prevention programs can address the needs of mobile and food-insecure women, including those in cohabitating relationships., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: South Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition., Methods: During December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16-35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12-18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection., Results: 5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05-5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV., Conclusions: HIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population., Clinical Trial Registration: ClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites., Competing Interests: The authors have declared that no competing interests exist.

With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA <1000 copies/mL among all seropositive adults) and unsuppressed viremia (HIV RNA ≥1000 copies/mL among all, regardless of HIV status) and assessed for temporal changes by conducting a trend analysis of the log ratio of proportions, using a Z statistic distribution. HIV prevalence remained stable from 2011 to 2016 [32% versus 30%, p = 0.10]. HIV incidence significantly declined 48% [2.48% versus 1.30%, p = 0.01]. Incidence remained higher among women than men [2011: 3.16% versus 1.83%; 2016: 1.76% versus 0.86%], with a smaller but significant relative reduction among women [44%; p = 0.04] than men [53%; p = 0.09]. The proportion of seropositive adults with viral load suppression significantly increased from 35% to 71% [p < .001]. The proportion of the total adult population with unsuppressed viremia decreased from 21% to 9% [p < .001]. National HIV incidence in Eswatini decreased by nearly half and viral load suppression doubled over a five-year period. Unsuppressed viremia in the total population decreased 58%. These population-based findings demonstrate the national impact of expanded HIV services in a hyperendemic country., Competing Interests: As an inventor of LAg-Avidity EIA, BSP receives royalties from the sale of test kits sold by the manufacturer per US government policy. The other authors have no conflicts of interest to disclose.

Background: High response rates in surveys are critical to ensuring that findings are unbiased and representative of the target population. Questionnaire length affects response rates, with long interviews associated with partially complete surveys, higher item nonresponse ("don't know" and "refuse" responses), and willingness to participate in future surveys. Our aim is to determine the impact of questionnaire length on blood test participation in population-based HIV surveys., Methods: Data are from population-based HIV impact assessments conducted in Zambia, Eswatini, and Lesotho in 2016-2017. The population-based HIV impact assessments consist of an interview followed by a blood draw. Consent for blood draw was obtained before the interview in Eswatini and after the interview in Zambia and Lesotho. Interview length was measured by the survey tablet as the time to complete the survey (interview duration) and the number of questions answered by the participant (questionnaire length). We assessed the effects of questionnaire length and interview duration on blood test participation using logistic regression., Results: Across all 3 surveys, the median interview duration was 16 minutes and the median number of questions was 77. In adjusted analyses, there was a negative impact of interview duration on blood draw consent for individuals with unknown status in Lesotho and a positive relationship between questionnaire length and blood draw consent in Zambia for those with HIV-negative and unknown status., Conclusion: Although interview length is an important consideration to reduce respondent burden, a longer questionnaire does not necessarily result in lower consent rates for blood testing., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months., Methods: We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART., Results: We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART., Conclusions: Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: HIV-1 risk scoring tools could help target provision of prevention modalities such as pre-exposure prophylaxis. Recent research suggests that risk scores for women aged 18-45 may not predict risk well among young women aged 18-24. We evaluated the predictive performance of age-specific risk scores compared with the existing non-age-specific VOICE risk score, developed for women aged 18-45., Methods: We conducted a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes Trial to develop and internally validate HIV-1 risk scores for women aged 18-24 and 25-35 in South Africa. Candidate predictors included baseline demographic, clinical, behavioral, and contextual characteristics readily available in clinical settings. The VOICE risk score was applied to women aged 18-35. We evaluated predictive performance of each risk score by area under the receiver operating characteristic curve (AUC)., Results: Predictive performance of all risk scores was moderate, with AUC (95% confidence interval) of 0.64 (0.60 to 0.67) among women aged 18-24, 0.68 (0.62 to 0.73) among those aged 25-35, and 0.61 (0.58 to 0.65) for the VOICE risk score applied to women aged 18-35; The AUC was similar in internal validation. Among women aged 18-24, HIV-1 incidence was high even at low risk scores, at 3.9 per 100 person-years (95% confidence interval: 3.2 to 4.7)., Conclusions: All risk scores were moderately predictive of HIV-1 acquisition, and age-specific risk scores performed only marginally better than the VOICE non-age-specific risk score. Approaches for targeted pre-exposure prophylaxis provision to women in South Africa may require more extensive data than are currently available to improve prediction.

In 2016, an estimated 1.5 million females aged 15-24 years were living with human immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the prevalence of HIV infection among adolescent girls and young women (3.4%) is more than double that for males in the same age range (1.6%) (1). Progress was assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020 targets for adolescent girls and young women in sub-Saharan Africa (90% of those with HIV infection aware of their status, 90% of HIV-infected persons aware of their status on antiretroviral treatment [ART], and 90% of those on treatment virally suppressed [HIV viral load <1,000 HIV RNA copies/mL]) (2) using data from recent Population-based HIV Impact Assessment (PHIA) surveys in seven countries. The national prevalence of HIV infection in adolescent girls and young women aged 15-24 years, the percentage who were aware of their status, and among those persons who were aware, the percentage who had achieved viral suppression were calculated. The target for viral suppression among all persons with HIV infection is 73% (the product of 90% x 90% x 90%). Among all seven countries, the prevalence of HIV infection among adolescent girls and young women was 3.6%; among those in this group, 46.3% reported being aware of their HIV-positive status, and 45.0% were virally suppressed. Sustained efforts by national HIV and public health programs to diagnose HIV infection in adolescent girls and young women as early as possible to ensure rapid initiation of ART should help achieve epidemic control among adolescent girls and young women., Competing Interests: Bharat Parekh reports receipt of royalties from CDC from the sale of LAg-Avidity Enzyme Immunoassay during conduct of the study. No other conflicts of interest were reported.

Background: Swaziland has the highest national HIV prevalence worldwide. The Swaziland HIV Incidence Measurement Survey (SHIMS) provides the first national HIV incidence estimate based on prospectively observed HIV seroconversions., Methods: A two-stage survey sampling design was used to select a nationally representative sample of men and women aged 18-49 years from 14 891 households in 575 enumeration areas in Swaziland, who underwent household-based counselling and rapid HIV testing during 2011. All individuals aged 18-49 years who resided or had slept in the household the night before and were willing to undergo home-based HIV testing, answer demographic and behavioural questions in English or siSwati, and provide written informed consent were eligible for the study. We performed rapid HIV testing and assessed sociodemographic and behavioural characteristics with use of a questionnaire at baseline and, for HIV-seronegative individuals, 6 months later. We calculated HIV incidence with Poisson regression modelling as events per person-years × 100, and we assessed covariables as predictors with Cox proportional hazards modelling. Survey weighting was applied and all models used survey sampling methods., Findings: Between Dec 10, 2010, and June 25, 2011, 11 897 HIV-seronegative adults were enrolled in SHIMS and 11 232 (94%) were re-tested. Of these, 145 HIV seroconversions were observed, resulting in a weighted HIV incidence of 2·4% (95% CI 2·1-2·8). Incidence was nearly twice as high in women (3·1%; 95% CI 2·6-3·7) as in men (1·7%; 1·3-2·1, p<0·0001). Among men, partner's HIV-positive status (adjusted hazard ratio [aHR] 2·67, 1·06-6·82, p=0·040) or unknown serostatus (aHR 4·64, 2·32-9·27, p<0·0001) in the past 6 months predicted HIV seroconversion. Among women, significant predictors included not being married (aHR 2·90, 1·44-5·84, p=0·0030), having a spouse who lives elsewhere (aHR 2·66, 1·29-5·45, p=0·0078), and having a partner in the past 6 months with unknown HIV status (aHR 2·87, 1·44-5·84, p=0·0030)., Interpretation: Swaziland has the highest national HIV incidence in the world. In high-prevalence countries, population-based incidence measures and programmes that further expand HIV testing and support disclosure of HIV status are needed., Funding: President's Emergency Plan for AIDS Relief (PEPFAR) by the Centers for Disease Control and Prevention., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥ 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment., Design: A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012., Methods: Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥ 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission., Results: Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥ 1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter., Conclusions: A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

Background: Gaps in the HIV care continuum contribute to suboptimal individual health outcomes and increased risk of HIV transmission at the population level. Implementation science studies are needed to evaluate clinic-based interventions aimed at improving retention of patients across the continuum., Methods/design: Link4Health uses an unblended cluster site-randomized design to evaluate the effectiveness of a combination intervention strategy (CIS) as compared to standard of care on linkage to and retention in care among HIV-diagnosed adults in Swaziland. The CIS intervention targets a multiplicity of structural, behavioral, and biomedical barriers through five interventions: (1) point-of-care CD4 testing at time of HIV testing, (2) accelerated antiretroviral therapy (ART) initiation for eligible patients, (3) mobile phone appointment reminders, (4) care and prevention packages, and (5) non-cash financial incentives for linkage and retention. The unit of randomization is a network of HIV clinics inclusive of a secondary facility coupled with an affiliated primary facility. Ten study units were randomized based on implementing partner, geographic location, and historic volume of HIV patients. Target enrollment was 2200 individuals, each to be followed for 12 months. Eligibility criteria includes HIV-positive test, age >18 years, willing to receive HIV care at a clinic in the study unit and consent to study procedures. Exclusion criteria included previous HIV care in the past 6 months, planning to leave the community, and current pregnancy. The primary study outcome is linkage within 1 month and retention at 12 months after testing HIV positive. Secondary outcomes include viral load suppression at 12 months, time to ART eligibility and initiation, participant acceptability, and cost-effectiveness. The trial status is that study enrollment is complete and follow-up procedures are ongoing., Discussion: Link4Health evaluates a novel and pragmatic combination intervention strategy to improve linkage to and retention in care among adults with HIV in Swaziland. If the strategy is found to be effective, this study has the potential to inform HIV service delivery in resource-limited settings., Trial Registration: Clinicaltrials.gov NCT01904994.