Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Accuracy of Determine TB-LAM Ag to detect TB in HIV infected patients associated with diagnostic methods used in Brazilian public health units.

BACKGROUND: Determine TB-LAM Ag (LAM) is a point of care test developed to diagnose tuberculosis (TB). The aim of this study was to evaluate the diagnostic performance of LAM in people living with HIV using Brazilian public health network algorithm for TB diagnosis. METHODS AND FINDINGS: A cross-sectional study design was used to enroll 199 adult patients in two sites in Rio de Janeiro and two in São Paulo. The study enrolled HIV-infected patients with CD4 counts ≤200 cells/mm3 (in the Alere PIMA CD4 assay at study screening), patients coughing for at least 2 weeks or presenting a chest radiography suggestive of TB. LAM, in conjunction with sputum smear microscopy or Xpert MTB/RIF (Xpert) as compared to Mycobacterium tuberculosis culture, which was used as a reference standard. TB prevalence was 24.6%. Overall accuracy of LAM was 79.9% (73.8%-84.9%), positive and negative predictive values were 62.2% (46.1%-75.9%) and 84% (77.5%-88.8%), respectively. The overall LAM sensitivity was 46.9% (33.7%-60.6%) and specificity was 90.7% (84.9%-94.4%). The best performance of LAM was observed among patients with CD4 counts ≤50 cells/mm3 (sensitivity = 70.4% and specificity = 85.9%). When 2 respiratory smears were used in conjunction with LAM, sensitivity increased 22%, as compared to just 2 smears. Furthermore, LAM when used in conjunction with two respiratory smears, was as sensitive as compared to a single one. However, no improvement in TB diagnosis occurred when LAM was used with Xpert as compared to Xpert alone. Among 14 LAM false positive tests, Non-Tuberculosis Mycobacteria were isolated in three cases. CONCLUSION: LAM is a point of care test that increased TB diagnosis in immunosuppressed HIV-infected patients when used in conjunction with smear microscopy, but not when used with Xpert in Brazilian public health network sites. Use of LAM test should be considered in settings where immunosuppressed HIV patients need rapid TB diagnosis.

Factors associated with loss to clinic among HIV patients not yet known to be eligible for antiretroviral therapy (ART) in Mozambique.

INTRODUCTION: Retention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been well-characterized. METHODS: We examined data on 37,352 adult pre-ART patients (ART ineligible or unknown eligibility) who enrolled in care during 2005-2008 with >1 clinical visit at 23 clinics in Mozambique. We defined loss to clinic (LTC) as >12 months since the last visit among those not known to have died/transferred. Cox proportional-hazards models were used to examine factors associated with LTC, accounting for clustering within sites. RESULTS: Of 37,352 pre-ART patients, 61% had a CD4 count within three months of enrolment (median CD4: 452, IQR: 345-611). 17,598 (47.1%) were ART ineligible and 19,754 (52.9%) were of unknown eligibility status at enrolment because of missing information on CD4 count and/or WHO stage. Kaplan-Meier estimates for LTC at 12 months were 41% (95% CI: 40.2-41.8) and 48% (95% CI: 47.2-48.8), respectively. Factors associated with LTC among ART ineligible patients included male sex (AHR(men_vs_non-pregnant women): 1.5; 95% CI: 1.4-1.6) and being pregnant at enrolment (AHR(pregnant_vs_non-pregnant women): 1.3; 95% CI: 1.1-1.5). Older age, more education, higher weight and more advanced WHO stage at enrolment were independently associated with lower risks of LTC. Similar findings were observed among patients whose ART eligibility status was unknown at enrolment. CONCLUSIONS: Substantial LTC occurred prior to ART initiation among patients not yet known to be eligible for ART, including nearly half of patients without documented ART eligibility assessment. Interventions are needed to target pre-ART patients who may be at higher risk for LTC, including pregnant women and patients with less advanced HIV disease.

Factors associated with late antiretroviral therapy initiation among adults in Mozambique.

BACKGROUND: Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission. METHODS: To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count<100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation. RESULTS: The proportion of patients initiating ART late decreased from 46% to 37% during 2005-2007, but remained constant (between 37-33%) from 2007-2009. Of those who initiated ART late (median CD4 = 57 cells/µL), 5% were known to have died and 54% were lost to clinic within 6 months of ART initiation (compared with 2% and 47% among other patients starting ART [median CD4 = 192 cells/µL]). In multivariate analysis, female sex and pregnancy at ART initiation (AOR(female_not_pregnant_vs._male) = 0.66, 95%CI [0.62-0.69]; AOR(pregnant_vs._non_pregnant) = 0.60, 95%CI [0.49-0.73]), younger and older age (AOR(15-25_vs.26-30) = 0.86, 95%CI [0.79-0.94], AOR(>45_vs.26-30) = 0.72, 95%CI [0.67-0.77]), entry into care via PMTCT (AOR(entry_through_PMTCT_vs.VCT) = 0.42, 95%CI [0.35-0.50]), marital status (AOR(married/in union_vs.single) = 0.87, 95%CI [0.83-0.92]), education (AOR(secondary_or_higher_vs.primary) = 0.87, 95%CI [0.83-0.93]) and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AOR(CD4_machine_onsite_vs.offsite) = 0.83, 95%CI [0.74-0.94]) and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77-0.93]). CONCLUSION: The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.

Factors Associated with Late Antiretroviral Therapy Initiation among Adults in Mozambique

Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission. To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count<100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation. The proportion of patients initiating ART late decreased from 46% to 37% during 2005­2007, but remained constant (between 37­33%) from 2007­2009. Of those who initiated ART late (median CD4 = 57 cells/µL), 5% were known to have died and 54% were lost to clinic within 6 months of ART initiation (compared with 2% and 47% among other patients starting ART [median CD4 = 192 cells/µL]). In multivariate analysis, female sex and pregnancy at ART initiation (AORfemale_not_pregnant_vs._male = 0.66, 95%CI [0.62­0.69]; AORpregnant_vs._non_pregnant = 0.60, 95%CI [0.49­0.73]), younger and older age (AOR15­25_vs.26­30 = 0.86, 95%CI [0.79­0.94], AOR>45_vs.26­30 = 0.72, 95%CI [0.67­0.77]), entry into care via PMTCT (AORentry_through_PMTCT_vs.VCT = 0.42, 95%CI [0.35­0.50]), marital status (AORmarried/in union_vs.single = 0.87, 95%CI [0.83­0.92]), education (AORsecondary_or_higher_vs.primary = 0.87, 95%CI [0.83­0.93]) and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AORCD4_machine_onsite_vs.offsite = 0.83, 95%CI [0.74­0.94]) and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77­0.93]). The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.

Patients enrolled in HIV care in Mozambique: baseline characteristics and follow-up outcomes.

OBJECTIVE: To utilize routinely collected service delivery data from HIV care and treatment clinics in Mozambique to describe the patient population and programmatic outcomes from 2003 to 2009. METHODS: Data from patient charts were entered into an electronic database at 28 clinics in 5 Mozambican provinces. Patients' characteristics at enrollment in HIV care and at antiretroviral therapy (ART) initiation were examined. We calculated a corrected 12-month mortality estimate using a recently developed nomogram for sub-Saharan African ART patients. RESULTS: A total of 154,188 HIV-infected individuals (10,164 children <15 years old) were enrolled in HIV care services between 2003 and 2009. Of the 51,269 (36%) adults who started ART, 35% initiated ART with CD4 count <100 cells per microliter and 14.4% with World Health Organization stage IV. Just more than 10% (10.5%) of women were documented to be pregnant at enrollment. One-third of the 3,745 (37%) children who initiated ART were <2 years old, and 53% of those <5 years initiated ART severely immunosuppressed (CD4% <15%). Thirty-five percent of all children and 30% of those initiating ART met the definition of severe malnourishment (weight-for-age Z score <-3). Among those who initiated ART, the median estimated 12-month mortality rate across sites was 13.1% (interquartile range: 11.5%-16.0%) and 13.5% (interquartile range: 11.4%-17.4%) for adults and children, respectively. CONCLUSIONS: A substantial number of HIV-infected patients have been enrolled in HIV care and initiated on ART, with many patients having advanced HIV disease. With the release of new guidelines for ART use for adults, pregnant women, and children, extensive efforts are needed to ensure more timely initiation of ART.

Chagas' disease and HIV co-infection in patients without effective antiretroviral therapy: prevalence, clinical presentation and natural history.

The objectives of this study were to establish the prevalence of Chagas' disease among HIV seropositive patients and to define the clinical profile of co-infected cases. Cross-sectional study: the prevalence of co-infected subjects was 1.3% and there was no significant difference between co-infected and non co-infected patients relative to race, birthplace, home address and CD4 T cells. The co-infected group comprised predominantly women and mean age and median viral load were higher. Longitudinal study: included 20 patients (12 women) and described the clinical presentation and natural history of concomitant infections. The mean follow-up time was 35.8 months, mean age was 43+/-8.7 years and 60% of patients were white. During the follow-up, a total of 113 serological tests for Chagas' disease were performed: 89 (78.8%) were reactive/positive, 21 (18.6%) were doubtful and three (2.6%) were non-reactive/negative. Positive results for xenodiagnosis were high (81%). At the baseline evaluation, thirteen patients had the indeterminate form of Chagas' disease and seven cardiopathy. One patient developed from indeterminate to digestive form, three had a reactivation of Chagas' disease in the central nervous system, all had parasitological confirmation and received specific treatment. There were 11 deaths. Thus, HIV-infected patients should be tested for Chagas' disease when epidemiologically relevant.

Inquérito sorológico para a infecção por Toxoplasma gondii em ameríndios isolados, Mato Grosso / Serological survey of Toxoplasma gondii infection in isolated Amerindians, Mato Grosso

Este estudo determinou a ocorrência de anticorpos anti-Toxoplasma gondii em população indígena do Mato Grosso, os Enawenê-Nawê. Estes habitam uma vasta região selvagem, com raros contatos com não-índios. Não apresentam animais domésticos, inclusive gatos. A dieta é baseada em insetos, mandioca, milho, mel e fungos e não se alimentam de carne, exceto de peixe. Com base no exposto, desenvolveu-se análise sorológica, por meio de ELISA - IgG e IFI - IgG e IgM. De 148 soros, 80,4 por cento foram ELISA ou IFI- IgG positivos. Não foram detectados casos de IgM reagentes. Nesse grupo as taxas de soropositividade aumentaram significativamente com a idade, de 50 por cento a 95 por cento. Analisando-se os hábitos e costumes, aliados à alta soropositividade encontrada, sugere-se que a presença de felinos silvestres nas imediações da aldeia e coleções de água poderia ter papel importante como fonte de infecção, contaminando o solo e, conseqüentemente, os insetos e fungos consumidos pelos índios.

[Serological survey of Toxoplasma gondii infection in isolated Amerindians, Mato Grosso]. / Inquérito sorológico para a infecção por Toxoplasma gondii em ameríndios isolados, Mato Grosso.

This study determined the occurrence of the antibodies anti-Toxoplasma gondii among the Enawenê-Nawê, an indigenous population of Mato Grosso. These inhabit a vast wild area, with rare contacts with non-Indians. They do not keep domestic animals, including cats. Their diet is based on insects, cassava, corn, honey and mushrooms, they do not consume meat, except fish. Based on the above, serologic tests ELISA-IgG and indirect fluorescent antibody test for IgG/IgM were performed. From 148 samples, 80.4% positive for IgG by ELISA or indirect fluorescent antibody test. No IgM reagent cases were detected. In that group the seropositivity rates increased significantly with age from 50% to 95%. Having analyzed their customs and habits, together with the high seropositivity found, it is suggested that the presence of wild felines in the vicinity of the village and areas where water collects could play an important role as an infection source, contaminating soil and consequently insects and mushrooms consumed by the Indians.

Listeriosis and AIDS: case report and literature review

Listeriosis is a not uncommon infection in humans, usually associated with immunodeficient states and with newborns. However, relatively few cases have been reported in HIV-infected patients. This scarcity of reported cases has aroused interest in the association of listeriosis and AIDS. In this paper we present a case of meningitis and septicemia caused by Listeria monocytogenes in a female patient with AIDS. A review of recent medical literature indicates that association of listeriosis and AIDS may be more common than it seems. Recent research in host-parasite interaction in listerial infection suggests an important role for tumor necrosis factor (TNF) and for integralin, a bacterial protein, in modulating listerial disease in AIDS patients. Inadequate diagnosis may be in part responsible for the scarcity of reports