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Access to care is essential for people with HIV (PWH) but may have been affected during the COVID-19 pandemic. We conducted a retrospective cross-sectional study of adult PWH receiving care in a large southeastern comprehensive care clinic in the United States. Patients in care between January 1, 2017, and July 30, 2020, were included. Race/ethnicity, sex, HIV-1 RNA, CD4 + lymphocyte count were included as baseline covariates. Outcomes included clinic attendance, receipt of HIV-1 RNA PCR testing, and virologic suppression (HIV-1 RNA < 200 copies/mL); outpatient encounters included new patient encounters, follow-up visits, and mental health encounters. Total medical encounters, including telemedicine, decreased by 827 visits (33%) when comparing the second quarters of 2019 and 2020. New patient encounters decreased by 23.5% from 81 to 62 during this period. The second quarter of 2020 saw the lowest number of new patient visits since 2017. HIV-1 RNA testing and the proportion of patients with virologic suppression decreased during the pandemic (p < 0.001 for both). Total mental health encounters, on the other hand, increased by 14% during April-June 2020 compared to April-June 2019. Mental health electronic communications increased by 60% from 312 to 500 during the same period, with a 20% increase in medication refills. The COVID-19 pandemic affected outpatient visits, viral load surveillance, and virologic suppression but led to an increase in mental health encounters in a comprehensive care clinic setting.

Across rural sub-Saharan Africa, people living with HIV (PLHIV) commonly seek out treatment from traditional healers. We report on the clinical outcomes of a community health worker intervention adapted for traditional healers with insight into our results from qualitative interviews. We employed a pre-post intervention study design and used sequential mixed methods to assess the impact of a traditional healer support worker intervention in Zambézia province, Mozambique. After receiving a positive test result, 276 participants who were newly enrolled in HIV treatment and were interested in receiving home-based support from a traditional healer were recruited into the study. Those who enrolled from February 2016 to August 2016 received standard of care services, while those who enrolled from June 2017 to May 2018 received support from a traditional healer. We conducted interviews among healers and participants to gain insight into fidelity of study activities, barriers to support, and program improvement. Medication possession ratio at home (based on pharmacy pick-up dates) was not significantly different between pre- and post-intervention participants (0.80 in the pre-intervention group compared to 0.79 in the post-intervention group; p = 0.96). Participants reported receiving educational and psychosocial support from healers. Healers adapted their support protocol to initiate directly observed therapy among participants with poor adherence. Traditional healers can provide community-based psychosocial support, education, directly observed therapy, and disclosure assistance for PLHIV. Multiple factors may hinder patients’ desire and ability to remain adherent to treatment, including poverty, confusion about medication side effects, and frustration with wait times at the health facility.

Updated World Health Organization (WHO) treatment guidelines prioritize all-oral drug-resistant tuberculosis (DR-TB) regimens. Several poorly tolerated drugs, such as amikacin and para-aminosalicylic acid (PAS), remain treatment options for DR-TB in WHO-recommended longer regimens as Group C drugs. Incomplete treatment with anti-TB drugs increases the risk of treatment failure, relapse, and death. We determined whether missed doses of individual anti-TB drugs, and reasons for their discontinuation, varied in closely monitored hospital settings prior to the 2020 WHO DR-TB treatment guideline updates. We collected retrospective data on adult patients with microbiologically confirmed DR-TB between 2008 and 2015 who were selected for a study of acquired drug resistance in the Western Cape Province of South Africa. Medical records through mid-2017 were reviewed. Patients received directly observed treatment during hospitalization at specialized DR-TB hospitals. Incomplete treatment with individual anti-TB drugs, defined as the failure to take medication as prescribed, regardless of reason, was determined by comparing percent missed doses, stratified by HIV status and DR-TB regimen. We applied a generalized mixed effects model. Among 242 patients, 131 (54%) were male, 97 (40%) were living with HIV, 175 (72%) received second-line treatment prior to first hospitalization, and 191 (79%) died during the study period. At initial hospitalization, 134 (55%) patients had Mycobacterium tuberculosis with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]) without resistance to ofloxacin or amikacin, and 102 (42%) had resistance to ofloxacin and/or amikacin. Most patients (129 [53%]) had multiple hospitalizations and DST changes occurred in 146 (60%) by the end of their last hospital discharge. Incomplete treatment was significantly higher for amikacin (18%), capreomycin (18%), PAS (17%) and kanamycin (16%) than other DR-TB drugs (P<0.001), including ethionamide (8%), moxifloxacin (7%), terizidone (7%), ethambutol (7%), and pyrazinamide (6%). Among the most frequently prescribed drugs, second-line injectables had the highest rates of discontinuation for adverse events (range 0.56-1.02 events per year follow-up), while amikacin, PAS and ethionamide had the highest rates of discontinuation for patient refusal (range 0.51-0.68 events per year follow-up). Missed doses did not differ according to HIV status or anti-TB drug combinations. We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed.

We assessed trends and identified individual- and county-level factors associated with individual linkage to HIV care in Tennessee (TN). TN residents diagnosed with HIV from 2012-2016 were included in the analysis (n = 3,751). Individuals were assigned county-level factors based on county of residence at the time of diagnosis. Linkage was defined by the first CD4 or HIV RNA test date after HIV diagnosis. We used modified Poisson regression to estimate probability of 30-day linkage to care at the individual-level and the contribution of individual and county-level factors to this outcome. Both MSM (aRR 1.23, 95%CI 0.98-1.55) and women who reported heterosexual sex risk factors (aRR 1.39, 95%CI 1.18-1.65) were more likely to link to care within 30-days than heterosexual males. Non-Hispanic Black individuals had poorer linkage than White individuals (aRR 0.77, 95%CI 0.71-0.83). County-level mentally unhealthy days were negatively associated with linkage (aRR 0.63, 95%CI: 0.40-0.99). Racial disparities in linkage to care persist at both individual and county levels, even when adjusting for county-level social determinants of health. These findings suggest a need for structural interventions to address both structural racism and mental health needs to improve linkage to care and minimize racial disparities in HIV outcomes.

A growing population of older adults with HIV will increase demands on HIV-related healthcare. Nearly a quarter of people receiving care for HIV in Latin America are currently 50 years or older, yet little is known about the frequency of comorbidities in this population. We estimated the prevalence and incidence of non-communicable diseases (NCDs) among people 50 years of age or older (≥50yo) receiving HIV care during 2000-2015 in six centers affiliated with the Caribbean, Central and South American network for HIV epidemiology (CCASAnet). We estimated the annual prevalence, and overall prevalence and incidence of cardiovascular diseases, diabetes, hypertension, dyslipidemia, psychiatric disorders, chronic liver and renal diseases, and non-AIDS-defining cancers, and multimorbidity (more than one NCD) of people ≥50yo receiving care for HIV. Analyses were performed according to age at enrollment into HIV care (<50yo and ≥50yo). We included 3,415 patients ≥50yo, of whom 1,487(43%) were enrolled at age ≥50 years. The annual prevalence of NCDs increased from 32% to 68% and multimorbidity from 30% to 40% during 2000-2015. At the last registered visit, 53% of patients enrolled <50yo and 50% of those enrolled ≥50yo had at least one NCD. Most common NCDs at the last visit in each age-group at enrollment were dyslipidemia (36% in <50yo and 28% in ≥50yo), hypertension (17% and 18%), psychiatric disorders (15% and 10%), and diabetes (11% and 12%). The prevalence of NCDs and multimorbidity in people ≥50 years receiving care for HIV in CCASAnet centers in Latin America increased substantially in the last 15 years. Our results make evident the need of planning for provision of complex, primary care for aging adults living with HIV.

Introduction Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non‐AIDS‐related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long‐term follow‐up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all‐cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. Methods Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug‐based combination therapy and with medical follow‐up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T‐cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3). Primary outcomes included all‐cause mortality, AIDS‐defining events and non‐communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T‐cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. Results In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow‐up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T‐cell count) and older age were risk factors for all‐cause mortality. We also found that older age, male sex and higher baseline CD4 T‐cell count were associated with lower CD4 count increase following therapy initiation. Conclusions Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow‐up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

Residents of Zambézia Province, Mozambique live from rural subsistence farming and fishing. The 2009 provincial HIV prevalence for adults 15-49 years was 12.6%, higher among women (15.3%) than men (8.9%). We reviewed clinical data to assess outcomes for HIV-infected children on combination antiretroviral therapy (cART) in a highly resource-limited setting. We studied rates of 2-year mortality and loss to follow-up (LTFU) for children <15 years of age initiating cART between June 2006-July 2011 in 10 rural districts. National guidelines define LTFU as >60 days following last-scheduled medication pickup. Kaplan-Meier estimates to compute mortality assumed non-informative censoring. Cumulative LTFU incidence calculations treated death as a competing risk. Of 753 children, 29.0% (95% CI: 24.5, 33.2) were confirmed dead by 2 years and 39.0% (95% CI: 34.8, 42.9) were LTFU with unknown clinical outcomes. The cohort mortality rate was 8.4% (95% CI: 6.3, 10.4) after 90 days on cART and 19.2% (95% CI: 16.0, 22.3) after 365 days. Higher hemoglobin at cART initiation was associated with being alive and on cART at 2 years (alive: 9.3 g/dL vs. dead or LTFU: 8.3-8.4 g/dL, p<0.01). Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes Treatment was initiated late (WHO stage III/IV) among 48% of the children with WHO stage recorded in their records. Marked heterogeneity in outcomes by district was noted (p<0.001). We found poor clinical and programmatic outcomes among children taking cART in rural Mozambique. Expanded testing, early infant diagnosis, counseling/support services, case finding, and outreach are insufficiently implemented. Our quality improvement efforts seek to better link pregnancy and HIV services, expand coverage and timeliness of infant diagnosis and treatment, and increase follow-up and adherence.

There are few studies that characterize sex-related differences in HIV outcomes among adolescents and young adults (AYA) 15-24 years of age. We conducted a retrospective cohort study among AYA who enrolled in a comprehensive HIV program in Mozambique between 2012-2016. We assessed patients by sex and pregnancy/lactation status, comparing time to combination antiretroviral therapy (ART) initiation using Cox proportional hazard models. We employed multivariable logistic regression to investigate pre- and post-ART retention. Patients were defined as 'retained pre-ART' if they attended at least 3 of 4 required visits or started ART in the 6 months after enrollment, and 'retained post-ART' if they had any ART pickup or clinical visit during the last 90 days of the one-year follow-up period. Of 47,702 patients in the cohort, 81% (n = 38,511) were female and 19% (n = 9,191) were male. Of the females, 57% (n = 21,770) were non-pregnant and non-lactating (NPNL) and 43% (n = 16,741) were pregnant or lactating (PL). PL (aHR 2.64, 95%CI:2.47-2.81) and NPNL females (aHR 1.36, 95%CI:1.30-1.42) were more likely to initiate ART than males. PL females had higher odds of pre-ART retention in care (aOR 3.56, 95%CI: 3.30-3.84), as did NPNL females (aOR 1.71, 95%CI: 1.62-1.81), compared to males. This was also true for retention post-ART initiation, with higher odds for both PL (aOR 1.78, 95%CI:1.63-1.94) and NPNL females (aOR 1.50, 95%CI:1.35-1.65) compared to males. PL females were most likely to initiate ART and remain in care post-ART in this AYA cohort, likely reflecting expansion of Option B+. Despite pregnancy and policy driven factors, we observed important sex-related disparities in this cohort. NPNL females were more likely to initiate ART and be retained in care before and after ART initiation than males. These data suggest that young males need targeted interventions to improve these important care continuum outcomes.

In the absence of stand-alone infrastructures for delivering cervical cancer screening services, efforts are underway in sub-Saharan Africa to dovetail screening with ongoing vertical health initiatives like HIV/AIDS care programs. Yet, evidence demonstrating the utilization of cervical cancer prevention services in such integrated programs by women of the general population is lacking. We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia (CCPPZ), the largest public sector programs of its kind in sub-Saharan Africa. We evaluated patterns of utilization of screening services by HIV serostatus, examined contemporaneous trends in screening outcomes, and used multivariable modeling to identify factors associated with screening test positivity. Between January 2006 and April 2011, CCPPZ services were utilized by 56,247 women who underwent cervical cancer screening with visual inspection with acetic acid (VIA), aided by digital cervicography. The proportion of women accessing these services who were HIV-seropositive declined from 54% to 23% between 2006-2010, which coincided with increasing proportions of HIV-seronegative women (from 22% to 38%) and women whose HIV serostatus was unknown (from 24% to 39%) (all p-for trend<0.001). The rates of VIA screening positivity declined from 47% to 17% during the same period (p-for trend <0.001), and this decline was consistent across all HIV serostatus categories. After adjusting for demographic and sexual/reproductive factors, HIV-seropositive women were more than twice as likely (Odds ratio 2.62, 95% CI 2.49, 2.76) to screen VIA-positive than HIV-seronegative women. This is the first 'real world' demonstration in a public sector implementation program in a sub-Saharan African setting that with successful program scale-up efforts, nurse-led cervical cancer screening programs targeting women with HIV can expand and serve all women, regardless of HIV serostatus. Screening program performance can improve with adequate emphasis on training, quality control, and telemedicine-support for nurse-providers in clinical decision making.

Regression models for continuous outcomes frequently require a transformation of the outcome, which is often specified a priori or estimated from a parametric family. Cumulative probability models (CPMs) nonparametrically estimate the transformation by treating the continuous outcome as if it is ordered categorically. They thus represent a flexible analysis approach for continuous outcomes. However, it is difficult to establish asymptotic properties for CPMs due to the potentially unbounded range of the transformation. Here we show asymptotic properties for CPMs when applied to slightly modified data where bounds, one lower and one upper, are chosen and the outcomes outside the bounds are set as two ordinal categories. We prove the uniform consistency of the estimated regression coefficients and of the estimated transformation function between the bounds. We also describe their joint asymptotic distribution, and show that the estimated regression coefficients attain the semiparametric efficiency bound. We show with simulations that results from this approach and those from using the CPM on the original data are very similar when a small fraction of the data are modified. We reanalyze a dataset of HIV-positive patients with CPMs to illustrate and compare the approaches.