Facility-Level Factors Influencing Retention of Patients in HIV Care in East Africa

Losses to follow-up (LTFU) remain an important programmatic challenge. While numerous patient-level factors have been associated with LTFU, less is known about facility-level factors. Data from the East African International epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium was used to identify facility-level factors associated with LTFU in Kenya, Tanzania and Uganda. Patients were defined as LTFU if they had no visit within 12 months of the study endpoint for pre-ART patients or 6 months for patients on ART. Adjusting for patient factors, shared frailty proportional hazard models were used to identify the facility-level factors associated with LTFU for the pre- and post-ART periods. Data from 77,362 patients and 29 facilities were analyzed. Median age at enrolment was 36.0 years (Interquartile Range: 30.1, 43.1), 63.9% were women and 58.3% initiated ART. Rates (95% Confidence Interval) of LTFU were 25.1 (24.7-25.6) and 16.7 (16.3-17.2) per 100 person-years in the pre-ART and post-ART periods, respectively. Facility-level factors associated with increased LTFU included secondary-level care, HIV RNA PCR turnaround time >14 days, and no onsite availability of CD4 testing. Increased LTFU was also observed when no nutritional supplements were provided (pre-ART only), when TB patients were treated within the HIV program (pre-ART only), and when the facility was open ≤4 mornings per week (ART only). Our findings suggest that facility-based strategies such as point of care laboratory testing and separate clinic spaces for TB patients may improve retention

CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517-541] in North America, 494/µl (95% CI: 429-559) in West Africa, 515/µl (95% CI: 508-522) in Southern Africa, 503/µl (95% CI: 478-528) in Asia and 437/µl (95% CI: 425-449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional leve

Retention in Care and Connection to Care among HIV-Infected Patients on Antiretroviral Therapy in Africa: Estimation via a Sampling-Based Approach

Current estimates of retention among HIV-infected patients on antiretroviral therapy (ART) in Africa consider patients who are lost to follow-up (LTF) as well as those who die shortly after their last clinic visit to be no longer in care and to represent limitations in access to care. Yet many lost patients may have "silently" transferred and deaths shortly after the last clinic visit more likely represent limitations in clinical care rather than access to care after initial linkage.We evaluated HIV-infected adults initiating ART from 1/1/2004 to 9/30/2007 at a clinic in rural Uganda. A representative sample of lost patients was tracked in the community to obtain updated information about care at other ART sites. Updated outcomes were incorporated with probability weights to obtain "corrected" estimates of retention for the entire clinic population. We used the competing risks approach to estimate "connection to care"--the percentage of patients accessing care over time (including those who died while in care).Among 3,628 patients, 829 became lost, 128 were tracked and in 111, updated information was obtained. Of 111, 79 (71%) were alive and 35/48 (73%) of patients interviewed in person were in care and on ART. Patient retention for the clinic population assuming lost patients were not in care was 82.3%, 68.9%, and 60.1% at 1, 2 and 3 years. Incorporating updated care information from the sample of lost patients increased estimates of patient retention to 85.8% to 90.9%, 78.9% to 86.2% and 75.8% to 84.7% at the same time points.Accounting for "silent transfers" and early deaths increased estimates of patient retention and connection to care substantially. Deaths soon after the last clinic visit (potentially reflecting limitations in clinical effectiveness) and disconnection from care among patient who were alive each accounted for approximately half of failures of retention

AIDS alters the commensal plasma virome.

We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses

Sexually transmitted infection (STI) knowledge and perceptions among people in HIV-sero-different partnerships in rural southwestern Uganda.

Globally, over one million people acquire curable sexually transmitted infections (STI) each day. Understanding how people think about STIs is key to building culturally appropriate STI prevention and treatment programs. We explored STI knowledge and perceptions in rural, southwestern Uganda to inform future interventions. From August 2020 to December 2020, we conducted individual in-depth interviews among adult men and women (≥18 years) with recent or current personal or partner pregnancy, a history of an STI diagnosis and treatment, and membership in an HIV-sero-different relationship. Interviews explored STI knowledge, perceptions, and barriers and facilitators to engaging in STI care. We used inductive and deductive approaches to generate a codebook guided by the healthcare literacy skills framework in a thematic analysis. Ten men with STI, five of their female partners, eighteen women with STI, and four of their male partners participated in individual in-depth interviews. The median age was 41 (range 27-50) for men and 29 (range 22-40) for women. Sixteen (43%) participants were with HIV. Significant themes include: 1) Participants obtained STI knowledge and information from the community (friends, family members, acquaintances) and medical professionals; 2) While participants knew STIs were transmitted sexually, they also believed transmission occurred via non-sexual mechanisms. 3) Participants associated different connotations and amounts of stigma with each STI, for example, participants reported that syphilis was passed down "genetically" from parent to child. 4) Participants reported uncertainty about whether STIs affected pregnancy outcomes and whether antenatal STI treatment was safe. The complicated nature of STIs has led to understandable confusion in settings without formal sexual healthcare education. Robust counseling and education prior to sexual debut will help allow men and women to understand the signs, symptoms, and treatments necessary for STI cure and to navigate often complicated and overburdened healthcare systems

Brief Report: The Impact of Disease Stage on Early Gaps in ART in the treatment for All Era - A Multisite Cohort Study.

Adoption of Treat All policies has increased ART initiation in sub-Saharan Africa; however, unexplained early losses continue to occur. More information is needed to understand why treatment discontinuation continues at this vulnerable stage in care

Variation in Hiv-1 Nef Function Within and Among Viral Subtypes Reveals Genetically Separable Antagonism of Serinc3 and Serinc5

HIV Nef counteracts cellular host restriction factors SERINC3 and SERINC5, but our understanding of how naturally occurring global Nef sequence diversity impacts these activities is limited. Here, we quantify SERINC3 and SERINC5 internalization function for 339 Nef clones, representing the major pandemic HIV-1 group M subtypes A, B, C and D. We describe distinct subtype-associated hierarchies for Nef-mediated internalization of SERINC5, for which subtype B clones display the highest activities on average, and of SERINC3, for which subtype B clones display the lowest activities on average. We further identify Nef polymorphisms that modulate its ability to counteract SERINC proteins, including substitutions in the N-terminal domain that selectively impair SERINC3 internalization. Our findings demonstrate that the SERINC antagonism activities of HIV Nef differ markedly among major viral subtypes and between individual isolates within a subtype, suggesting that variation in these functions may contribute to global differences in viral pathogenesis

Internalized Stigma, Depressive Symptoms, and the Modifying Role of Antiretroviral Therapy: A Cohort Study in Rural Uganda

Depression affects over 40% of people with HIV (PHIV) in low- and middle-income countries, and over half of PHIV report HIV-related internalized stigma. However, few longitudinal studies of PHIV have examined the relationship between HIV-related stigma and depression. Data were analyzed from the 2007-15 Uganda AIDS Rural Treatment Outcomes (UARTO) Study, a cohort of 454 antiretroviral therapy (ART)-naïve PHIV (68% women) starting ART. Our primary outcome was depression symptom severity over the first two years of ART, measured using a locally adapted version of the Hopkins Symptom Checklist; our primary exposure was the 6-item Internalized AIDS-Related Stigma Scale. Both scores were measured at enrollment and at quarterly follow-up visits. We fit linear generalized estimating equations (GEE) regression models to estimate the association between stigma and depression symptom severity, adjusting for potential confounders. We included a stigma × time product term to assess the modifying effect of ART on the association between internalized stigma and depression symptom severity. UARTO participants had a median age of 32 years and median enrollment CD4 count of 217 cells/mm3. Both depression symptom severity and internalized stigma declined on ART, particularly during the first treatment year. In multivariable regression models, depression symptom severity was positively associated with internalized stigma (b = 0.03; 95% confidence interval [CI], 0.02 to 0.04) and negatively associated with ART duration \u3e6 months (b = −0.16; 95% CI, −0.19 to −0.13). The estimated product term coefficient was negative and statistically significant (P = 0.004), suggesting that the association between internalized stigma and depression symptom severity weakened over time on ART. Thus, in this large cohort of PHIV initiating ART in rural Uganda, depression symptom severity was associated with internalized stigma but the association declined with time on ART. These findings underscore the potential value of ART as a stigma reduction intervention for PHIV, particularly during early treatment

Sexually Transmitted Infection Prevalence among Women at Risk for HIV Exposure Initiating Safer Conception Care in Rural, Southwestern Uganda

Background Knowledge of sexually transmitted infection (STI) prevalence and risk factors is important to the development of tenofovir-based preexposure prophylaxis (PrEP) and safer conception programming. We introduced STI screening among women at risk for HIV exposure who were participating in a safer conception study in southwestern Uganda. Methods We enrolled 131 HIV-uninfected women, planning for pregnancy with a partner living with HIV or of unknown HIV serostatus (2018-2019). Women were offered comprehensive safer conception counseling, including PrEP. Participants completed interviewer-administered questionnaires detailing sociodemographics and sexual history. We integrated laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis as a substudy to assess STI prevalence. Multivariable logistic regression was used to determine correlates. Results Ninety-four women completed STI screening (72% of enrolled). Median age was 30 (interquartile range, 26-34) years, and 94% chose PrEP as part of safer conception care. Overall, 24% had STIs: 13% chlamydia, 2% gonorrhea, 6% trichomoniasis, 6% syphilis, and 3% ≥2 STI. Sexually transmitted infection prevalence was associated with younger age (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.77-0.99), prior stillbirth (AOR, 5.04; 95% CI, 1.12-22.54), and not feeling vulnerable to HIV (AOR, 16.33; 95% CI, 1.12-237.94). Conclusions We describe a 24% curable STI prevalence among women at risk for HIV exposure who were planning for pregnancy. These data highlight the importance of integrating laboratory-based STI screening into safer conception programs to maximize the health of HIV-affected women, children, and families