Treatment and comorbidity burden among people living with HIV: a review of systematic literature reviews.

Background: As the human immunodeficiency virus (HIV) treatment landscape continues to evolve, the prolonged life expectancy and long-term exposure to antiretroviral drugs have modified the burden associated with living with HIV. Objective: To better understand the current treatment and comorbidity burden in people living with HIV (PLWH). Methods: Peer-reviewed systematic literature reviews (SLRs) between 2017 and 2020 that included US studies and examined drug adherence/pill burden, resistance burden, or comorbidities in PLWH were identified. Methods and findings were extracted for the overall studies and examined in the subset of US studies. Results: Among 665 publications identified, 47 met the inclusion criteria (drug adherence/pill burden: 5; resistance: 3; comorbidities: 40). While antiretroviral drug adherence levels varied across SLRs, single-tablet regimens (STR) were associated with higher adherence versus multiple-tablet regimens. STRs were also associated with lower risk of treatment discontinuation, higher cost-effectiveness, and lower risk of hospitalization. Longer survival resulted in a high comorbidity burden, with non-AIDS causes accounting for 47% of deaths among PLWH in the US. HIV doubled the risk of cardiovascular disease and was associated with other health problems, including bone and muscle diseases, depression, and cancers. Several antiretroviral regimens were associated with chronic diseases, including cardiometabolic conditions. Lifetime HIV costs are substantially increasing, driven by antiretroviral, adverse event, and comorbidity treatment costs cumulated due to longer survival times. Conclusions: There is a considerable burden associated with HIV and antiretroviral treatment, highlighting the benefits of less complex and safer regimens, and the unmet need for effective preventative interventions.

Brief Report: Intracellular Cystatin B Levels Are Altered in HIV-Infected Participants With Respect to Neurocognitive Status and Antiretroviral Therapy.

ABSTRACT: With advances in HIV treatment, people with HIV (PWH) are living longer but experience aging-related comorbidities, including cognitive deficits, at higher rates than the general population. Previous studies have shown alterations in lysosomal proteins in blood from PWH with severe dementia. However, these markers have not been evaluated in PWH with milder neurocognitive impairment. We sought to determine whether levels of the lysosomal cysteine protease cathepsin B (CatB) and its endogenous inhibitor cystatin B (CysB) were altered in PWH with neurocognitive impairment and whether antiretroviral therapy (ART) further influenced these levels. Peripheral blood mononuclear cells were obtained from the tenofovir arm of a multicenter clinical trial in which ART-naive, HIV+ participants received treatment for 48 weeks (ACTG A5303, NCT01400412). PWH were divided by neurocognitive status (eg, with or without neurocognitive impairment) before ART initiation. Intracellular levels of CatB and CysB were measured in T cells and monocytes by means of flow cytometry. Levels of CysB were significantly decreased in both CD4 + T cells and CD8 + T cells after 48 weeks of ART in HIV+ participants without neurocognitive impairment but not in participants with neurocognitive impairment. Levels of CysB were increased in CD14 + monocytes from the participants with neurocognitive impairment after ART. Levels of CysB and CatB positively correlated regardless of HIV, neurocognitive status, or exposure to ART. These findings suggest that CysB has the potential to provide mechanistic insight into HIV-associated neurocognitive disorders or provide a molecular target for systemic monitoring or treatment of neurocognitive impairment in the context of ART and should be investigated further.

Evaluation of the iCARE Nigeria Pilot Intervention Using Social Media and Peer Navigation to Promote HIV Testing and Linkage to Care Among High-Risk Young Men: A Nonrandomized Controlled Trial.

Importance: Nigeria has the fourth-largest HIV epidemic globally, yet high levels of social stigma inhibit HIV testing among Nigerian youths and young men who have sex with men (MSM). Objective: To report pilot data from iCARE Nigeria (Intensive Combination Approach to Roll Back the Epidemic in Nigerian Adolescents), a combination intervention using social media and peer navigation to promote HIV testing and linkage to care among high-risk youths and young men (hereinafter referred to as young men), including predominantly young MSM. Design, Setting, and Participants: This nonrandomized controlled study assessed an organizational and community-level 12-month, preintervention-postintervention pilot trial of a combination intervention designed to increase HIV testing uptake, increase the rate of identified seropositive cases, and improve linkage to care among young men, including MSM, using social media outreach and peer navigation. Data were collected from June 1, 2019, to May 30, 2020. Participants were young men aged 15 to 24 years in the city of Ibadan, Nigeria, and surrounding areas. Frequencies and percentages were examined, and a Fisher exact test was used to evaluate outcomes compared with historical surveillance data. Linkage to care was defined as 2 clinic visits, including HIV confirmation, within 2 months of a positive rapid test result. Intervention: Four peer navigators conducted social media outreach promoting sexual health and guiding individuals to HIV counseling and rapid testing in clinical, community, or home-based settings. Main Outcomes and Measures: Primary outcomes included the number of young men tested for HIV at university-based iCARE catchment clinics or by iCARE peer navigators in the community, the postintervention HIV seroprevalence of these groups, and linkage to care of participants diagnosed with HIV infection. Results: A total of 339 participants underwent testing for HIV (mean [SD] age, 21.7 [1.9] years), with 283 (83.5%) referred through social media. The main referral sources for social media were WhatsApp (124 [43.8%]), Facebook (101 [35.7%]), and Grindr (57 [20.1%]). Regarding testing location, participants chose home (134 [39.5%]), community-based (202 [59.6%]), or clinic (3 [0.9%]) settings. Eighty-six participants reported no prior HIV testing. Thirty-six participants (10.6%) were confirmed as HIV seropositive; among those, 18 (50.0%) reported negative test results within the past year, and 31 (86.1%) were linked to care. In two 6-month follow-up periods, the intervention increased HIV testing by 42% and 31%, respectively, and seroprevalence increased compared with historical trends with odds ratios of 3.37 (95% CI, 1.43-8.02; P = .002) and 2.74 (95% CI, 1.10-7.11; P = .02), respectively. Conclusions and Relevance: These findings suggest that use of iCARE Nigeria was associated with increased HIV testing and linkage to care in a high-risk, difficult-to-reach population, making it a promising combination intervention for young MSM. Trial Registration: isrctn.org Identifier: ISRCTN94590823.

Rapid HIV Antigen-Antibody Assays and Detection of Acute HIV Infection in Sub-Saharan Africa.

Detection of acute HIV infection is a unique problem that fourth-generation HIV assays were expected to alleviate. In this commentary, we draw attention to the limitations and challenges with use of currently available rapid antigen-antibody (Ag/Ab) combination tests for detection of acute HIV infection in sub-Saharan Africa. Laboratory-based HIV-1 Ag/Ab immunoassays are complex, requiring specialized equipment and handling that are currently not affordable in many settings in Africa. The point-of-care Ag/Ab platform on the other hand is easier to deploy and potentially more accessible in resource-limited settings. However, available fourth-generation HIV-1 rapid diagnostic tests have demonstrated poor performance characteristics in field studies where non-B subtypes of HIV-1 dominate. The potential for point-of-care HIV-1 Ag/Ab diagnostics to significantly improve detection of acute HIV infection remains yet to be realized in sub-Saharan Africa. Assay platforms need to be optimized to identify local circulating subtypes, and optimal algorithms need to be determined.

Plasma Cystatin C Associates With HIV-Associated Neurocognitive Disorder but Is a Poor Diagnostic Marker in Antiretroviral Therapy-Treated Individuals.

OBJECTIVE: To examine associations between plasma cystatin C and neurocognitive impairment (NCI) and its performance as a diagnostic marker before and during initial antiretroviral therapy (ART). METHODS: Multivariable logistic regression and generalized estimating equations examined associations with NCI, determined by neuropsychological measurements, in participants of a 48-week randomized clinical trial of initial ART. Receiver operator characteristic curves examined diagnostic models of NCI. RESULTS: Cystatin C was associated with NCI before ART [odds ratio (OR) 3.4 (95% CI: 1.2 to 9.4) for each 2-fold increase in baseline levels] and during 48 weeks of ART, in models that excluded baseline measurements [OR 3.0 (1.2 to 7.8) for each 2-fold increase in time-updated levels]. The strength of association increased with more severe impairment using HIV-associated neurocognitive disorder criteria [OR 2.2 (0.8 to 6.0) with asymptomatic NCI and OR 4.0 (1.5 to 11.0) with mild neurocognitive disorder or HIV-associated dementia vs. no impairment, for each 2-fold increase in time-updated levels] or by global development score [OR 2.6 (1.1 to 6.3) with mild impairment and OR 4.6 (1.1 to 18.9) with moderate or severe impairment vs. no impairment]. Cystatin C performed poorly as a diagnostic marker for NCI, however, with an area under the receiver operator characteristic curve of 0.58 at baseline and 0.54 at week 48. CONCLUSIONS: Higher plasma cystatin C levels were significantly associated with NCI, but these levels did not seem to be useful as a diagnostic marker for this condition.

Cervical cancer survival in a resource-limited setting-North Central Nigeria.

BACKGROUND: Organized cervical cancer screening services are presently lacking in Nigeria contributing to late presentation and diagnosis of invasive cervical cancer cases (ICCs) at advanced stages in most gynecologic units in Nigeria. We evaluated outcomes of ICCs diagnosed at Jos University Teaching Hospital (JUTH) to better understand factors associated with cervical cancer survival in similar resource limited settings. METHODS: We performed a retrospective cohort study with a prospective follow up data to estimate time from diagnosis to mortality among women diagnosed with ICCs at JUTH. Women who were diagnosed with ICCs between January 2011 and May 2013 were followed up after initial evaluation at JUTH and subsequent referral for specialized treatment in one of the national oncology treatment centers in Nigeria. The main outcome measured was all-cause mortality rate and overall survival (OS) after diagnosis of ICC. The follow up data were updated and observations were censored March 31, 2015. The overall death rate was estimated using the total number of death events and the cumulative follow-up time from diagnosis to death. We conducted Cox proportional hazard regression to assess factors associated with death. RESULTS: A total of 65 histologically confirmed ICCs were followed up. The median age of the cohort was 50 years with a median parity of 7. The HIV prevalence in the cohort was 8.2 % and the majority (72.3 %) were diagnosed at advanced stages (AD) of ICC. Simple total abdominal hysterectomy (TAH) was performed in 38.9 % of patients who were diagnosed at early stage disease (ED). After a cumulative follow up of 526.17 months, 35 deaths occurred with an overall death rate of 79.8 per 100 women-years. We also found a significantly higher hazard of death in women with AD (HR = 3.3) and baseline anemia (HR = 3.0). In the subgroup of women with ED, the OS was significantly higher for those who had TAH compared to those who did not (26.5 versus 11.6 months respectively). CONCLUSION: Advanced stage disease and baseline anemia were independently associated with higher death rate. Cervical cancer patients diagnosed at early stages by non-oncologic specialist in settings lacking the standard of care may benefit from improve survival with simple hysterectomy.

HIV Associated Chronic Obstructive Pulmonary Disease in Nigeria.

OBJECTIVE: To determine the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) among HIV-infected adults in Nigeria. DESIGN: Cross-sectional study. METHODS: HIV-infected adults aged ≥ 30 years with no acute ailments accessing care at the antiretroviral therapy clinic of Jos University Teaching Hospital were enrolled consecutively. Participants were interviewed to obtain pertinent demographic and clinical information, including exposure to risk factors for COPD. Post-bronchodilator spirometry was carried out. HIV related information was retrieved from the clinic medical records. COPD case-definition was based on the Global Initiative for Obstructive Lung Disease (GOLD) criteria using post-bronchodilator FEV1/FVC <0.7. COPD prevalence was also calculated using the lower limit of normal for FEV1/FVC criteria (LLN) from the European Respiratory Society normative equation. Factors associated with COPD were determined using logistic regression models. RESULTS: Study population comprised 356 HIV infected adults with mean age of 44.5 (standard deviation, 7.1) years and 59% were female. The mean time elapsed since HIV diagnosis was 7.0 (SD, 2.6) years and 97.5% of the respondents were on stable ART with virologic suppression present in 67.2%. Prevalence of COPD were 15.4% (95% confidence interval [CI] 11.7-19.2), 12.07% (95% CI 8.67-15.48), 22.19% (95% CI 18.16-26.83) using GOLD, ERS LLN and GLI LLN diagnostic criteria respectively. In multivariate analyses adjusting for gender, exposure to cigarette smoke or biomass, history of pulmonary tuberculosis, use of antiretroviral therapy, current CD4 T-cell count and HIV RNA, only age > 50 years was independently associated with COPD with OR 3.4; 95% CI 1.42-8.17 when compared to ages 30-40 years. CONCLUSION: HIV-associated COPD is common in our population of HIV patients.