HIV Therapy Research Articles

Impact of Antiretroviral Agents on Blood Cell Parameters

Human immunodeficiency virus infection continues to be a major public health challenge in under-developed regions due to poverty, war and illiteracy. In developed countries, where much success has been achieved in fighting the menace, access to improved therapy is largely responsible. Nevertheless, studies have linked HIV and antiretroviral therapy with increased risk of cytopenia of all major blood cell lines and associated morbidities such as anaemia and platelet-driven cardiovascular events. Some antiretroviral agents such as zidovudine are associated with bone marrow suppression and an increased risk of developing anaemia Stavudine, azidothymidine and lamivudine have been linked with macrocytic anaemia in patients taking them. Lamivudine in combination with zidovudine causes neutropenia, anaemia and thrombocytopenia. Nevirapine causes eosinophilia, granulopenia and increased enzyme activities. Abacavir sulphate has been linked with increased risk of platelet-driven cardiovascular complications. The advocacy for combined therapy has helped to curb the effects of these agents when taken individually. Prolonged use of highly active antiretroviral therapy has been shown to correct some of these cytopenias and their associated morbidities. In managing HIV-infected patients however regular monitoring of their blood cell parameters and CD4+ count is required to ascertain the efficacy of the regimen being used in treatment.

Analysis and simulation of a delayed HIV model with reaction–diffusion and sliding control

Selection of an appropriate therapy threshold to restrain the virus load is still challenging on structured treatment interruptions (STIs) for HIV. In this paper, we ponder that how the sliding control and multistability to regulate the treatment effect through comprehensive dynamics of a virus-immune model. Firstly, based on piecewise therapy, we propose a delayed reaction–diffusion virus-immune model under the homogeneous Neumann boundary condition. Secondly, the existence and stabilities of five kinds of equilibria as well as the direction and stability of spatial Hopf bifurcation at regular equilibrium are investigated. Thirdly, the sliding domain and the boundary node bifurcations are addressed by theoretical analysis. Finally, we appraise the effects of therapy threshold, sliding domain and multistability on HIV therapy by simulations, and further seek out the appropriate therapy threshold for infected patients with given physiological parameters and present the corresponding principles. Our explorations will provide evidence for HIV and other disease therapies.

Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study

BackgroundProlonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population.MethodsThis was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin.ResultsOf the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 μm/L ranging from 8.44 μm/L and 1,979.36 μm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 μm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 — 149.95, p < 0.05).ConclusionsThe majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.

Developments in Exploring Fungal Secondary Metabolites as Antiviral Compounds and Advances in HIV-1 Inhibitor Screening Assays.

The emergence of drug-resistant Human Immunodeficiency Virus-1 strains against anti-HIV therapies in the clinical pipeline, and the persistence of HIV in cellular reservoirs remains a significant concern. Therefore, there is a continuous need to discover and develop new, safer, and effective drugs targeting novel sites to combat HIV-1. The fungal species are gaining increasing attention as alternative sources of anti-HIV compounds or immunomodulators that can escape the current barriers to cure. Despite the potential of the fungal kingdom as a source for diverse chemistries that can yield novel HIV therapies, there are few comprehensive reports on the progress made thus far in the search for fungal species with the capacity to produce anti-HIV compounds. This review provides insights into the recent research developments on natural products produced by fungal species, particularly fungal endophytes exhibiting immunomodulatory or anti-HIV activities. In this study, we first explore currently existing therapies for various HIV-1 target sites. Then we assess the various activity assays developed for gauging antiviral activity production from microbial sources since they are crucial in the early screening phases for discovering novel anti-HIV compounds. Finally, we explore fungal secondary metabolites compounds that have been characterized at the structural level and demonstrate their potential as inhibitors of various HIV-1 target sites.

A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals

A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals

Independent Effects of HIV and Antiretroviral Therapy on the Oral Microbiome Identified by Multivariate Analyses.

The oral microbiome is an important predictor of health and disease. We recently reported significant yet modest effects of HIV under highly active antiretroviral therapy (ART) on the oral microbiome (bacterial and fungal) in a large cohort of HIV-positive (HIV+) and matched HIV-negative (HIV-) individuals. As it was unclear whether ART added to or masked further effects of HIV on the oral microbiome, the present study aimed to analyze the effects of HIV and ART independently, which also included HIV- subjects on preexposure prophylaxis (PrEP) therapy. Cross-sectional analyses of the effect of HIV devoid of ART (HIV+ ART- versus matched HIV- subjects) showed a significant effect on both the bacteriome and mycobiome (P < 0.024) after controlling for other clinical variables (permutational multivariate analysis of variance [PERMANOVA] of Bray-Curtis dissimilarity). Cross-sectional analyses evaluating the effects of ART (HIV+ ART+ versus HIV+ ART- subjects) revealed a significant effect on the mycobiome (P < 0.007) but not the bacteriome. In parallel longitudinal analyses, ART (before versus after the initiation of ART) had a significant effect on the bacteriome, but not the mycobiome, of HIV+ and HIV- PrEP subjects (P < 0.005 and P < 0.016, respectively). These analyses also revealed significant differences in the oral microbiome and several clinical variables between HIV- PrEP subjects (pre-PrEP) and the HIV-matched HIV- group (P < 0.001). At the species level, a small number of differences in both bacterial and fungal taxa were identified within the effects of HIV and/or ART. We conclude that the effects of HIV and ART on the oral microbiome are similar to those of the clinical variables but collectively are modest overall. IMPORTANCE The oral microbiome can be an important predictor of health and disease. For persons living with HIV (PLWH), HIV and highly active antiretroviral therapy (ART) may have a significant influence on their oral microbiome. We previously reported a significant effect of HIV with ART on both the bacteriome and mycobiome. It was unclear whether ART added to or masked further effects of HIV on the oral microbiome. Hence, it was important to evaluate the effects of HIV and ART independently. For this, multivariate cross-sectional and longitudinal oral microbiome analyses (bacteriome and mycobiome) were conducted within the cohort, including HIV+ ART+ subjects and HIV+ and HIV- (preexposure prophylaxis [PrEP]) subjects before and after the initiation of ART. While we report independent significant effects of HIV and ART on the oral microbiome, we conclude that their influence is similar to that of the clinical variables but collectively modest overall.

A Randomized Clinical Trial of Transgender Women Switching to B/F/TAF: The (mo)BETTA Trial.

Cardiometabolic disease in transgender women (TW) is affected by gender-affirming hormonal therapies (GAHTs), HIV, and antiretroviral therapy (ART). We evaluated the 48-week safety/tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs continued ART in TW on GAHT. TW on GAHT and suppressive ART were randomized 1:1 to switch to B/F/TAF (Arm A) or continue current ART (Arm B). Cardiometabolic biomarkers, sex hormones, bone mineral density (BMD) and lean/fat mass by DXA scan, and hepatic fat (controlled continuation parameter [CAP]) were measured. Wilcoxon rank-sum/signed-rank and χ2 tests compared continuous and categorical variables. TW (Arm A n = 12, Arm B n = 9) had a median age of 45 years. Ninety-five percent were non-White; 70% were on elvitegravir or dolutegravir, 57% TAF, 24% abacavir, and 19% TDF; 29% had hypertension, 5% diabetes, and 62% dyslipidemia. There were no adverse events. Arm A/B had 91%/89% undetectable HIV-1 RNA at week 48 (w48). Baseline (BL) osteopenia (Arm A/B 42%/25%) and osteoporosis (17%/13%) were common, without significant changes. BL lean/fat mass were similar. At w48, Arm A had stable lean mass but increased limb (3 lbs) and trunk (3 lbs) fat (within-arm P < .05); fat in Arm B remained stable. No changes occurred in lipid or glucose profiles. Arm B had a greater w48 decrease (-25 vs -3 dB/m; P = .03) in CAP. BL and w48 concentrations of all biomarkers were similar. In this cohort of TW, switch to B/F/TAF was safe and metabolically neutral, though greater fat gain occurred on B/F/TAF. Further study is needed to better understand cardiometabolic disease burden in TW with HIV.

Single-Administration Long-Acting Microarray Patch with Ultrahigh Loading Capacity and Multiple Releases of Thermally Stable Antibodies.

Current antibody (Ab) therapies require development of stable formulations and an optimal delivery system. Here, we present a new strategy to create a single-administration long-lasting Ab-delivery microarray (MA) patch, which can carry high doses of thermally stabilized Abs. The MA fabricated by an additive three-dimensional manufacturing technology can be fully embedded into the skin via a single application to deliver doses of Abs at multiple programmable time points, thus sustaining Ab concentrations in systemic circulation. We developed an MA formulation that stabilized and delivered human immunoglobulins (hIg) in a time-controlled manner while maintaining their structure and functionality. As an example, the b12 Ab─a broadly neutralizing Ab against HIV-1─maintained antiviral activity in vitro after MA manufacturing and heat exposure. Pharmacokinetic studies of MA patch-delivered hIg in rats successfully provided a proof of concept for concurrent and time-delayed Ab delivery. These MA patches codeliver different Abs, providing a tool for expanded protection against viral infections or combination HIV therapy and prevention.

Development of an Isothermal Point-of-care Genetic Rapid Test for the Detection of the HLA-B*57:01 Allele, a Predictor for Hypersensitivity Reaction Caused by Abacavir, for Stratifying Patients for Antiretroviral Abacavir HIV Therapy

Background: Abacavir is used in the treatment of HIV-infected patients. A hypersensitive reaction (HSR) occurs in about 5-8% of patients treated with Abacavir. The HLA-B*57:01 allele is a valuable predictor for HSR and its screening is mandatory prior to treatment with Abacavir. Objective: Current screening methods require considerable investments for equipment. In order to lower the required investments and enable physician practices to perform the screening in a point-of-care (PoC) setting, our objective was to develop a novel isothermal genetic rapid test that requires a minimal setup cost, does not require specific training and thus is suitable for a physician practice setting. Methods: We developed an isothermal recombinase polymerase amplification (RPA) for the specific amplification of the HLA-B*57:01 allele using allele-specific primers coupled to Biotin. Primers specific for human lactase gene, coupled to Digoxigenin, were used as an internal amplification control (IAC). Lateral flow dipstick provided rapid and accurate detection of HLA-B*57:01 allele and IAC via the respective antibodies sprayed on the strips surface. Results: The reference method identified the HLA-B*57:01 allele in the reference sample, in 2 out of 28 buccal swab samples and in 2 out of 13 blood samples. The initial isothermal RPA resulted in unspecific amplification of the HLA-B*57:01 allele. By further optimization steps the specific amplification of the allele and the detection on lateral flow dipstick was observed. The newly developed isothermal RPA was validated. Conclusion: The method developed fulfils the requirements for a genetically based PoC screening system for the HLA-B*57:01 variant, requiring a minimal investment for a heating block and a pipette.

Missed and Lost to Follow-up Cases in HIV Positive Patients and the Impact of Lockdown During COVID-19 Pandemic on Adherence to Anti-retroviral Therapy at ART Center, Jhansi, Uttar Pradesh

Background: Anti-retroviral therapy (ART) for HIV has changed a highly fatal disease to a chronic manageable condition. National technical guidelines by NACO say that adherence of &gt;95%(optimal) is required for optimal viral load suppression which is a challenge both for the patient and the health system. Objectives: This study was conducted to determine the reasons for missed and lost to follow-up (LFU) cases and to assess the impact of the COVID pandemic on ART adherence. Settings and Design: Cross-sectional study conducted at ART center, Jhansi. Methods and Material: 357 patients were administered a self-designed questionnaire after taking informed consent to enquire about the reasons for missing doses and LFU and whether they missed treatment during the lockdown. Statistical analysis used: the results were expressed in frequencies and percentages and appropriate statistical tests were applied. Results: 72% HIV patients had optimal adherence and 6.7% were on second-line treatment. Out of 357 patients, 56 had missed treatment and 10 were LFU. The main reasons for the missing were run out of pills, busy with other things and being away from home. The number of episodes of missed and LFU increased during the pandemic. The main problems faced were lack of transport (24), fear of catching the disease (7), no money to hire a vehicle (5). Conclusions: Constant monitoring and handholding of those with suboptimal adherence is required. Travel allowance to such patients and regular counseling will help to ensure adherence. Long-term solutions include vocational rehabilitation and awareness programs to reduce stigma and discrimination.

A potential anti-HIV-1 compound, Q308, inhibits HSV-2 infection and replication in vitro and in vivo

HSV-2 is a common human pathogen worldwide that causes genital herpes. Due to the lack of an effective HSV-2 vaccine in the foreseeable future, there is an urgent need to develop effective, safe and affordable anti-HSV-2 agents. Our previous studies confirmed that a small-molecule compound, Q308, effectively inhibits the reactivation of latent HIV and might be developed as an anti-HIV-1 agent. Patients infected with HSV-2 are generally more susceptible to HIV-1 infection than normal humans. In this study, we found that Q308 treatment had strong inhibitory activity against both HSV-2 and acyclovir-resistant HSV-2 strains in vitro and reduced the viral titers in tissue. And this treatment effectively ameliorated the cytokine storm and pathohistological changes caused by HSV-2 infection in HSV-2-infected mice. Unlike nucleoside analogs such as acyclovir, Q308 inhibited post-viral entry events by attenuating the synthesis of viral proteins. Furthermore, Q308 treatment blocked HSV-2-induced PI3K/AKT phosphorylation due to its inhibition on viral infection and replication. Overall, Q308 treatment exhibits potent anti-HSV-2 activity by inhibiting viral replication both in vitro and in vivo. Q308 is a promising lead compound for the development of new anti-HSV-2/HIV-1 therapies, particularly against acyclovir-resistant HSV-2 strains.

Transmission modeling to infer tuberculosis incidence prevalence and mortality in settings with generalized HIV epidemics

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential intervention impact. We therefore develop a novel age-structured TB transmission model incorporating evolving demographic, HIV and antiretroviral therapy effects, and calibrate to TB prevalence and notification data from 12 African countries. We use Bayesian methods to include uncertainty for all TB model parameters, and estimate age-specific annual risks of TB infection, finding up to 16.0%/year in adults, and the proportion of TB incidence from recent (re)infection, finding a mean across countries of 34%. Rapid reduction of the unacceptably high burden of TB in high HIV prevalence settings will require interventions addressing progression as well as transmission.

Developing CAR T and CAR NK cells for HIV-1 eradication

Since HIV-1 was first discovered in the early 1980s, this virus has killed nearly 400,000 people around the world. However, up to now, there is no known cure for HIV-1 infection, because the removal of the HIV-1 repository is unreachable. In recent years, scientists began to apply the chimeric antigen receptor (CAR), an immunotherapy that has made great progress in hematological malignancies treatment, to the remedy of people infected with HIV-1, hoping to "kill" the virus completely after "shock" treatment. This review discussed the latest research progress of different types of CAR T cells, including CD4-based, scFv-based, and bi-/tri-specific CAR T cells, in HIV-1 therapy, and their advantages and limitations in detail. Additionally, it also briefly reviewed the function of NK cells in fighting HIV-1 infection and summarized the research results of CAR NK cells in AIDS treatment.

Nonsuppressible viremia during HIV-1 therapy meets molecular virology.

HIV-1 replication can be suppressed with antiretroviral therapy (ART), but individuals who stop taking ART soon become viremic again. Some people experience extended times of detectable viremia despite optimal adherence to ART. In this issue of the JCI, White, Wu, and coauthors elucidate a source of nonsuppressible viremia (NSV) in treatment-adherent patients - clonally expanded T cells harboring HIV-1 proviruses with small deletions or mutations in the 5'-leader, the UTR that includes the major splice donor site of viral RNA. These mutations altered viral RNA-splicing efficiency and RNA dimerization and packaging, yet still allowed production of detectable levels of noninfectious virus particles. These particles lacked the HIV-1 Env surface protein required for cell entry and failed to form the mature capsid cone required for infectivity. These studies improve our understanding of NSV and the regulation of viral functions in the 5'-leader with implications for rationalized care in individuals with NSV.

Prevalence and factors associated with pediatric HIV therapy failure in a tertiary hospital in Asmara, Eritrea: A 15-year retrospective cohort study.

Treatment failure (TF) in HIV infected children is a major concern in resource-constrained settings in Sub-Saharan Africa (SSA). This study investigated the prevalence, incidence, and factors associated with first-line cART failure using the virologic (plasma viral load), immunologic and clinical criteria among HIV-infected children. A retrospective cohort study of children (<18 years of age on treatment for a period of > 6 months) enrolled in the pediatric HIV/AIDs treatment program at Orotta National Pediatric Referral Hospital from January 2005 to December 2020 was conducted. Data were summarized using percentages, medians (± interquartile range (IQR)), or mean ± standard deviation (SD). Where appropriate, Pearson Chi-Squire (χ2) tests or Fishers exacts test, Kaplan-Meier (KM) estimates, and unadjusted and adjusted Cox-proportional hazard regression models were employed. Out of 724 children with at least 24 weeks' follow-up 279 experienced therapy failure (TF) making prevalence of 38.5% (95% CI 35-42.2) over a median follow-up of 72 months (IQR, 49-112 months), with a crude incidence of failure of 6.5 events per 100- person-years (95% CI 5.8-7.3). In the adjusted Cox proportional hazards model, independent factors of TF were suboptimal adherence (Adjusted Hazard Ratio (aHR) = 2.9, 95% CI 2.2-3.9, p < 0.001), cART backbone other than Zidovudine and Lamivudine (aHR = 1.6, 95% CI 1.1-2.2, p = 0.01), severe immunosuppression (aHR = 1.5, 95% CI 1-2.4, p = 0.04), wasting or weight for height z-score < -2 (aHR = 1.5, 95% CI 1.1-2.1, p = 0.02), late cART initiation calendar years (aHR = 1.15, 95% CI 1.1-1.3, p < 0.001), and older age at cART initiation (aHR = 1.01, 95% CI 1-1.02, p < 0.001). Seven in one hundred children on first-line cART are likely to develop TF every year. To address this problem, access to viral load tests, adherence support, integration nutritional care into the clinic, and research on factors associated with suboptimal adherence should be prioritized.

Structure-directed expansion of biphenyl-pyridone derivatives as potent non-nucleoside reverse transcriptase inhibitors with significantly improved potency and safety

Following our previous work on human immunodeficiency virus-1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs), a series of novel biphenyl-pyridone derivatives were synthesized and evaluated for their anti-HIV-1 activity to expand their structure–activity relationship. Some of them exhibited low nanomolar activity toward wild-type HIV-1 and clinically relevant single/double mutant strains. The most active compound B1 was 231-fold more potent (EC50 = 17 nmol/L) than the lead compound 2 (EC50 = 3.93 µmol/L) against wild-type (WT) HIV-1. This compound was approximately 3.5-fold less cytotoxic (CC50 = 100.58 µmol/L) than compound 2 (CC50 = 28.24 µmol/L), presenting a higher selectivity index (SI) value of 5923. Compared with 2, the antiviral potency of B1 was significantly increased against five single mutant strains (L100I, K103N, E138K, Y181C and Y188L) and two double mutant strains (F227L+V106A and K103N+Y181C). Especially, K103N, Y181C and K103N+Y181C were more sensitive to B1 than both 2 and doravirine. Besides, the enzymatic inhibitory activity of B1 against wild-type HIV-1 reverse transcriptase was approximately 32-fold higher (IC50 = 100 nmol/L) than 2 (IC50 = 3.21 µmol/L). Molecular docking studies and dynamic simulations were conducted to explain their potent activity. Taken together, this research represents an important step toward the discovery of novel biphenyl-pyridone drug candidates for HIV therapy.

HIV therapy adherence and outcomes in Peruvian military personnel over a 30-year period

&lt;b&gt;Objectives: &lt;/b&gt;We aimed to describe the sociodemographic, clinical, and therapeutic characteristics of Peruvian military personnel diagnosed with HIV. Furthermore, we determined the frequency of highly active antiretroviral therapy (HAART) adherence, the complications and mortality.&lt;br /&gt; &lt;b&gt;Methods:&lt;/b&gt; We retrospectively reviewed the medical records of patients diagnosed with HIV, confirmed by Western blot at a single institution from 1989-2020. Descriptive analyses were performed for all the variables using mean and standard deviation (SD) in the case of quantitative variables, and frequency and percentage for qualitative variables.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;Of the 161 patients included, 95.7% were males and the mean age was 39.59 years (SD= 16.45 years). Most had college or higher education (67.7%) and were on active duty at diagnosis (77%). 35.4% had AIDS at diagnosis; 28.6% opportunistic infections; and 8.1% tuberculosis. The median follow-up was five years. 94.4% of the patients received HAART as the principal treatment; of these, 88.8% was adherent to treatment, and death was reported in 6.8%. There were no factors associated with adherence.&lt;br /&gt; &lt;b&gt;Conclusions: &lt;/b&gt;Although the sociodemographic characteristics of Peruvian military personnel are similar to those of other countries, our findings suggest that Peruvian military personnel present higher adherence to HAART compared to previous studies in other military populations from South American countries. Further studies are recommended to assess specific factors attributed to these successful outcomes in the military personnel that can be applied in other hospitals.

Fertility trends by HIV status in a health and demographic surveillance study in Magu District, Tanzania, 1994-2018.

Sub-Saharan Africa (SSA) has the highest fertility rates and highest HIV disease burden globally. However, it is not clear how the rapid expansion of anti-retroviral therapy (ART) for HIV has impacted the fertility gap between HIV-infected and uninfected women. We used data from a Health and Demographic Surveillance System (HDSS) in north-western Tanzania to explore trends in fertility rates and the relationship between HIV and fertility over the 25-year period. From 1994 to 2018, births and population denominators from the HDSS population were used to obtain age-specific fertility rates (ASFRs) and total fertility rates (TFRs). HIV status was extracted from eight rounds of epidemiologic serological surveillances (1994-2017). Fertility rates by HIV status and in different levels of ART availability were compared over time. Independent risk factors for fertility changes were examined using Cox proportional hazard models. There were 24,662 births from 36,814 women (15-49) who contributed a total of 145,452.5 Person-Years of follow-ups. The TFR declined from 6.5 births per woman in 1994-1998 to 4.3 births per woman in 2014-2018. The number of births per woman was 40% lower in women living with HIV than in HIV-uninfected women (4.4 vs. 6.7), although this difference narrowed over time. The fertility rate in HIV-uninfected women was 36% lower in 2013-2018 than in 1994-1998(age-adjusted HR = 0.641; 95% CI 0.613-0.673). In contrast, the fertility rate in women living with HIV was relatively unchanged over the same follow up period (age-adjusted HR = 1.099; 95% CI 0.870-1.387). There was a notable fertility decline among women in the study area from 1994 to 2018. Fertility remained lower in women living with HIV than in HIV-uninfected women, but the difference continued to narrow over time. These results highlight the need for more research into fertility changes, fertility desire and family planning use in Tanzanian rural communities.

Hypertensive disorders of pregnancy and HIV: analysis of a province-wide cohort during 2018 and 2019.

We evaluated the prevalence of de novo hypertensive disorders of pregnancy (dnHDP) in pregnant people with HIV (PPHIV) in the Western Cape Province, South Africa in 2018-2019 by HIV and antiretroviral therapy (ART) status. All people with a pregnancy outcome from 1 January 2018 to 31 December 2019 in the Western Cape Provincial Health Data Centre (WCPHDC) were included. The WCPHDC integrates data from multiple electronic platforms according to unique identifiers. dnHDP was classified by ICD-10 code or first-time prescription of antihypertensive drugs less than 140 days before delivery. Pregnant people with preexisting hypertension without superimposed preeclampsia/eclampsia were not considered to have dnHDP. Adjusted prevalence ratios (aPR) for dnHDP by HIV/ART status were calculated using Poisson regression with robust variance. Among 180 553 pregnant people studied, 13 677 (7.6%) had dnHDP and 33 978 (18.8%) were PPHIV. Among PPHIV, 11.3% ( N = 3827) had no evidence of ART, 59.7% ( N = 20 283) initiated ART preconception and 29.0% ( N = 9868) had ART initiated during pregnancy. Compared to those without HIV (7.7%), dnHDP prevalence was lower in PPHIV with preconception [6.9%; aPR 0.78; 95% confidence interval (CI) 0.74-0.83] or pregnancy-initiated ART (7.0%; aPR 0.83; 95% CI 0.75-0.92) and higher in PPHIV without ART (9.8%; aPR 1.17; 95% CI 1.06-1.29) adjusted for maternal age, multiparity, multigestation pregnancy and preexisting hypertension. ART duration by delivery of at least 100 weeks versus pregnancy-initiated ART of 20-<40 weeks was protective (aPR 0.88; 95% CI 0.78-0.98). In the context of universal ART, these findings are reassuring for most PPHIV. ART was not associated with increased dnHDP prevalence and longer ART duration was protective.

Health Equity in Sickle Cell Research and Access to Therapy

Health Equity in Sickle Cell Research and Access to Therapy