Provision Of Antiretroviral Therapy Research Articles

HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre longitudinal study (DTG RESIST).

HIV drug resistance poses a challenge to the United Nation's goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was endorsed by the World Health Organization in 2019 for first-, second-, and third-line antiretroviral therapy (ART). This multiplicity of roles of dolutegravir in ART may facilitate the emergence of dolutegravir resistance. DTG RESIST is a multicentre longitudinal study of adults and adolescents living with HIV in sub-Saharan Africa, Asia, and South and Central America who experienced virologic failure on dolutegravir-based ART. At the time of virologic failure whole blood will be collected and processed to prepare plasma or dried blood spots. Laboratories in Durban, Mexico City and Bangkok will perform genotyping. Analyses will focus on (i) individuals who experienced virologic failure on dolutegravir, and (ii) on those who started or switched to such a regimen and were at risk of virologic failure. For population (i), the outcome will be any InSTI drug resistance mutations, and for population (ii) virologic failure defined as a viral load >1000 copies/mL. Phenotypic testing will focus on non-B subtype viruses with major InSTI resistance mutations. Bayesian evolutionary models will explore and predict treatment failure genotypes. The study will have intermediate statistical power to detect differences in resistance mutation prevalence between major HIV-1 subtypes; ample power to identify risk factors for virologic failure and limited power for analysing factors associated with individual InSTI drug resistance mutations. The research protocol was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, South Africa, and the Ethics Committee of the Canton of Bern, Switzerland. All sites participate in IeDEA and have obtained ethics approval from their local ethics committee to conduct the additional data collection. NCT06285110. - DTG RESIST is a large international study to prospectively examine emergent dolutegravir resistance in diverse settings characterised by different HIV-1 subtypes, provision of ART, and guidelines on resistance testing. - Embedded within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST will benefit from harmonized clinical data across participating sites and expertise in clinical, epidemiological, biological, and computational fields. - Procedures for sequencing and assembling genomes from different HIV-1 strains will be developed at the heart of the HIV epidemic, by the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), in Durban, South Africa. Phenotypic testing, Genome Wide Association Study (GWAS) methods and Bayesian evolutionary models will explore and predict treatment failure genotypes. - A significant limitation is the absence of genotypic resistance data from participants before they started dolutegravir treatment, as collecting and bio-banking pre-treatment samples was not feasible at most IeDEA sites. Consistent and harmonized data on adherence to treatment are also lacking. - The distribution of HIV-1 subtypes across different sites is uncertain, which may limit the statistical power of the study in analysing patterns and risk factors for dolutegravir resistance. The results from GWAS and Bayesian modelling analyses will be preliminary and hypothesis-generating.

Predictors of Mortality Among Children and Adolescents Living With HIV on Antiretroviral Therapy in Western Kenya.

Antiretroviral therapy (ART) has decreased HIV-attributable deaths; however, children and adolescents continue to have high HIV-associated mortality. We determined the predictors of death among children and young adolescents living with HIV (CALWH) who died while in care in Western Kenya. This retrospective case-control study used electronically abstracted data of 6234 CALWH who received care in Academic Model Providing Access to Healthcare HIV clinics in Western Kenya between January 2002 and November 2022. The cases comprised CALWH who were reported dead by November 2022, while the controls constituted of matched CALWH who were alive and in care. Independent predictors of mortality were determined using univariable and multivariable Cox proportional hazard regression models. Kaplan-Meier analysis ascertained survival. Of the 6234 participants enrolled, slightly more than half were male (51.7%). The mean (SD) age at the start of ART was significantly lower in cases than in controls at 6.01 (4.37) and 6.62 (4.11) ( P < 0.001), respectively. An age of 11 years or older at start of ART (adjusted Hazard Ratio [aHR]: 8.36 [3.60-19.40]), both parents being alive (aHR: 3.06 [1.67-5.60]), underweight (aHR: 1.82 [1.14-2.92]), and World Health Organization stages 3 (aHR: 2.63 [1.12-6.18]) and 4 (aHR: 2.20 [0.94-5.18]) increased mortality; while school attendance (aHR: 0.12 [0.06-0.21]), high CD4 + counts >350 cells/mm 3 (aHR: 0.79 [0.48-1.29]), and low first viral load <1000 copies/mL (aHR: 0.24 [0.14-0.40]) were protective. Independent predictors of mortality were age 11 years or older at the start of ART, orphan status, underweight, and advanced HIV disease. Beyond the provision of universal ART, care accorded to CALWH necessitates optimization through tackling individual predictors of mortality.

Future HIV epidemic trajectories in South Africa and projected long-term consequences of reductions in general population HIV testing: a mathematical modelling study

After successful intensive interventions to rapidly increase HIV awareness, coverage of antiretroviral therapy (ART), and viral suppression, HIV programmes in eastern and southern Africa are considering scaling back of some interventions, such as widespread general population HIV testing. We aimed to model whether scaling back of general population HIV testing in South Africa could result in a resurgence of the HIV epidemic or substantial slowing of declines in HIV incidence, resulting in increased long-term ART. In this modelling study, we used the Thembisa 4.5 model (a deterministic compartmental model of HIV transmission in South Africa) to project the South African HIV epidemic to 2100 assuming the continuation of 2022 epidemiological conditions and HIV programme implementation. We assessed how implementing reductions in general population HIV testing services in 2025 (while maintaining antenatal, symptom-based, and risk-based testing modalities and other HIV prevention services at 2022 levels) would affect HIV incidence and prevalence among people aged 15-49 years, the year in which incidence would reach one per 1000 people aged 15-49 years (the threshold for virtual elimination of HIV), and associated costs, as well as numbers of additional new HIV infections and AIDS-related deaths. We also modelled the effects of delaying reductions in general population testing services by 5-year increments. Additionally, we modelled the potential effects of reductions in general population testing services in combination with increases or decreases in ART interruption rates (ie, the annual rate at which people who are on ART discontinue ART) and condom usage in 2025-35. If general population HIV testing services and the HIV risk environment of 2022 were maintained, we projected that HIV incidence would steadily decline from 4·95 (95% CI 4·40-5·34) per 1000 population in 2025 to 0·14 (0·05-0·31) per 1000 in 2100, and that the so-called virtual elimination threshold of less than one new infection per 1000 population per year would be reached in 2055 (95% CI 2051-2060). Scaling back of general population HIV testing services by 25%, 50%, or 75% in 2025 delayed time to reaching the virtual elimination threshold by 5, 13, or 35 years, respectively, whereas complete cessation of general population testing would result in the threshold not being attained by 2100. Although the incidence of HIV continued to fall when general HIV testing services were reduced, our modelling suggested that, with reductions of between 25% and 100%, between 396 000 (95% CI 299 000-474 000) and 2·50 million (1·97 million-2·98 million) additional HIV infections and between 115 000 (94 000-135 000) and 795 000 (670 000-926 000) additional AIDS-related deaths would occur between 2025 and 2075, depending on the extent of reduction in testing. Delaying reductions in general population HIV testing services for 5-25 years mitigated some of these effects. HIV testing accounted for only 5% of total programmatic costs at baseline; reducing testing moderately reduced short-term total annual costs, but increased annual costs after 25 years. Increases in ART interruption and reductions in condom usage were projected to slow the decline in incidence and increase the coverage of general HIV testing services required to control transmission but did not cause rapid resurgence in HIV infections. Our modelling suggests that scaling back of general population HIV testing would not result in a resurgence of HIV infections, but would delay attainment of incidence-reduction targets and result in long-term increases in HIV infections, AIDS-related deaths, and costs (via increased need for ART provision). HIV programmes need to balance short-term potential resource savings with long-term epidemic control objectives. Bill & Melinda Gates Foundation.

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viraemia during Universal Test and Treat scale-up in Uganda: a population-based study.

Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up. In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n= 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR= 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%). Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

The Vital Role of Public Health Nurses in Perinatal HIV Prevention and Elimination.

Perinatal HIV transmission remains a significant public health challenge, with an estimated 160,000 children newly infected with HIV each year. Public health nurses play a critical role in the prevention and elimination of perinatal HIV transmission through targeted interventions such as identification of pregnant women with HIV, referral and linkage to care, provision of antiretroviral therapy, and follow-up and retention in care for both mothers and infants. However, significant barriers to successful implementation exist, including stigma and discrimination, limited access to healthcare services, socioeconomic factors, and limited resources. Addressing these barriers will require a multifaceted approach that includes policy changes, community engagement, and targeted support and resources for affected families. In this review article, we provide an overview of the epidemiology of perinatal HIV transmission, current strategies for prevention and elimination, and the vital role of public health nurses in these efforts. We will also discuss the barriers to the successful implementation of public health nurse interventions and the future directions for research and practice in this field. Ultimately, the goal of perinatal HIV prevention and elimination can only be achieved through a sustained and collaborative effort across multiple sectors and stakeholders, with public health nurses playing a crucial role in this effort.

Provision of HIV services to psychiatric inpatients in Botswana: Challenges and recommendations.

The high prevalence of HIV among psychiatric inpatients is well-documented, yet little is known about the provision of HIV services for these patients. This qualitative study aimed to explore and understand healthcare providers' challenges with providing HIV services to psychiatric inpatients. This study was conducted at the national psychiatric referral hospital in Botswana. The authors conducted in-depth interviews with 25 healthcare providers serving HIV-positive psychiatric inpatients. Data analysis was performed using a thematic analysis approach. Healthcare providers reported challenges with transporting patients to access off-site HIV services, longer waiting periods for antiretroviral therapy (ART) initiation, patient confidentiality, fragmented services for treatment of comorbidities, and a lack of patient data integration between the national psychiatric referral hospital and other facilities such as the Infectious Diseases Care Clinic (IDCC) at the nearby district hospital. Providers' recommendations for addressing these challenges included the establishment of an IDCC at the national psychiatric referral hospital, connecting the psychiatric facility to the patient data management system to ensure integration of patient data, and provision of HIV-related in-service training to nurses. Psychiatric healthcare providers advocated for on-site integration of care for psychiatric illness and HIV among inpatients to address the challenges of ART provision. The findings suggest the need to improve the provision of HIV services in the psychiatric hospitals in order to ensure better outcomes for this often-overlooked population. These findings are useful in improving clinical practice for HIV in psychiatric settings.

The Efficacy of the Prevention of Mother-to-Child Transmission (PMTCT) Program in Mitigating Pediatric HIV/AIDS Incidence in the Mansa District, Zambia

This qualitative study was set out to intricately explore the landscape of the Prevention of Mother-to-Child Transmission (PMTCT) program in the Mansa district in order to shed light on its multifaceted nature. Key informants, pivotal to the program, offered invaluable insights into its fundamental components, recent progress, encountered challenges, and proposed improvements. The study emphasized the paramount importance of early detection and timely intervention in preventing HIV transmission from mother to child. The study highlighted key areas of focus within the PMTCT program, as elucidated by informants, emphasizing the central role of antenatal care, HIV testing and counseling, provision of antiretroviral therapy (ART), and vigilant postnatal follow-up. Together, these elements constituted a comprehensive strategy for safeguarding maternal and child well-being, with a strong emphasis on early identification and effective intervention. Recent developments in the program portrayed an evolving landscape, including enhancements such as improved access to rapid testing, the integration of maternal and child health services, expanded community outreach efforts, and initiatives aimed at enhancing community awareness. These innovations underscored the program’s adaptability and unwavering commitment to extending its reach. However, the challenges that impeded the reduction of mother-to-child HIV transmission were deeply rooted and multifaceted, encompassing issues such as stigma, inadequacies in healthcare infrastructure, medication adherence challenges, geographic barriers, personnel shortages, and logistical complexities. In response to these challenges, key informants put forth practical recommendations to strengthen the PMTCT program. These recommendations included broader community awareness and education efforts, the fortification of peer support networks, increased allocation of resources for transportation, and continuous training and sensitization programs for healthcare providers. These measures were deemed vital for enhancing program effectiveness and improving the health outcomes of mothers and infants in the Mansa district.

Incidence and epidemiology of conjunctival squamous cell carcinoma in relation to the HIV epidemic in South Africa: a 25-year analysis of the National Cancer Registry (1994–2018)

AimsTo describe the incidence and epidemiology of conjunctival squamous cell carcinoma (CSCC) in South Africa over a 25-year period (1994–2018), with particular reference to the HIV epidemic.MethodsIncident cases of histologically...

Surgical implications of HIV infection

According to the joint United Nations Programme on HIV/AIDS (UNAIDS), 37.7 million adults and children worldwide were estimated to be living with HIV or acquired immune deficiency syndrome (AIDS) at the end of 2020 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. Most reside in low- and middle-income countries, with approximately 67% in sub-Saharan Africa (SSA). At the end of 2020, the total number of children less than 15years of age living with HIV infection was 2.6 million, of whom 2.3 million (88%) were living in SSA. Aggressive interventions have reduced the annual number of incident (new) HIV infections among children to around 150,000 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. However, paediatric HIV infection remains a pandemic affecting children predominantly in SSA but is also seen in Asia and sporadically elsewhere particularly in areas of civil strife such as is currently the case in Ukraine [War in Ukraine. (2022). https://www.unaids.org/en/War-Ukraine-special . Accessed Apr 2022]. New HIV infections among children declined by more than half (54%) from 2010 to 2020, due mainly to the increased provision of antiretroviral therapy to pregnant and breastfeeding women living with HIV [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. These programmes include early identification of HIV infection in pregnant or breastfeeding women through routine HIV testing, provision of antiretroviral therapy (ART) to all HIV-infected women who are pregnant or breastfeeding, provision of antiretroviral prophylaxis to their newborn infants during the first 6-12weeks of life, delivery by elective Caesarean section when indicated, promotion of exclusive breastfeeding, early infancy screening for HIV infection, and initiation of ART in infants with HIV infection. HIV-infected children may require surgery either as an emergency to deal with a life-threatening incidental condition unrelated to HIV infection or for a complication of the disease such as tuberculosis or an aggressive soft tissue infection like necrotising fasciitis. Non-emergency surgical procedures may be required to assist in the diagnosis of an HIV-related condition or to correct a routine surgical problem electively. Surgical conditions associated with HIV infection are described under categories of soft tissue or organ-specific infections requiring drainage or debridement; gastrointestinal tract disease and complications; infections in the perineal area; malignancies and HIV-associated vasculitis. Although surgical outcomes are less favourable in HIV-infected children, pre-operative treatment of coinfections, administration of cotrimoxazole prophylaxis, nutritional support and antiretroviral therapy, together with peri-operative antibiotic prophylaxis have resulted in excellent short-term outcomes [World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach, June 201 http://www.apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf?ua=1 ; World Health Organization Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, September 2015. http://www.apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf?ua=1;Eley et al. in BMC Infect Dis 2:3, 2002;Karpelowsky et al. in Pediatr Surg Int 28:1007-1014, 2012;].

Vertical HIV transmission within 18 months post partum among women on lifelong antiretroviral therapy for HIV in Dar es Salaam, Tanzania: a prospective cohort study

The UNAIDS estimate of vertical HIV transmission in Tanzania is high (11%), despite 84% uptake of antiretroviral therapy (ART) among pregnant women with HIV. We aimed to evaluate vertical transmission and its determinants by 18 months post partum among women on lifelong ART in routine health-care settings in Tanzania. We conducted a prospective cohort study in 226 health facitilies across Dar-es-Salaam, Tanzania. Eligible participants were pregnant women of any age with HIV, and later their infants, who enrolled in routine health-care services for the prevention of vertical transmission. We prospectively followed up mother-infant pairs at routine monthly visits until 18 months post partum and extracted data from the care and treatment clinic (CTC2) database, a national electronic database that stores patient-level HIV care and treatment clinic data. The primary outcome was time from birth to HIV diagnosis, defined as a positive infant HIV DNA PCR or antibody test from age 18 months. We used the Kaplan-Meier method to estimate cumulative risk of vertical transmission by 18 months post partum and Cox proportional hazards regression with shared frailties to account for potential clustering in health facilities to evaluate predictors of transmission. Between Jan 1, 2015, and Dec 31, 2017, 22 930 pregnant women with HIV (median age 30 years, IQR 25-34) enrolled on a care programme. After excluding 9140 (39·9%) women and 539 (2·4%) infants with missing outcome data, 13 251 (59·0%) mother-infant pairs were analysed, of whom 6072 (45·8%) women were already on ART before pregnancy. By 18 months post partum, 159 (1·2%) of 13 251 infants were diagnosed with HIV, equivalent to a risk of vertical transmission of 1·4% (95% CI 1·2-1·6). In the complete case analysis, the rates of vertical transmission were higher among women who enrolled in the third trimester of pregnancy than among those who enrolled in the first trimester (adjusted hazard ratio 3·01, 95% CI 1·59-5·70; p=0·0003), among women with advanced HIV disease than among those with early-stage disease (1·89, 1·22-2·93; p=0·0046), and among women who were on a second-line ART regimen than among those on a first-line regimen (3·58, 1·08-11·82; p=0·037). By contrast, the rate of vertical transmission was lower among women who were already on ART at enrolment than among those starting ART at enrolment (0·39, 0·25-0·60; p<0·0001) as well as among women in high-volume clinics than among those in low-volume clinics (0·46 (0·24-0·90; p<0·0097). Provision of ART for life (WHO's option B+ recommendation) has reduced the risk of vertical transmission to less than 2% among pregnant women with HIV in routine care settings in urban Tanzania. There is still a need to improve timely HIV diagnosis and ART uptake, and to optimise follow-up for the prevention of vertical transmission and the uptake of infant HIV testing. Swedish International Development Cooperation Agency.

Impact of COVID-19 on HIV services and anticipated benefits of vaccination in restoring HIV services in Ethiopia: A qualitative assessment.

HIV services were inevitably disrupted and affected due to COVID-19. There are many challenges in implementing appropriate HIV services, particularly in the provision of health care and the link between people living with HIV/AIDS and retention in care. The study investigated the impact of COVID-19 on HIV services and the anticipated benefit of the COVID-19 vaccination on HIV service restoration in North Shewa, Oromia, Ethiopia. A qualitative descriptive study approach was used to explore how healthcare delivery evolved during the outbreak of COVID-19 in Ethiopia. Sixteen antiretroviral therapy (ART) clinics were selected from 13 districts and one administrative town in Ethiopia. From them, 32 ART providers were purposively selected based on their experience in ART provision. Data were collected from June to July 2021 using in-depth interviews. A thematic analysis approach was used to analyze the data, based on themes and subthemes emerging from the data. ATLAS.ti software was used for coding. Healthcare for people living with HIV was interrupted due to the COVID-19 pandemic. Medical appointments, HIV testing and counseling services, opportunistic infection treatment, medicine supply, and routine viral load and CD4 T-cell count tests were interrupted. Due to a shortage of healthcare staff, outreach testing services and home index testing were discontinued and HIV testing was limited only to hospitals and health centers. This has substantially affected accessibility to HIV testing and reduced the quality of HIV service delivery. Telehealth and less frequent visits to health facilities were used as alternative ways of delivering HIV services. The COVID-19 vaccination campaign is expected to restore healthcare services. Vaccination may also increase the confidence of healthcare providers by changing their attitudes toward COVID-19. The COVID-19 pandemic has substantially impacted HIV services and reduced the quality of HIV care in Ethiopia. Health facilities could not provide routine HIV services as they prioritize the fight against COVID-19, leading to an increase in service discontinuation and poor adherence.

Evaluating the Impact of the COVID-19 Pandemic on Accessing HIV Services in South Africa: A Systematic Review.

Progress has been made towards controlling the Human Immunodeficiency Virus (HIV) epidemic in South Africa. However, the emergence of coronavirus disease 2019 (COVID-19) has disrupted access to health care. This systematic review aims to evaluate the impact of the pandemic on accessing HIV services at a primary health care (PHC) level in South Africa. HIV services that have been significantly impacted are highlighted, and recommendations for future public health emergencies are made. Three databases were searched in January 2022. The studies included were those that reported on HIV services at a PHC level in South Africa. From the searches, 203 papers were identified, of which 34 full texts were screened. Eleven studies met the inclusion criteria and were included in this review. Overall, decreases in HIV testing, positive HIV tests, and initiation of antiretroviral therapy (ART) were reported. Resilience of ART provision was reported, meaning that adherence to treatment was sustained throughout the pandemic. The findings showed that HIV services at private PHC facilities were unaffected, however, an overall decrease in HIV services at public PHC facilities was reported, excluding antenatal care which showed resilience.

Pregnancy rates and outcomes in a longitudinal HIV cohort in the context of evolving antiretroviral treatment provision in South Africa

BackgroundIn South Africa, women continue to face a high burden of Human Immunodeficiency Virus (HIV) infection and the possible complications thereof during pregnancy. We assessed pregnancy incidence rates and outcomes in a longitudinal HIV cohort study over a 15-year period.MethodsWe evaluated pregnancies among women ≥ 18 years between 2004 and 2019 in the CAPRISA 002 study. We analysed pregnancy rates following HIV acquisition, CD4 counts and HIV viral load dynamics and pregnancy outcomes. We used linear regression to assess if the mean CD4 and log10 viral load close to delivery increases or decreases linearly across three different timepoints.ResultsIn total 245 women enrolled into the HIV negative study phase, 225 into the HIV infection phase and 232 in the antiretroviral therapy (ART) phase. Median follow-up time was 2.0 years [Interquartile Range (IQR) 0.8–2.0] during the HIV negative phase, 2.6 years; (IQR) 1.2–4.8] during HIV infection and 3.7 years (IQR 1.8–5.0) on ART, with maximum follow-up time of 2, 10 and 6 years respectively. Overall, 169 pregnancies occurred in 140 women, of which 16 pregnancies were observed during acute or early HIV infection [Incidence Rate (IR) 8.0 per 100 women-years; 95% confidence interval (CI): 4.6—12.9], 48 during established infection [IR 9.3; (CI 6.8–12.3)] and 68 on ART [IR 8.9; (CI: 7.0 – 11.4)]. Birth outcomes from 155/169 (91.7%) pregnancies were 118 (76.1%) full term live births, 17 (10.9%) premature live births, 9 (5.8%) therapeutic/elective miscarriages, 8 (5.1%) spontaneous miscarriages and 3 (1.9%) spontaneous foetal deaths or stillbirths. Six mother-to-child transmission events occurred, with four documented prior to 2008. Over time, mean CD4 count in pregnant women increased from 395 cells/µL (2004—2009) to 543 cells/µL (2010–2014) and to 696 cells/µL (2015–2019), p < 0.001. Conversely, the viral load declined from 4.2 log10 copies/ml to 2.5 log10 copies/ml and to 1.2 log10 copies/ml (p < 0.001) for the corresponding periods.ConclusionsPregnancy rates following HIV acquisition were high, emphasising a need for timeous ART provision and contraception counselling in women recently diagnosed with HIV. CD4 count and HIV viral load trajectories reflect improvements in treatment guidance for pregnant women over time.

The impact of HIV and tuberculosis interventions on South African adult tuberculosis trends, 1990-2019: a mathematical modeling analysis

ObjectivesTo quantify the South African adult tuberculosis (TB) incidence and mortality attributable to HIV between 1990 and 2019 and to estimate the reduction in TB incidence due to directly observed therapy, antiretroviral therapy (ART), isoniazid preventive therapy, increased TB screening, and Xpert MTB/RIF. MethodsWe developed a dynamic TB transmission model for South Africa. A Bayesian approach was used to calibrate the model to South African-specific data sources. Counterfactual scenarios were simulated to estimate TB incidence and mortality attributable to HIV and the impact of interventions on TB incidence. ResultsBetween 1990 and 2019, 8.8 million (95% confidence interval [CI] 8.3-9.3 million) individuals developed TB, and 2.1 million (95% CI 2.0-2.2 million) died from TB. A total of 55% and 69% of TB cases and mortality were due to HIV, respectively. Overall, TB screening and ART substantially reduced TB incidence by 28.2% (95% CI 26.4-29.8%) and 20.0% (95% CI 19.2-20.7%), respectively, in 2019; other interventions had minor impacts. ConclusionHIV has dramatically increased TB incidence and mortality in South Africa. The provision of ART and intensification of TB screening explained most recent declines in TB incidence.

Brief Report: Impact of COVID-19 on Cabotegravir Plus Rilpivirine Long-Acting Dosing Across 6 Ongoing Global Phase IIb and III Clinical Trials.

Cabotegravir + rilpivirine long-acting (LA) is a novel antiretroviral therapy (ART) administered intramuscularly monthly or every 2 months by a health care provider. The COVID-19 pandemic presents a potential challenge to patients' ability to attend scheduled clinic visits for dosing administration. This analysis evaluated implementation fidelity across 6 phase IIb/III/IIIb cabotegravir + rilpivirine LA clinical trials in 16 countries during the COVID-19 pandemic. COVID-19-impacted visits were defined as modified dosing visits for which oral therapy was provided to participants unable to attend the clinic or injection visits that were rescheduled. Data from December 1, 2019, to March 1, 2021, were aggregated and analyzed using descriptive statistics. Of 2127 participants in cabotegravir + rilpivirine LA trials, 1997 (94%) had LA dosing visits proceed as planned during the COVID-19 pandemic. Of 130 (6%) participants with injection visits affected by COVID-19, most were from North America (57%) and Europe (26%). Most participants with COVID-19-impacted visits used oral therapy with cabotegravir + rilpivirine (75%) or alternative oral standard-of-care ART (21%) to maintain continuous ART. The most common reasons for missed visits were clinic closure/staffing constraints (48%) and COVID-19-related travel restrictions (23%). Most (98%) participants who used oral ART maintained virologic suppression; 2 participants had viral load between 50 and 100 copies/mL. During the COVID-19 pandemic, most trial participants maintained their LA dosing schedules. Flexibility of the LA dosing regimen, with the ability to switch to oral therapy, facilitated continuous ART provision and implementation fidelity.

Explorative–descriptive study on the effects of COVID-19 on access to antiretroviral therapy services: the case of a teaching hospital in Ghana

ObjectiveTo explore how the COVID-19 pandemic affected access to antiretroviral therapy (ART) services from the perspective of the persons living with HIV (PLWH).DesignThe study adopted an exploratory-descriptive qualitative design that...

Integrated healthcare services for HIV, diabetes mellitus and hypertension in selected health facilities in Kampala and Wakiso districts, Uganda: A qualitative methods study.

Health policies in Africa are shifting towards integrated care services for chronic conditions, but in parts of Africa robust evidence on effectiveness is limited. We assessed the integration of vertical health services for HIV, diabetes and hypertension provided in a feasibility study within five health facilities in Uganda. From November 2018 to January 2020, we conducted a series of three in-depth interviews with 31, 29 and 24 service users attending the integrated clinics within Kampala and Wakiso districts. Ten healthcare workers were interviewed twice during the same period. Interviews were conducted in Luganda, translated into English, and analysed thematically using the concepts of availability, affordability and acceptability. All participants reported shortages of diabetes and hypertension drugs and diagnostic equipment prior to the establishment of the integrated clinics. These shortages were mostly addressed in the integrated clinics through a drugs buffer. Integration did not affect the already good provision of anti-retroviral therapy. The cost of transport reduced because of fewer clinic visits after integration. Healthcare workers reported that the main cause of non-adherence among users with diabetes and hypertension was poverty. Participants with diabetes and hypertension reported they could not afford private clinical investigations or purchase drugs prior to the establishment of the integrated clinics. The strengthening of drug supply for non-communicable conditions in the integrated clinics was welcomed. Most participants observed that the integrated clinic reduced feelings of stigma for those living with HIV. Sharing the clinic afforded privacy about an individual's condition, and users were comfortable with the waiting room sitting arrangement. We found that integrating non-communicable disease and HIV care had benefits for all users. Integrated care could be an effective model of care if service users have access to a reliable supply of basic medicines for both HIV and non-communicable disease conditions.

The Prevention of Mother-to-Child HIV/AIDS Transmission at Public Health Centers: A Phenomenology Study

Objective: Mothers with HIV are likely to transmit the virus to their babies during pregnancy, delivery, or through breastfeeding. According to studies, the risk of mother-to-child HIV transmission among mothers that do not receive any form of treatment during pregnancy is approximately 15-45%. In Indonesia, the lack of a prevention program for HIV led to the provision of antiretroviral therapy (ART) for the prevention of mother-to-child transmission (PMTCT). The policies, financial facilities, the healthcare system, and human resources, including health workers, are factors that influence the PMTCT. This research discusses the perceptions of several doctors and midwives regarding the prevention of mother-to-child transmission at public health centers. Furthermore, information regarding policies and implementation of the PMTCT program at public health centers in Yogyakarta was qualitatively collected through semi-structured interviews. Methods: This research involved 6 participants, comprising of 3 heads of public health centers and 3 midwives as the HIV/AIDS program managers. A total of 5 themes were selected for the interview, namely policies of mandatory HIV testing for pregnant mothers, inadequate knowledge of the virus, need for PMTCT training, infrastructure and facilities, and HIV retesting. Results: Pregnant mothers are at potential risk of exposing health workers to HIV. They are also prone to contracting the virus due to poor educational background and less exposure to health information. Therefore, midwives need Prongs 3 and 4 to avoid contracting the virus while assisting pregnant mothers. Presently, there is a shortage of health promotion media for PMTCT, which include both electronic and print educational media. Therefore, the implementation of HIV testing in Indonesia is mandatory for pregnant mothers at their first antenatal care (ANC). However, despite the importance of conducting this test before labor, there is no regulation to ensure its implementation. Conclusion: The success of HIV mitigation is closely associated with the participation of academicians, policymakers, and community networks in providing collaborative planning strategies for the reduction of its spread, and evaluation of the mitigation result.

‘You just prefer to die early!’: how socioecological context impedes treatment for people living with HIV in Iran

IntroductionDespite the low prevalence of HIV and broad provision of antiretroviral therapy, the Middle East and North Africa (MENA) remains the only region where new HIV infections and AIDS-related deaths...

RETRACTED: A Markov model examining intervention effects on the HIV prevalence/ incidence amongst the overall population

Human Immunodeficiency Virus (HIV) remains a high burden in Africa. Several targeted prevention strategies are prevalent including the promotion of condom use, provision of anti-retroviral therapy (ART) and pre-exposure prophylaxis (PrEP). Optimal allocation of limited resources requires understanding how the HIV epidemic will be affected by these strategies. We develop a Markov model, considering four sub-populations: female sex workers (FSWs), general population (GP), sex clients (SCs), and men who have sex with men (MSM), which estimates the effects of these strategies on the HIV prevalence/incidence in Rwanda from 2017 to 2027. Using Rwanda's demographic, sexual risk behavior, and HIV-associated morbidity/mortality data, it was determined that by 2027, a 30% improvement in consistent condom use amongst female sex workers would reduce the HIV prevalence amongst female sex workers, sex clients, and the general population by 7.86%, 5.97%, and 0.17%, respectively. Secondly, while making improvements on the recurrent HIV testing as well as ART coverage only mildly reduces the prevalence/incidence amongst female sex workers, and sex clients, reducing the two would result in an increase in the HIV prevalence/incidence amongst FSWs and SCs. Lastly, our analysis shows that introduction of PrEP to female sex workers in 2019 is expected to reduce the HIV incidence amongst FSWs by 1.28% over the next decade. We further analyze scaling-up PrEP beyond the highest-risk population, i.e., FSWs, and weigh population-level impact with cost-effectiveness to make an informed priority-setting amongst women in the general population. We modeled the HIV risk to women, and computed the impact, cost, and cost-effectiveness of PrEP scale-up for younger women aged 15–25, women aged 25–34, and women aged 35–49 years, while accounting for the low program retention levels reported in demonstration projects. Perhaps, counter-intuitively, it is shown that PrEP could substantially avert more infections a year amongst women in the general population than amongst female sex workers. In summary, our models and analysis could help decision makers effectively allocate resources to each of these prevention/treatment strategies amongst different sub-populations.