Optimizing infant HIV diagnosis with additional screening at immunization clinics in three sub‐Saharan African settings: a cost‐effectiveness analysis

IntroductionUptake of early infant HIV diagnosis (EID) varies widely across sub‐Saharan African settings. We evaluated the potential clinical impact and cost‐effectiveness of universal maternal HIV screening at infant immunization visits, with referral to EID and maternal antiretroviral therapy (ART) initiation.MethodsUsing the CEPAC‐Pediatric model, we compared two strategies for infants born in 2017 in Côte d’Ivoire (CI), South Africa (SA), and Zimbabwe: (1) existing EID programmes offering six‐week nucleic acid testing (NAT) for infants with known HIV exposure (EID), and (2) EID plus universal maternal HIV screening at six‐week infant immunization visits, leading to referral for infant NAT and maternal ART initiation (screen‐and‐test). Model inputs included published Ivoirian/South African/Zimbabwean data: maternal HIV prevalence (4.8/30.8/16.1%), current uptake of EID (40/95/65%) and six‐week immunization attendance (99/74/94%). Referral rates for infant NAT and maternal ART initiation after screen‐and‐test were 80%. Costs included NAT ($24/infant), maternal screening ($10/mother–infant pair), ART ($5 to 31/month) and HIV care ($15 to 190/month). Model outcomes included mother‐to‐child transmission of HIV (MTCT) among HIV‐exposed infants, and life expectancy (LE) and mean lifetime per‐person costs for children with HIV (CWH) and all children born in 2017. We calculated incremental cost‐effectiveness ratios (ICERs) using discounted (3%/year) lifetime costs and LE for all children. We considered two cost‐effectiveness thresholds in each country: (1) the per‐capita GDP ($1720/6380/2150) per year‐of‐life saved (YLS), and (2) the CEPAC‐generated ICER of offering 2 versus 1 lifetime ART regimens (e.g. offering second‐line ART; $520/500/580/YLS).ResultsWith EID, projected six‐week MTCT was 9.3% (CI), 4.2% (SA) and 5.2% (Zimbabwe). Screen‐and‐test decreased total MTCT by 0.2% to 0.5%, improved LE by 2.0 to 3.5 years for CWH and 0.03 to 0.07 years for all children, and increased discounted costs by $17 to 22/child (all children). The ICER of screen‐and‐test compared to EID was $1340/YLS (CI), $650/YLS (SA) and $670/YLS (Zimbabwe), below the per‐capita GDP but above the ICER of 2 versus 1 lifetime ART regimens in all countries.ConclusionsUniversal maternal HIV screening at immunization visits with referral to EID and maternal ART initiation may reduce MTCT, improve paediatric LE, and be of comparable value to current HIV‐related interventions in high maternal HIV prevalence settings like SA and Zimbabwe.     

How community ART delivery may improve HIV treatment outcomes: Qualitative inquiry into mechanisms of effect in a randomized trial of community‐based ART initiation,monitoring and re‐supply (DO ART) in South Africa and Uganda

IntroductionUNAIDS fast track targets for ending the AIDS epidemic by 2030 call for viral suppression in 95% of people using antiretroviral therapy (ART) to treat HIV infection. Difficulties in linking to care following a positive HIV test have impeded progress towards meeting treatment targets. Community‐based HIV services may reduce linkage barriers and have been associated with high retention and favourable clinical outcomes. We use qualitative data from The Delivery Optimization of Antiretroviral Therapy (DO ART) Study, a three‐arm randomized trial of community ART initiation, monitoring and re‐supply conducted in western Uganda and KwaZulu‐Natal South Africa, to identify mechanisms through which community ART delivery may improve treatment outcomes, defined as viral suppression in people living with HIV (PLHIV).MethodsWe conducted open‐ended interviews with a purposeful sample of 150 DO ART participants across study arms and study sites, from October 2016 to November 2019. Interviews covered experiences of: (1) HIV testing; (2) initiating and refilling ART; and (3) participating in the DO ART Study. A combined inductive content analytic and thematic approach was used to characterize mechanisms through which community delivery of ART may have contributed to viral suppression in the DO ART trial.ResultsThe analysis yielded four potential mechanisms drawn from qualitative data representing the perspectives and priorities of DO ART participants. Empowering participants to schedule, re‐schedule and select the locations of community‐based visits via easy phone contact with clinical staff is characterized as flexibility. Integration refers to combining the components of clinic‐based visits into single interaction with a healthcare provider. Providers” willingness to talk at length with participants during visits, addressing non‐HIV as well as HIV‐related concerns, is termed “a slower pace”. Finally, increased efficiency denotes the time savings and increased income‐generating opportunities for participants brought about by delivering services in the community.ConclusionsUnderstanding the mechanisms through which HIV service delivery innovations produce an effect is key to transferability and potential scale‐up. The perspectives and priorities of PLHIV can indicate actionable changes for HIV care programs that may increase engagement in care and improve treatment outcomes.     

24‐Month HIV‐free survival among HIV‐exposed Infants in Lesotho: the PEAWIL cohort study

IntroductionFollowing the implementation of the provision of lifelong antiretroviral therapy to all HIV‐positive pregnant or breastfeeding women for prevention of mother‐to‐child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24‐month HIV‐free survival among HIV‐exposed infants (HEIs).MethodsWe conducted a prospective observational cohort study that enrolled HIV‐positive and HIV‐negative pregnant women, with follow‐up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow‐up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV‐free survival rates were computed using Kaplan–Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death.ResultsBetween June 2014 and February 2016, we enrolled 653 HIV‐positive and 941 HIV‐negative pregnant women. Twenty‐seven HIV‐negative women acquired HIV during follow‐up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV‐unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24‐month follow‐up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow‐up, 17 were found to be HIV‐positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow‐up were HIV‐positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV‐positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24‐month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log‐rank p = 0.065). HIV‐free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants.ConclusionsThe implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts.     

Use of quality‐of‐life instruments for people living with HIV: a global systematic review and meta‐analysis

IntroductionDue to the effectiveness of combined antiretroviral therapy and its growing availability worldwide, most people living with HIV (PLHIV) have a near‐normal life expectancy. However, PLHIV continue to face various health and social challenges that severely impact their health‐related quality‐of‐life (HRQoL). The UNAIDS Global AIDS Strategy discusses the need to optimize quality‐of‐life, but no guidance was given regarding which instruments were appropriate measures of HRQoL. This study aimed to review and assess the use of HRQoL instruments for PLHIV.MethodsWe conducted a global systematic review and meta‐analysis, searching five databases for studies published between January 2010 and February 2021 that assessed HRQoL among PLHIV aged 16 years and over. Multivariable regression analyses were performed to identify factors associated with the choice of HRQoL instruments. We examined the domains covered by each instrument. Random‐effects meta‐analysis was conducted to explore the average completion rates of HRQoL instruments.Results and discussionFrom 714 publications, we identified 65 different HRQoL instruments. The most commonly used instruments were the World Health Organization Quality‐of‐Life‐ HIV Bref (WHOQOL‐HIV BREF)—19%, Medical Outcome Survey‐HIV (MOS‐HIV)—17%, Short Form‐36 (SF‐36)—12%, European Quality‐of‐Life Instrument‐5 Dimension (EQ‐5D)—10%, World Health Organization Quality‐of‐Life Bref (WHOQOL BREF)—8%, Short Form‐12 (SF‐12)—7% and HIV/AIDS Targeted Quality‐of‐Life (HAT‐QOL)—6%. There were greater odds of using HIV‐specific instruments for middle‐ and low‐income countries (than high‐income countries), studies in the Americas and Europe (than Africa) and target population of PLHIV only (than both PLHIV and people without HIV). Domains unique to the HIV‐specific instruments were worries about death, stigma and HIV disclosure. There were no significant differences in completion rates between different HRQoL instruments. The overall pooled completion rate was 95.9% (95% CI: 94.7−97.0, I ² = 99.2%, p < 0.01); some heterogeneity was explained by country‐income level and study type.ConclusionsA wide range of instruments have been used to assess HRQoL in PLHIV, and the choice of instrument might be based on their different characteristics and reason for application. Although completion rates were high, future studies should explore the feasibility of implementing these instruments and the appropriateness of domains covered by each instrument.     

Intersecting stigma and HIV testing practices among urban refugee adolescents and youth in Kampala,Uganda: qualitative findings

IntroductionHIV‐related risks may be exacerbated in humanitarian contexts. Uganda hosts 1.3 million refugees, of which 60% are aged under 18. There are knowledge gaps regarding HIV testing facilitators and barriers, including HIV and intersecting stigmas, among urban refugee youth. In response, we explored experiences and perspectives towards HIV testing strategies, including HIV self‐testing, with urban refugee youth in Kampala, Uganda.MethodsWe implemented a qualitative study with refugee cisgender youth aged 16 to 24 living in Kampala''s informal settlements from February‐April 2019. We conducted five focus groups with refugee youth, including two with adolescent boys and young men, two with adolescent girls and young women and one with female sex workers. We also conducted five key informant (KI) interviews with government, non‐government and community refugee agencies and HIV service providers. We conducted thematic analyses to understand HIV testing experiences, perspectives and recommendations.ResultsParticipants (n = 49) included young men (n = 17) and young women (n = 27) originally from the Democratic Republic of Congo [DRC] (n = 29), Rwanda (n = 11), Burundi (n = 3) and Sudan (n = 1), in addition to five KI (gender: n = 3 women, n = 2 men; country of origin: n = 2 Rwanda, n = 2 Uganda, n = 1 DRC). Participant narratives revealed stigma drivers included fear of HIV infection; misinformation that HIV is a “Ugandan disease”; and blame and shame for sexual activity. Stigma facilitators included legal precarity regarding sex work, same‐sex practices and immigration status, alongside healthcare mistreatment and confidentiality concerns. Stigma experiences were attributed to the social devaluation of intersecting identities (sex work, youth, refugees, sexual minorities, people living with HIV, women). Participants expressed high interest in HIV self‐testing. They recommended HIV self‐testing implementation strategies to be peer supported and expressed concerns regarding sexual‐ and gender‐based violence with partner testing.ConclusionsIntersecting stigma rooted in fear, misinformation, blame and shame, legal precarity and healthcare mistreatment constrain current HIV testing strategies with urban refugee youth. Findings align with the Health Stigma and Discrimination Framework that conceptualizes stigma drivers and facilitators that devalue intersecting health conditions and social identities. Findings can inform multi‐level strategies to foster enabling HIV testing environments with urban refugee youth, including tackling intersecting stigma and leveraging refugee youth peer support.     

“It's a burden,it's a nuisance. I wish I didn't have these other ailments”: a qualitative exploration of comorbidities management among older people living with HIV who use drugs in Vancouver,British Columbia

IntroductionPeople living with HIV (PLHIV) who use illicit drugs (other than or in addition to cannabis) are living longer due to antiretroviral therapy (ART). Older PLHIV who use drugs have an increased risk for comorbidities, and managing multiple health conditions is a growing concern among this population. However, in‐depth understandings of the lived realities and complexities of living with HIV alongside comorbidities among older PLHIV who use drugs remain limited. We sought to explore how older PLHIV who use drugs manage their comorbid conditions in a setting with universal ART access.MethodsBetween January 2019 and March 2020, semi‐structured, in‐depth interviews were conducted in Vancouver, Canada with 42 older PLHIV who use drugs and were living with at least one comorbidity. All participants were currently on ART, and had initiated treatment at least 2 years prior to the interviews. Data were analysed using inductive and deductive approaches.ResultsSeveral themes were identified through this analysis. First, comorbidities were perceived as more urgent health concerns and prioritized over HIV. Second, stigma and discrimination hindered access to care for comorbidities. Third, the concurrent management of HIV and comorbidities was often challenging due to unmanaged or poorly managed comorbidities. Fourth, the potential impact of ART on the development of comorbidities was a source of concern and frustration. Finally, integrated treatment approaches facilitated engagement with HIV and comorbidities care.ConclusionsOur findings underscore the need for HIV care to shift from a primary focus on managing HIV to an integrated, patient‐centred approach that addresses both HIV and non‐HIV‐related health needs, as well as an equitable and non‐judgemental delivery of such care for an ageing population of PLHIV who use drugs.     

Improved detection and management of advanced HIV disease through a community adult TB‐contact tracing intervention with same‐day provision of the WHO‐recommended package of care including ART initiation in a rural district of Mozambique

IntroductionAIDS‐mortality remains unacceptably high in sub‐Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact‐tracing intervention (Xpatial‐TB). The aim was to assess the burden of AHD among high‐risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO‐recommended package of care to this population.MethodsAll PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial‐TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/μL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB‐lipoarabinomannan (TB‐LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow‐up visits carried out under routine programmatic conditions for six months.ResultsA total of 2881 adults were identified in the Xpatial TB‐contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB‐contacts) consented to the study and were screened for AHD. Seventy percent of TB index‐patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum‐CrAg was positive in 4.6% (4/87) of TB‐index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six‐month mortality was 21% among TB‐index cases and zero in TB contacts.ConclusionsA TB contact‐tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO‐recommended package of care in this rural Mozambican population. Same‐day and accelerated ART initiation was feasible and safe in this population including among those with AHD.     

The impact of disruptions due to COVID‐19 on HIV transmission and control among men who have sex with men in China

IntroductionThe COVID‐19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV‐related mortality. We estimated how COVID‐19‐related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one‐ and five‐year time horizon.MethodsRegional data from China indicated that the number of MSM undergoing facility‐based HIV testing reduced by 59% during the COVID‐19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV‐related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6‐month disruption periods, starting from 1 January 2020.ResultsOur model predicted new HIV infections and HIV‐related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three‐month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 decrease).ConclusionsThe overall impact of COVID‐19 on new HIV infections and HIV‐related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID‐19‐related disruption on HIV transmission and control among MSM in China.     

Weight changes after antiretroviral therapy initiation in CoRIS (Spain): a prospective multicentre cohort study

IntroductionWeight gain after starting antiretroviral therapy (ART) is a major problem that can increase morbidity. Our main objective was to evaluate the effects of initial ART on weight change in a large prospective cohort of HIV‐positive individuals.MethodsThis was a prospective cohort study of 13,198 subjects included in the Spanish HIV Research Network (CoRIS) between January 2004 and November 2018. We included subjects who started triple ART and achieved HIV RNA suppression within 48 weeks. We fitted linear mixed models adjusted for potential confounders to compare longitudinal changes in weight. We used Cox proportional‐hazard models to compare treatment groups’ times to transition to a higher body mass index (BMI) category.ResultsWe analysed data from a total of 1631 individuals resulting in 14,965 persons/years and 14,085 observations. Individuals retained in the final multivariable model were representative of the overall cohort. NNRTI‐based first‐line ART was associated with a lower average weight gain compared to PI‐ (+0.7 kg per year, 95% CI 0.5 to 1.0, p < 0.001) and INSTI‐based (+0.9 kg per year, 95% CI 0.7 to 1.1, p < 0.001) regimens. Individuals starting ART with TAF+FTC had greater weight gain than those receiving TDF+FTC (+0.8 kg per year, 95% CI 0.3 to 1.4, p = 0.004). Women and black persons presented a greater weight gain than men and non‐black individuals. Differences in weight trajectories were driven mainly by changes during the first year of ART. The NNRTI group was less likely to transition from normal weight to overweight than the PI (aHR 1.48, 95% CI 1.18 to 1.85) and INSTI groups (aHR 1.30, 95% CI 1.03 to 1.64). PIs but not INSTIs were associated with a higher rate of overweight‐to‐obesity shift (aHR 2.17, 95% CI 1.27 to 3.72). No differences were found among INSTIs in the transition to a higher BMI category.ConclusionsINSTI‐ and PI‐based first‐line ARTs are associated with greater weight gain compared to NNRTI‐based ART. Within the NRTIs, TAF+FTC was most strongly associated with weight gain. This heterogeneous effect of ART on body weight could affect the long‐term risk of some non‐communicable diseases.     

Annual home‐based HIV testing in the Chókwè Health Demographic Surveillance System,Mozambique, 2014 to 2019: serial population‐based survey evaluation

IntroductionWHO recommends implementing a mix of community and facility testing strategies to diagnose 95% of persons living with HIV (PLHIV). In Mozambique, a country with an estimated 506,000 undiagnosed PLHIV, use of home‐based HIV testing services (HBHTS) to help achieve the 95% target has not been evaluated.MethodsHBHTS was provided at 20,000 households in the Chókwè Health Demographic Surveillance System (CHDSS), Mozambique, in annual rounds (R) during 2014 to 2019. Trends in prevalence of HIV infection, prior HIV diagnosis among PLHIV (diagnostic coverage), and undiagnosed HIV infection were assessed with three population‐based surveys conducted in R1 (04/2014 to 04/2015), R3 (03/2016 to 12/2016), and R5 (04/2018 to 03/2019) of residents aged 15 to 59 years. Counts of patients aged ≥15 years tested for HIV in CHDSS healthcare facilities were obtained from routine reports.ResultsDuring 2014 to 2019, counsellors conducted 92,512 home‐based HIV tests and newly diagnosed 3711 residents aged 15 to 59 years. Prevalence of HIV infection was stable (R1, 25.1%; R3 23.6%; R5 22.9%; p‐value, 0.19). After the first two rounds (44,825 home‐based tests; 31,717 facility‐based tests), diagnostic coverage increased from 73.8% (95% CI 70.3 to 77.2) in R1 to 93.0% (95% CI 91.3 to 94.7) in R3, and prevalence of undiagnosed HIV infection decreased from 6.6% (95% CI 5.6 to 7.5) in R1 to 1.7% (95% CI 1.2 to 2.1) in R3. After two more rounds (32,226 home‐based tests; 46,003 facility‐based tests), diagnostic coverage was 95.4% (95% CI 93.7 to 97.1) and prevalence of undiagnosed HIV infection was 1.1% (95% CI 0.7 to 1.5) in R5. Prevalence of having last tested at home was 12.7% (95% CI 11.3 to 14.0) in R1, 45.2% (95% CI 43.4 to 47.0) in R3, and 41.4% (95% CI 39.5 to 43.2) in R5, and prevalence of having last tested at a healthcare facility was 45.3% (95% CI 43.3 to 47.3) in R1, 40.1% (95% CI 38.4 to 41.8) in R3, and 45.2% (95% CI 43.3 to 47.0) in R5.ConclusionsHBHTS successfully augmented facility‐based testing to achieve HIV diagnostic coverage in a high‐burden community of Mozambique. HBHTS should be considered in sub‐Saharan Africa communities striving to diagnose 95% of persons living with HIV.     

Cost‐effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States

BackgroundExpanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States.MethodsWe developed a microsimulation model that randomly selected (with replacement) individuals from the Data‐collection on Adverse Effects of Anti‐HIV Drugs study with follow‐up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid‐lowering therapy. Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness‐to‐pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual’s probability of experiencing atherosclerotic cardiovascular disease over 20 years.ResultsPersons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost‐effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost‐effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal.ConclusionsPravastatin was projected to be cost‐effective compared with no statin. With substantial price reduction, pitavastatin may be cost‐effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV‐specific estimates on the efficacy of statins and the quality‐of‐life burden associated with taking an additional daily pill.     

HIV testing and linkage to ART following secondary distribution of HIV self‐test kits to male partners of women living with HIV: a pilot randomized control trial in Mpumalanga,South Africa

IntroductionSouth African men are underrepresented in HIV testing and treatment services. Secondary distribution of oral HIV self‐test (HIVST) kits by women living with HIV (WLHIV) to their male partners (i.e. index partner HIVST) may increase men''s testing and treatment but has been understudied.MethodsBetween March and July 2021, we evaluated the effectiveness of index partner HIVST versus the standard of care (SOC) (invitations for men''s facility‐based testing) on men''s testing in a 1:1 randomized control trial. Eligibility criteria included: WLHIV; ≥18 years of age; attending one of four high‐density rural clinics; have a working cell phone; and self‐reported having a primary male partner of unknown serostatus. The primary outcome was the proportion of WLHIV reporting that her partner tested for HIV within 3 months after enrolment.ResultsWe enrolled 180 WLHIV and 176 completed an endline survey (mean age = 35 years, 15% pregnant, 47% unmarried or non‐cohabiting). In the HIVST arm, 78% of male partners were reported to have tested for HIV versus 55% in SOC (RR = 1.41; 95% CI = 1.14–1.76). In the HIVST arm, nine men were reactive with HIVST (14% positivity), six were confirmed HIV positive with standard testing (67%) and all of those started antiretroviral therapy (ART), and four HIV‐negative men started pre‐exposure prophylaxis (PrEP) (5%). In SOC, six men were diagnosed with HIV (12% positivity), 100% started ART and seven HIV‐negative men started PrEP (16%). One case of verbal intimate partner violence was reported in the HIVST arm.ConclusionsSecondary distribution of HIVST to partners of WLHIV was acceptable and effective for improving HIV testing among men in rural South Africa in our pilot study. Interventions are needed to link reactive HIVST users to confirmatory testing and ART.     

Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation

IntroductionMany children living with HIV (CLWH) display impaired cognition. Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long‐term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART‐Def; n = 22); immediate time‐limited ART for 40 weeks (ART‐40W; n = 30) and immediate time‐limited ART for 96 weeks (ART‐96W; n = 18). We also recruited HIV‐exposed uninfected (CHEU; n = 28) and HIV‐unexposed (CHU; n = 35) children.MethodsData were collected between May 2012 and December 2017. Mixed‐model repeated‐measures ANOVAs assessed differences over time between CLWH (ART‐40W, ART‐96W and ART‐Def) and CHIV‐ CHEU and CHU between ART‐Early (ART‐40W and ART‐96W), ART‐Def, CHEU and CHU; and between ART‐40W, ART‐96W, ART‐Def, CHEU and CHU.ResultsAll comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps < 0.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV‐ at seven years (p < 0.001) but improved to equivalence at nine years, (b) visual‐spatial processing and problem solving, only CLWH (p < 0.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV‐ at both seven and nine years (p = 0.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART‐Early and CHEU (p < 0.01 and <0.04), and (b) motor dexterity, ART‐Def performed worse than ART‐Early, CHEU and CHU at seven years (p = 0.02, <0.001 and <0.001 respectively) but improved to equivalence at nine years (ps > 0.17). Similarly, for motor dexterity, ART‐Def performed worse than ART‐96W, CHEU and CHU at seven years (p < 0.04, <0.001 and <0.001) but improved to equivalence at nine years (ps > 0.20).ConclusionsAlthough neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART‐treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children’s future learning, reasoning and adaptive functioning.     

Trends in demographic and clinical characteristics and initiation of antiretroviral therapy among adult patients enrolling in HIV care in the Central Africa International epidemiology Database to Evaluate AIDS (CA‐IeDEA) 2004 to 2018

IntroductionThe Central Africa International epidemiology Database to Evaluate AIDS (CA‐IeDEA) is an open observational cohort study investigating impact, progression and long‐term outcomes of HIV/AIDS among people living with HIV (PLWH) in Burundi, Cameroon, Democratic Republic of Congo (DRC), Republic of Congo (ROC) and Rwanda. We describe trends in demographic, clinical and immunological characteristics as well as antiretroviral therapy (ART) use of patients aged > 15 years entering into HIV care in the participating CA‐IeDEA site.MethodsInformation on sociodemographic characteristics, height, weight, body mass index (BMI), CD4 cell count, WHO staging and ART status at entry into care from 2004 through 2018 were extracted from clinic records of patients aged > 15 years enrolling in HIV care at participating clinics in Burundi, Cameroon, DRC, ROC and Rwanda. We assessed trends in patient characteristics at enrolment in HIV care including ART initiation within the first 30 days after enrolment in care and calculated proportions, means and medians (interquartile ranges) for the main variables of interest.ResultsAmong 69,176 patients in the CA‐IeDEA cohort, 39% were from Rwanda, 24% from ROC, 18% from Cameroon, 14% from Burundi and 5% from DRC. More women (66%) than men enrolled in care and subsequently initiated ART. Women were also younger than men (32 vs. 38 years, P < 0.001) at enrolment and at ART initiation. Trends over time show increases in median CD4 cell count at enrolment from 190 cells/µL in 2004 to 334 cells/µL in 2018 at enrolment. Among those with complete data on CD4 counts (60%), women had a higher median CD4 cell count at care entry than men (229 vs. 249 cells/µL, P < 0.001). Trends in the proportion of patients using ART within 30 days of enrolment at the participating site show an increase from 16% in 2004 to 75% in 2018.ConclusionsTrends from 2004 to 2018 in the characteristics of patients participating in the CA‐IeDEA cohort highlight improvements at entry into care and subsequent ART initiation including after the implementation of Treat All guidelines in the participating sites.     

A cluster‐randomized controlled trial to improve the quality of integrated HIV‐tuberculosis services in primary healthcareclinics in South Africa

Introduction: Tuberculosis (TB) remains the most common cause of death among people living with HIV. Integrating HIV and TB services reduces mortality but is sub‐optimally implemented. Quality improvement (QI) methods offer a low‐cost and easily implementable approach to strengthening healthcare delivery systems. This trial assessed a QI intervention on key process indicators for delivering integrated HIV‐TB care in rural South African primary healthcare (PHC) clinics.MethodsSixteen nurse supervisors, (each with a cluster of clinics) overseeing 40 PHC clinics, were randomized 1:1 to the intervention or the standard of care (SOC) groups. The QI intervention comprised three key components: clinical and QI skills training, on‐site mentorship of nurse supervisors and clinic staff, and data quality improvement activities to enhance accuracy and completeness of routine clinic data. The SOC comprised monthly supervision and data feedback meetings. From 01 December 2016 to 31 December 2018, data were collected monthly by a team of study‐appointed data capturers from all study clinics. This study''s outcomes were HIV testing services (HTS), TB screening, antiretroviral therapy (ART) initiation, isoniazid preventive therapy (IPT) initiation and viral load (VL) testing.ResultsThe QI group (eight clusters) comprised 244 clinic staff who attended to 13,347 patients during the trial compared to the SOC group (eight clusters) with 217 clinic staff who attended to 8141 patients. QI mentors completed 85% (510/600) of expected QI mentorship visits to QI clinics. HTS was 19% higher [94.5% vs. 79.6%; relative risk (RR)=1.19; 95% CI: 1.02–1.38; p=0.029] and IPT initiation was 66% higher (61.2 vs. 36.8; RR=1.66; 95% CI: 1.02–2.72; p=0·044), in the QI group compared to SOC group. The percentage of patients screened for TB (83.4% vs. 79.3%; RR=1.05; p=0.448), initiated on ART (91.7 vs. 95.5; RR=0.96; p=0.172) and VL testing (72.2% vs. 72.8%; RR=0.99; p=0.879) was similar in both groups.ConclusionsQI improved HIV testing and IPT initiation compared to SOC. TB screening, ART initiation and VL testing remained similar. Incorporating QI methods into routine supervision and support activities may strengthen integrated HIV‐TB service delivery and increase the success of future QI scale‐up activities.     

The efficacy and cost‐effectiveness of a family‐based economic empowerment intervention (Suubi + Adherence) on suppression of HIV viral loads among adolescents living with HIV: results from a Cluster Randomized Controlled Trial in southern Uganda

IntroductionEvidence from low‐resource settings indicates that economic insecurity is a major barrier to HIV treatment adherence. Economic empowerment (EE) interventions have the potential to improve adherence outcomes among adolescents living with HIV (ALWHIV) by mitigating the effects of poverty. This study aims to assess the efficacy and cost‐effectiveness of a savings‐led family‐based EE intervention, Suubi + Adherence, aimed at improving antiretroviral therapy (ART) adherence outcomes ALWHIV in Uganda.MethodsAdolescents (mean age 12 years at enrolment; 56% female) receiving ART for HIV at 39 health centres were randomized to Suubi + Adherence intervention (n = 358) or bolstered standard of care (BSOC; n = 344). A difference‐in‐differences analysis was employed to assess the change in the proportion of virally suppressed adolescents (HIV RNA viral load <40 copies/mL) over 24 months. The cost‐effectiveness analysis examined how much the intervention cost to virally suppress one additional adolescent relative to BSOC from the healthcare provider perspective.ResultsAt 24 months, the intervention was associated with an 8.85‐percentage point [95% confidence interval (CI) 0.80 to 16.90 percentage points] increase in the proportion of virally suppressed adolescents between the study arms (p = 0.032). Per‐participant costs were US$177 and US$263 for the BSOC and intervention groups respectively. The incremental cost of virally suppressing one additional adolescent was estimated at US$970 [95% CI, US$508 to 10,725] over two years.ConclusionsOur results support the integration of family‐based EE interventions into adherence‐support strategies as part of routine HIV care in low‐resource settings to address the underlying economic drivers of poor ART adherence among ALWHIV. Moreover, per‐participant costs to achieve viral suppression do not seem prohibitive compared to other community‐based adherence interventions targeted at ALWHIV in low‐resource settings. Further research on combination interventions at the nexus of economic security and HIV treatment and care is needed to inform the development of feasible and scalable HIV policies and programmes.     

The likelihood of severe COVID‐19 outcomes among PLHIV with various comorbidities: a comparative frequentist and Bayesian meta‐analysis approach

IntroductionThe SARS‐CoV‐2 virus can currently pose a serious health threat and can lead to severe COVID‐19 outcomes, especially for populations suffering from comorbidities. Currently, the data available on the risk for severe COVID‐19 outcomes due to an HIV infection with or without comorbidities paint a heterogenous picture. In this meta‐analysis, we summarized the likelihood for severe COVID‐19 outcomes among people living with HIV (PLHIV) with or without comorbidities.MethodsFollowing PRISMA guidelines, we utilized PubMed, Web of Science and medRxiv to search for studies describing COVID‐19 outcomes in PLHIV with or without comorbidities up to 25 June 2021. Consequently, we conducted two meta‐analyses, based on a classic frequentist and Bayesian perspective of higher quality studies.Results and discussionWe identified 2580 studies (search period: January 2020–25 June 2021, data extraction period: 1 January 2021–25 June 2021) and included nine in the meta‐analysis. Based on the frequentist meta‐analytical model, PLHIV with diabetes had a seven times higher risk of severe COVID‐19 outcomes (odd ratio, OR = 6.69, 95% CI: 3.03–19.30), PLHIV with hypertension a four times higher risk (OR = 4.14, 95% CI: 2.12–8.17), PLHIV with cardiovascular disease an odds ratio of 4.75 (95% CI: 1.89–11.94), PLHIV with respiratory disease an odds ratio of 3.67 (95% CI: 1.79–7.54) and PLHIV with chronic kidney disease an OR of 9.02 (95% CI: 2.53–32.14) compared to PLHIV without comorbidities. Both meta‐analytic models converged, thereby providing robust summative evidence. The Bayesian meta‐analysis produced similar effects overall, with the exclusion of PLHIV with respiratory diseases who showed a non‐significant higher risk to develop severe COVID‐19 outcomes compared to PLHIV without comorbidities.ConclusionsOur meta‐analyses show that people with HIV, PLHIV with coexisting diabetes, hypertension, cardiovascular disease, respiratory disease and chronic kidney disease are at a higher likelihood of developing severe COVID‐19 outcomes. Bayesian analysis helped to estimate small sample biases and provided predictive likelihoods. Clinical practice should take these risks due to comorbidities into account and not only focus on the HIV status alone, vaccination priorities should be adjusted accordingly.     

Home‐Based Intervention to Test and Start (HITS): a community‐randomized controlled trial to increase HIV testing uptake among men in rural South Africa

IntroductionThe uptake of HIV testing and linkage to care remains low among men, contributing to high HIV incidence in women in South Africa. We conducted the “Home‐Based Intervention to Test and Start” (HITS) in a 2x2 factorial cluster randomized controlled trial in one of the World’s largest ongoing HIV cohorts in rural South Africa aimed at enhancing both intrinsic and extrinsic motivations for HIV testing.MethodsBetween February and December 2018, in the uMkhanyakude district of KwaZulu‐Natal, we randomly assigned 45 communities (clusters) (n = 13,838 residents) to one of the four arms: (i) financial incentives for home‐based HIV testing and linkage to care (R50 [$3] food voucher each); (ii) male‐targeted HIV‐specific decision support application, called EPIC‐HIV; (iii) both financial incentives and male‐targeted HIV‐specific decision support application and (iv) standard of care (SoC). EPIC‐HIV was developed to encourage and serve as an intrinsic motivator for HIV testing and linkage to care, and individually offered to men via a tablet device. Financial incentives were offered to both men and women. Here we report the effect of the interventions on uptake of home‐based HIV testing among men. Intention‐to‐treat (ITT) analysis was performed using modified Poisson regression with adjustment for clustering of standard errors at the cluster levels.ResultsAmong all 13,838 men ≥ 15 years living in the 45 communities, the overall population coverage during a single round of home‐based HIV testing was 20.7%. The uptake of HIV testing was 27.5% (683/2481) in the financial incentives arm, 17.1% (433/2534) in the EPIC‐HIV arm, 26.8% (568/2120) in the arm receiving both interventions and 17.8% in the SoC arm. The probability of HIV testing increased substantially by 55% in the financial incentives arm (risk ratio (RR)=1.55, 95% CI: 1.31 to 1.82, p < 0.001) and 51% in the arm receiving both interventions (RR = 1.51, 95% CI: 1.21 to 1.87 p < 0.001), compared to men in the SoC arm. The probability of HIV testing did not significantly differ in the EPIC‐HIV arm (RR = 0.96, 95% CI: 0.76 to 1.20, p = 0.70).ConclusionsThe provision of a small financial incentive acted as a powerful extrinsic motivator substantially increasing the uptake of home‐based HIV testing among men in rural South Africa. In contrast, the counselling and testing application which was designed to encourage and serve as an intrinsic motivator to test for HIV did not increase the uptake of home‐based testing.