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As a result of massive scale-up efforts in developing countries, millions of people living with HIV are now receiving antiretroviral therapy (ART). However, countries have been uneven in their scale-up efforts with ART coverage rates exceeding expectations in some places and lagging behind expectation in others. This paper develops a model that explains ART scale-up as a function of the responsiveness of political parties to their primary constituents. Specifically, the paper argues that, faced with a perilous ‘threat to the nation’, countries responded in one of two ways, both of which were designed to appeal to their primary constituents – either adopting a ‘Geneva Consensus’ response, or depicting the epidemic as a Western disease and adopting a ‘pan-African’ response. The article tests this theory using Afrobarometer data for eleven countries. The paper finds that HIV/AIDS is generally a non-partisan issue in most countries. However, the analysis does uncover some differences in partisan support for HIV/AIDS responses in both countries that have adopted Geneva Consensus and pan-African responses, though not in the direction hypothesised. The lack of congruence in policy preferences between the public and their governments suggests a democratic deficit in that these governments have acted independently of the preferences of core constituents. [ABSTRACT FROM AUTHOR]

As universal testing moves onto the HIV agenda, there is a need for more understanding of the relatively low uptake of HIV testing and the dynamics of disclosure in Sub-Saharan Africa. Despite the expanding provision of anti-retroviral therapy in Zambia since 2004, disclosure of HIV status - beyond a closed network - remains limited. Drawing on 20 years of living and working in a high HIV prevalence country, research on HIV-related stigma and existing literature on disclosure, this paper explores the reasons that lie behind limited disclosure. Unravelling why HIV disclosure remains 'a navigation in a moral field', the pattern of silence around HIV and the routine and often subtle presence of HIV in daily life reveals two key dynamics. The first dynamic is shifting public/private boundaries and retaining a wider identity. People living with HIV juggle the pragmatic advantages of disclosing to a limited circle with the importance of maintaining not only their moral integrity, status and (for some) professional and group identity but also of maintaining their privacy. A more public disclosure ('speaking it' more widely) shifts private-public boundaries and can be threatening, dangerous and can fix identity. Furthermore, disclosure carries obligations which, given high levels of poverty, can be hard to meet. The second dynamic is a pattern of implicit understanding. It can be easier in a context of high HIV prevalence to opt for silence, in its various forms, with the presence of HIV implicitly understood but not often explicitly spoken about. Although this gives more room for manoeuvre and for respect, silence too can be dangerous and certain situations dictate that it is better to breach the silence. More aggressive promotion of HIV testing needs to both respect and consider how to work within these existing dynamics to facilitate safe disclosure. [ABSTRACT FROM AUTHOR]

Currently, <10% of all HIV-infected children who need anti-retroviral therapy in sub-Saharan Africa are actually receiving therapy. Many constraints prevent these children from gaining access to appropriate care, including the magnitude of the paediatric epidemic, competing interests of adult care, health system inadequacies, technical challenges and patient-related factors. These issues form the basis of this paper which discusses the practical challenges of extending optimal care to all deserving children. Besides the need for major human, infrastructural, technical and logistic investments to overcome existing constraints, more clinical research is required before treatment guidelines can be refined in resource-constrained settings. In this regard, the paper lists some important research questions that should be addressed. [ABSTRACT FROM AUTHOR]

Background: A systematic review of randomised trials may be conclusive signalling no further research is needed; or identify gaps requiring further research that may then be included in review updates. In qualitative evidence synthesis (QES), the rationale, triggers, and methods for updating are less clear cut. We updated a QES on adherence to anti-retroviral treatment to examine if thematic saturation renders additional research redundant. Methods: We adopted the original review search strategy and eligibility criteria to identify studies in the subsequent three years. We assessed studies for conceptual detail, categorised as 'rich' or 'sparse', coding the rich studies. We sought new codes, and appraised whether findings confirmed, extended, enriched, or refuted existing themes. Finally, we examined if the analysis impacted on the original conceptual model. Results: After screening 3895 articles, 301 studies met the inclusion criteria. Rich findings from Africa were available in 82 studies; 146 studies were sparse, contained no additional information on specific populations, and did not contribute to the analysis. New studies enriched our understanding on the relationship between external and internal factors influencing adherence, confirming, extending and enriching the existing themes. Despite careful evaluation of the new literature, we did not identify any new themes, and found no studies that refuted our theory. Conclusions: Updating an existing QES using the original question confirmed and sometimes enriched evidence within themes but made little or no substantive difference to the theory and overall findings of the original review. We propose this illustrates thematic saturation. We propose a thoughtful approach before embarking on a QES update, and our work underlines the importance of QES priority areas where further primary research may help, and areas where further studies may be redundant. [ABSTRACT FROM AUTHOR]

Simple Summary: Following infection with HIV, individuals are immunocompromised. Their weakened immune system puts them at a higher risk of certain cancers like Kaposi sarcoma and lymphoma. Even with antiretroviral therapy for HIV infection, these cancers remain common in developing countries, while in developed countries, there is a decline in some cancers but an increase in deaths from others. This review explores why these cancers happen in people with HIV and finds that the current treatment is not enough to prevent them. Understanding these reasons is crucial to improving the diagnosis and treatment of both HIV and its associated cancers, highlighting the need for more research to tackle this ongoing health issue. The immune deficiency associated with human immunodeficiency virus (HIV) infection causes a distinct increased risk of developing certain cancer types. Kaposi sarcoma (KS), invasive cervical cancer and non-Hodgkin's lymphoma (NHL) are the prominent malignancies that manifest as a result of opportunistic viral infections in patients with advanced HIV infection. Despite the implementation of antiretroviral therapy (ART), the prevalence of these acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) remains high in developing countries. In contrast, developed countries have experienced a steady decline in the occurrence of these cancer types. However, there has been an increased mortality rate attributed to non-ADMs. Here, we provide a review of the molecular mechanisms that are responsible for the development of ADMs and non-ADMs which occur in HIV-infected individuals. It is evident that ART alone is not sufficient to fully mitigate the potential for ADMs and non-ADMs in HIV-infected individuals. To enhance the diagnosis and treatment of both HIV and malignancies, a thorough comprehension of the mechanisms driving the development of such cancers is imperative. [ABSTRACT FROM AUTHOR]

This study aims to describe and understand the relationship between sociodemographic factors and PrEP awareness, and willingness to use a PrEP modality (oral or injectable).Despite the availability of effective prevention tools such as HIV preexposure prophylaxis (PrEP), African immigrants in the United States are disproportionately affected by HIV. Although PrEP can significantly reduce HIV infection in this population, research evidence on PrEP outcomes, such as awareness, knowledge, and willingness to use, is extremely limited. Between April and May 2022, 92 participants completed an online survey assessing their awareness, knowledge, and willingness to use oral or injectable PrEP. The association between sociodemographic characteristics and PrEP-related measures was examined using descriptive and Pearson's chi-squared or Fisher's exact tests. Participants (N = 92) were born between 1990 and 1999 (46.7%), female (70.76%) and highly educated (59.6%). About 52.2% were unaware of PrEP, and 65.6% were willing to use a PrEP modality. Findings indicate that individuals who reported being aware of PrEP demonstrated a high level of knowledge regarding the medication. Having a healthcare provider was associated with PrEP awareness and willingness to use, while educational status was associated with PrEP awareness. 51.1% of participants were willing to use an oral pill for prevention and 47.8% were willing to use injectable PrEP. Our findings highlight the need for PrEP-related research and interventions for African immigrants to increase awareness and provide options for HIV prevention, as African immigrants are currently not well-represented in PrEP delivery systems in the US. [ABSTRACT FROM AUTHOR]

Background: The rollout of antiretroviral therapy in sub-Saharan Africa has brought lifesaving treatment to millions of HIVinfected individuals. Treatment is lifelong, however, and to continue to benefit, patients must remain in care. Despite this, systematic investigations of retention have repeatedly documented high rates of loss to follow-up from HIV treatment programs. This paper introduces an explanation for missed clinic visits and subsequent disengagement among patients enrolled in HIV treatment and care programs in Africa. Methods and Findings: Eight-hundred-ninety patients enrolled in HIV treatment programs in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda who had extended absences from care were tracked for qualitative research interviews. Two-hundred-eighty-seven were located, and 91 took part in the study. Interview data were inductively analyzed to identify reasons for missed visits and to assemble them into a broader explanation of how missed visits may develop into disengagement. Findings reveal unintentional and intentional reasons for missing, along with reluctance to return to care following an absence. Disengagement is interpreted as a process through which missed visits and ensuing reluctance to return over time erode patients' subjective sense of connectedness to care. Conclusions: Missed visits are inevitable over a lifelong course of HIV care. Efforts to prevent missed clinic visits combined with moves to minimize barriers to re-entry into care are more likely than either approach alone to keep missed visits from turning into long-term disengagement. [ABSTRACT FROM AUTHOR]

With availability of antiretroviral treatments, HIV is increasingly recognised as a chronic disease people live with for many years. This paper critically reviews the current literature on fertility desires and reproductive intentions among people living with HIV/AIDS (PLHIV) and critiques the theoretical frameworks and methodologies used. A systematic review was conducted using electronic databases: ISI Web of Knowledge, Science Direct, Proquest, Jstor and CINAHL for articles published between 1990 and 2008. The search terms used were fertility desire, pregnancy, HIV, reproductive decision making, reproductive intentions, motherhood, fatherhood and parenthood. Twenty-nine studies were reviewed. Fertility desires were influenced by a myriad of demographic, health, stigma-associated and psychosocial factors. Cultural factors were also important, particularly in Sub-Saharan Africa and Asia. Future research that examines fertility desires among PLHIV should include cultural beliefs and practices in the theoretical framework in order to provide a holistic understanding and to enable development of services that meet the reproductive needs of PLHIV. [ABSTRACT FROM AUTHOR]

Background: The roll-out of antiretroviral therapy (ART) in Africa will have significant resource implications arising from its impact on demand for healthcare services. Existing studies of healthcare utilization on HAART have been conducted in the developed world, where HAART is commenced when HIV illness is less advanced. Methods: This paper describes healthcare utilization from program entry by treatment-naïve patients in a peri- urban settlement in South Africa. Treatment criteria included a CD4 cell count <200 cells/μl or an AIDS-defining illness. Data on health service utilization were collected retrospectively from the primary-care clinic and secondary and tertiary referral hospitals. Hospital visits were reviewed to determine the clinical reason for each visit. Results: 212 patients were followed for a median of 490 days. Outpatient visits per 100 patient years of observation (PYO), excluding scheduled primary-care follow-up, fell from 596 immediately prior to ART to 334 in the first 48 weeks on therapy and 245 thereafter. Total inpatient time fell from 2,549 days per 100 PYO pre-ART to 476 in the first 48 weeks on therapy and 73 thereafter. This fall in healthcare utilization occurred at every level of care. The greatest causes of utilization were tuberculosis, cryptococcal meningitis, HIV-related neoplasms and adverse reactions to stavudine. After 48 weeks on ART demand reverted to primarily non-HIV-related causes. Conclusion: Utilization of both inpatient and outpatient hospital services fell significantly after commencement of ART for South African patients in the public sector, with inpatient demand falling fastest. Earlier initiation might reduce early on-ART utilization rates. [ABSTRACT FROM AUTHOR]

Provides information on the impact of HIV and AIDS on social and economic development in Africa. Increase in the annual average medical cost for employees according to a study in Zambia; Issue concerning the pricing of anti-retroviral therapy for patients with HIV/AIDS; Significance of community involvement in reducing the spread of the infection.

Introduction: Secondary distribution of HIV self‐tests (HIVST) by HIV‐negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV). Methods: We conducted an open‐label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard‐of‐care (SOC; invitation letter to male partner for fast‐track testing). Women were followed until 12 months post‐partum. Male partners were offered confirmatory HIV testing and facilitated linkage to antiretroviral treatment (ART) or oral pre‐exposure prophylaxis (PrEP). Using intention‐to‐treat analysis, primary outcomes were male partner testing at the clinic and initiation on PrEP or ART evaluated through 12 months post‐partum (ClinicalTrials.gov, NCT03484533). Results: From November 2018 to March 2020, 500 PWLHIV were enrolled with a median age of 27 years (interquartile range [IQR] 23–30); 332 were randomized to HIVST and 168 to SOC with 437 PWLHIV (87.4%) completing 12 months follow‐up post‐partum. Of 236 male partners who tested at the clinic and enrolled (47.2%), their median age was 31 years (IQR 27–36), 45 (88.3%) men with HIV started ART and 113 (61.1%) HIV‐negative men started PrEP. There was no intervention effect on male partner testing (hazard ratio [HR] 1.04; 95% confidence interval [CI]: 0.79–1.37) or time to ART or PrEP initiation (HR 0.96; 95% CI: 0.69–1.33). Two male partners and two infants acquired HIV for an incidence of 0.99 per 100 person‐years (95% CI: 0.12–3.58) and 1.46 per 100 person‐years (95% CI: 0.18%–5.28%), respectively. Social harms related to study participation were experienced by six women (HIVST = 5, SOC = 1). Conclusions: Almost half of the partners of Ugandan PWLHIV tested for HIV with similar HIV testing rates and linkage to ART or PrEP among the secondary distribution of HIVST and SOC arms. Although half of men became aware of their HIV serostatus and linked to services, additional strategies to reach male partners of women in antenatal care are needed to increase HIV testing and linkage to services among men. [ABSTRACT FROM AUTHOR]

Kaposi sarcoma‐associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV‐immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18‐74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV‐1 and KSHV before and after ART rollout. We measured seropositivity to HIV‐1, KSHV latency‐associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case‐control‐adjusted odds ratios (ORadj) and 95% confidence intervals (CI) in relation to KS and KSHV infection, before (1995‐2004), early (2005‐2009) and late (2010‐2016) ART rollout periods. KSHV seropositivity among 1237 KS cases was 98%. Among 6649 controls, KSHV seropositivity was higher in males (ORadj = 1.4 [95%CI 1.23‐1.52]), in persons with HIV, (ORadj = 4.2 [95%CI 3.74‐4.73]) and lower in high school leavers (ORadj = 0.7 [95%CI 0.59‐0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28% and 28%, Ptrend <.001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend <.001). HIV‐1 seroprevalence increased from 10% in the pre‐ART period to 22% in the late ART period (Ptrend <.001). Compared to HIV‐1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI 11‐62) in HIV‐1 seronegative participants and an OR of 2501 (95%CI 1083‐5776) in HIV‐1 seropositive participants. HIV‐1 increases the risk of KS in those infected with KSHV by 100‐fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene. [ABSTRACT FROM AUTHOR]

Background. There are only a few comprehensive studies of adherence to ART and its challenges in Africa. This paper aims to assess the evidence on the challenges and prospects of ART adherence in sub-Saharan Africa. Methods. The authors reviewed original and review articles involving HIV-positive individuals that measured adherence to ART and its predictors in the past decade. Findings. Against expectations, sub-Saharan Africa patients have similar or higher adherence levels compared to those of developed countries. The challenges to ART adherence include factors related to patients and their families, socioeconomic factors, medication, and healthcare systems. Conclusion. Despite good adherence and program-related findings, antiretroviral treatment is challenged by a range of hierarchical and interrelated factors. There is substantial room for improvement of ART programs in sub-Sahara African countries. [ABSTRACT FROM AUTHOR]

The article comments on the paper "Intellectual property organizations and pharmaceutical patents in Africa," by Deiss Robert, published in a 2007 issue of the journal "Social Science and Medicine." The paper looks at the factors for the low number of patent applications for HIV antiretroviral drugs in African countries and the higher numbers of patents filed by countries which are members of two African intellectual property organizations.

The emergence of alternative medicines for AIDS in Asia and Africa was discussed at a satellite symposium and the parallel session on alternative and traditional treatments of the AIDSImpact meeting, held in Marseille, in July 2007. These medicines are heterogeneous, both in their presentation and in their geographic and cultural origin. The sessions focused on the role of these medications in selected resource poor settings in Africa and Asia now that access to anti-retroviral therapy is increasing. The aims of the sessions were to (1) identify the actors involved in the diffusion of these alternative medicines for HIV/AIDS, (2) explore uses and forms, and the way these medicines are given legitimacy, (3) reflect on underlying processes of globalisation and cultural differentiation, and (4) define priority questions for future research in this area. This article presents the insights generated at the meeting, illustrated with some findings from the case studies (Uganda, Senegal, Benin, Burkina Faso, China and Indonesia) that were presented. These case studies reveal the wide range of actors who are involved in the marketing and supply of alternative medicines. Regulatory mechanisms are weak. The efficacy claims of alternative medicines often reinforce a biomedical paradigm for HIV/AIDS, and fit with a healthy living ideology promoted by AIDS care programs and support groups. The AIDSImpact session concluded that more interdisciplinary research is needed on the experience of people living with HIV/AIDS with these alternative medicines, and on the ways in which these products interact (or not) with anti-retroviral therapy at pharmacological as well as psychosocial levels. [ABSTRACT FROM AUTHOR]

The spectrum of placental pathology in human immunodeficiency virus (HIV) is vast. Features observed are not only limited to the effects of the virus itself but may include that of coinfections such as tuberculosis and syphilis. The presence of other comorbidities and changes as a result of antiretroviral therapy may further confound the histologic findings. There is a paucity of unbiased information of the effects of maternal HIV on the placenta and how these changes relate to birth outcomes. Antiretroviral therapy, now in widespread use, has altered the course of maternal HIV disease and it is unknown whether this has altered the pathophysiology of HIV on the placenta. HIV-associated placental findings that have been most well described include acute chorioamnionitis, low placental weight, and maternal vascular malperfusion, with a tendency towards lower rates of chronic villitis. [ABSTRACT FROM AUTHOR]

Since 1999, many African governments have launched programs to offer short-course antiretroviral drug regimens to reduce mother-to child transmission of HIV. HIV testing in prenatal care is the gateway to these antiretroviral regimens. Pilot projects in Africa show an uptake of antiretroviral drugs in 8% to 50% of pregnant women presumed to be HIV infected; often, a minority of eligible women in care received these regimens. Use of lay counselors and rapid onsite HIV testing may alleviate health service barriers. Community education to promote voluntary counseling and testing, which involves men, is the long-term solution. In the short term, possibilities to enhance delivery of an effective intervention include group pretest counseling, universal offer of testing with women having the right to "opt out," universal treatment (mass treatment for those whose HIV status is not determined by voluntary counseling and testing), universal testing with women having the right to "opt out" of learning their test results, and mass treatment for all without testing. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials.Methods and Findings: We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children.Conclusions: Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis preventive therapy (TPT) reduces TB-related morbidity and mortality in people living with HIV (PLHIV). Cascade-of-care analyses help identify gaps and barriers in care and develop targeted solutions. A previous latent tuberculosis infection (LTBI) cascade-of-care analysis showed only 18% of persons in at-risk populations complete TPT, but a similar analysis for TPT among PLHIV has not been completed. We conducted a meta-analysis to provide this evidence.Methods and Findings: We first screened potential articles from a LTBI cascade-of-care systematic review published in 2016. From this study, we included cohorts that reported a minimum of 25 PLHIV. To identify new cohorts, we used a similar search strategy restricted to PLHIV. The search was conducted in Medline, Embase, Health Star, and LILACS, from January 2014 to February 2021. Two authors independently screened titles and full text and assessed risk of bias using the Newcastle-Ottawa Scale for cohorts and Cochrane Risk of Bias for cluster randomized trials. We meta-analyzed the proportion of PLHIV completing each step of the LTBI cascade-of-care and estimated the cumulative proportion retained. These results were stratified based on cascades-of-care that used or did not use LTBI testing to determine eligibility for TPT. We also performed a narrative synthesis of enablers and barriers of the cascade-of-care identified at different steps of the cascade. A total of 71 cohorts were included, and 70 were meta-analyzed, comprising 94,011 PLHIV. Among the PLHIV included, 35.3% (33,139/94,011) were from the Americas and 29.2% (27,460/94,011) from Africa. Overall, 49.9% (46,903/94,011) from low- and middle-income countries, median age was 38.0 [interquartile range (IQR) 34.0;43.6], and 65.9% (46,328/70,297) were men, 43.6% (29,629/67,947) were treated with antiretroviral therapy (ART), and the median CD4 count was 390 cell/mm3 (IQR 312;458). Among the cohorts that did not use LTBI tests, the cumulative proportion of PLHIV starting and completing TPT were 40.9% (95% CI: 39.3% to 42.7%) and 33.2% (95% CI: 31.6% to 34.9%). Among cohorts that used LTBI tests, the cumulative proportions of PLHIV starting and completing TPT were 60.4% (95% CI: 58.1% to 62.6%) and 41.9% (95% CI:39.6% to 44.2%), respectively. Completion of TPT was not significantly different in high- compared to low- and middle-income countries. Regardless of LTBI test use, substantial losses in the cascade-of-care occurred before treatment initiation. The integration of HIV and TB care was considered an enabler of the cascade-of-care in multiple cohorts. Key limitations of this systematic review are the observational nature of the included studies, potential selection bias in the population selection, only 14 cohorts reported all steps of the cascade-of-care, and barriers/facilitators were not systematically reported in all cohorts.Conclusions: Although substantial losses were seen in multiple stages of the cascade-of-care, the cumulative proportion of PLHIV completing TPT was higher than previously reported among other at-risk populations. The use of LTBI testing in PLHIV in low- and middle-income countries was associated with higher proportion of the cohorts initiating TPT and with similar rates of completion of TPT. [ABSTRACT FROM AUTHOR]

This multicountry prospective study investigated whether persistent systemic inflammation, measured by 8 plasma biomarkers, in HIV-1-infected Africans during suppressive antiretroviral therapy (ART) (viral load <50 copies/mL), was associated with CD4+ T-cell recovery and viral rebound (>1000 copies/mL) during long-term treatment. On-ART sCD14 and C-reactive protein concentrations were inversely associated with subsequent CD4+ T-cell counts. Risk of viral rebound was increased for participants with higher on-ART CXCL10 concentrations and reduced for those with a greater sCD163 decline during the first year of ART. Persistent systemic inflammation predicted CD4+ T-cell recovery and viral rebound, warranting further mechanistic research in relation to clinical outcomes. [ABSTRACT FROM AUTHOR]

Little is known about how CD4 and viral load testing have evolved following implementation of universal test and treat (UTT) in African settings. We reviewed World Health Organization (WHO) guidance from 2013 to 2018, and compared it against national HIV policies in Malawi, Tanzania and South Africa. Three surveys rounds were conducted in 2013, 2016 and 2017–2018 in 33 health facilities across the three settings to assess implementation of national policies on the use of biological markers. Qualitative interviews were conducted with 26 HIV policymakers or programme managers, 21 providers and 66 people living with HIV to explore understandings and experiences of these tests. Various factors influenced adoption and implementation of WHO guidance, including historical policies on CD4 counts, governance issues, supply chain challenges and funding mechanisms. Facility-level practices relating to the use of these tests often diverged from national policies. Patients and providers valued both tests, but did not always understand their roles. In addition to continued support for scaling-up viral load testing, renewed focus should be placed on the ongoing value of point-of-care CD4 tests in the UTT era, including its role in assessing disease progression and informing clinical management of cases to reduce HIV-related mortality. [ABSTRACT FROM AUTHOR]

Background: Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART.Methods: Consecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at  three months and one year of follow-up.Results: 468 patients with a median CD4 count of 59 cells/uL were enrolled. There were 140 patients (29.9%) with newly diagnosed TB in the first year of follow-up of which 79 (56.4%) were microbiologically-confirmed. A total of 18% (n = 84) required hospital admission and 12.2% (n = 57) died within a year of study entry. 38 out of 468 (8.1%) patients retrospectively tested urine-LAM positive - including 19.0% of those with microbiologically-proven TB diagnoses (n = 15/79) and 23.0% (n = 14/61) of those with clinical-only TB diagnoses; 9 of 38 (23.7%) of patients retrospectively testing LAM positive were never diagnosed with TB under routine program conditions. Among all patients (n = 468) in the first year of follow-up, a positive urine-LAM result was strongly associated with all-cause hospitalization and mortality with a corresponding adjusted hazard ratio (aHR) of 3.7 (95%CI, 1.9-7.1) and 2.6 (95%, 1.2-5.7), respectively.Conclusions: Systematic urine-LAM testing among ART-naïve HIV-positive outpatients with CD4 counts < 100 cells/uL detected TB cases that were missed under routine programme conditions and was highly predictive for subsequent hospitalization and mortality in the first year of ART. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus‐ (HIV‐) infection and antiretroviral therapy (ART) exposure are associated with bone loss. African data are limited despite the region's HIV burden. Of 247 ART‐naïve, premenopausal, urban, black African women aged 33.9 ± 6.6 years from Soweto, South Africa, measured at baseline, 110 underwent anthropometry, DXA, and blood and urine collections at 12 and 24 months; 39 were HIV‐negative (Nref), 28 were people with HIV (PWH) not ART‐exposed for the duration of the study (ART‐N), and 43 were PWH who were ART‐exposed within the first 12 months (ART‐Y). At baseline, the ART‐Y group had lower BMI and fat mass than the Nref group. Within 12 months of ART initiation, areal bone mineral density (aBMD) had decreased at the lumbar spine and at the whole body less head, despite increased weight, and hip aBMD had not increased in line with the Nref group. There was no evidence of further bone changes between 12 and 24 months. By 24 months, the ART‐Y women had gained weight and fat mass, but remained lighter with less fat than the Nref women. ART initiation normalized the low serum albumin of the ART‐Y group at baseline, but was associated with elevated bone turnover markers at 12 and 24 months. Vitamin D status and renal phosphate handling were normal. ART‐N had similar aBMD and other characteristics to the Nref group throughout, except unlike the Nref group, weight and fat mass did not increase and serum albumin decreased. This study in African women of childbearing age demonstrated that the bone loss that had occurred in these PWH after ART initiation did not continue after 12 months and that bone loss did not occur in ART‐unexposed PWH over 2 years. At 24 months, despite gains in weight and fat mass, ART‐exposed women remained lighter, with lower aBMD, fat mass, and higher bone turnover than women without HIV. More studies are required to establish if the bone loss and fat gain reverse, stabilize, or continue with further ART exposure, particularly during and after menopause. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objectives: We extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy. Methods: We propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain. Results: Through simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38–62 weeks versus 55–93 weeks in those receiving non-d4T-based regimens. Discussion: PS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves. [ABSTRACT FROM AUTHOR]

Objective: To estimate facility-level average cost for ART services and explore unit cost variations using pooled facility-level cost estimates from four HIV empirical cost studies conducted in five African countries. Methods: Through a literature search we identified studies reporting facility-level costs for ART programmes. We requested the underlying data and standardised the disparate data sources to make them comparable. Subsequently, we estimated the annual cost per patient served and assessed the cost variation among facilities and other service delivery characteristics using descriptive statistics and meta-analysis. All costs were converted to 2017 US dollars ($). Results: We obtained and standardised data from four studies across five African countries and 139 facilities. The weighted average cost per patient on ART was $251 (95% CI: 193–308). On average, 46% of the mean unit cost correspond to antiretroviral (ARVs) costs, 31% to personnel costs, 20% other recurrent costs, and 2% to capital costs. We observed a lot of variation in unit cost and scale levels between countries. We also observed a negative relationship between ART unit cost and the number of patients served in a year. Conclusion: Our approach allowed us to explore unit cost variation across contexts by pooling ART costs from multiple sources. Our research provides an example of how to estimate costs based on heterogeneous sources reconciling methodological differences across studies and contributes by giving an example on how to estimate costs based on heterogeneous sources of data. Also, our study provides additional information on costs for funders, policy-makers, and decision-makers in the process of designing or scaling-up HIV interventions. [ABSTRACT FROM AUTHOR]

Background: Research emphasizes lasting psychological implications when young people are not adequately supported following close family deaths. In sub-Saharan Africa, adolescents living with HIV (ALHIV) experience multiple personal deaths along with other serious losses. ALHIV highlight that not processing their grief negatively impacts their daily lives including their ART adherence. This article describes the development and piloting of a bereavement intervention for ALHIV in Zimbabwe. Methods: Formative research with 10 ALHIV peer counsellors (18–21 years) supported intervention development. After training, these peer counsellors facilitated a six-session bereavement intervention in 10 existing community-based ALHIV support groups. Qualitative data was collected from facilitators, ALHIV intervention participants, and their caregivers. Results: Key themes: i) limited experience recognizing their losses; ii) lacking control over poorly understood feelings; iii) recurrent feelings of isolation, hopelessness, depression, fear, and guilt; iv) reticence to share, believing their feelings were unusual; v) shame surrounding connections felt towards their deceased. Following intervention implementation, members reported relief in learning of shared experiences, the ability to link their feelings with specific experiences and employ constructive coping strategies to address them, leading to greater emotional control. Conclusion: Implementing high-quality grief interventions is critical when responding to the complex realities of ALHIV in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Adherence to antiretroviral therapy (ART) and long-term uninterrupted engagement in HIV care is difficult for HIV-positive people, and randomized trials of specific techniques to promote adherence often show small or negligible effects. Understanding what influences decision-making in HIV-positive people in Africa may help researchers and policy makers in the development of broader, more effective interventions and policies. Methods: We used thematic synthesis and a grounded theory approach to generate a detailed narrative and theoretical model reflecting life with HIV in Africa, and how this influences ART adherence and engagement decisions. We included qualitative primary studies that explored perspectives, perceptions and experiences of HIV-positive people, caregivers and healthcare service providers. We searched databases from 1 January 2013 to 9 December 2016, screened all studies, and selected those for inclusion using purposeful sampling methods. Included studies were coded with Atlas.ti, and we assessed methodological quality across five domains. Results: We included 59 studies from Africa in the synthesis. Nine themes emerged which we grouped under three main headings. First, people who are HIV-positive live in a complicated world where they must navigate the challenges presented by poverty, competing priorities, unpredictable life events, social identity, gender norms, stigma, and medical pluralism—these influences can make initiating and maintaining ART difficult. Second, the health system is generally seen as punishing and uninviting and this can drive HIV-positive people out of care. Third, long-term engagement and adherence requires adaptation and incorporation of ART into daily life, a process which is facilitated by: inherent self-efficacy, social responsibilities, previous HIV-related illnesses and emotional, practical or financial support. These factors together can lead to a “tipping point”, a point in time when patients choose to either engage or disengage from care. HIV-positive people may cycle in and out of these care states in response to fluctuations in influences over time. Conclusion: This analysis provides a practical theory, arising from thematic synthesis of research, to help understand the dynamics of adherence to ART and engagement in HIV care. This can contribute to the design of service delivery approaches, and informed thinking and action on the part of policy makers, providers, and society: to understand what it is to be HIV-positive in Africa and how attitudes and the health service need to shift to help those with HIV lead ‘normal’ lives. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus (HIV)-infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on ART may improve survival, although this has not been reliably quantified. Methods. Individual data on 19 219 HEU children from 21 PMTCT trials/cohorts undertaken from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" were used to estimate the relative contribution of risk factors to overall mortality. Results. Cumulative incidence of death was 5.5% (95% confidence interval, 5.1-5.9) by age 24 months. Low birth weight (LBW <2500 g, adjusted hazard ratio (aHR, 2.9), no breastfeeding (aHR, 2.5), and maternal death (aHR, 11.1) were significantly associated with increased mortality. Maternal ART (aHR, 0.5) was significantly associated with lower mortality. At the population level, LBW accounted for 16.2% of 24-month mortality, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; combined, these factors explained 63.6% of deaths by age 24 months. Conclusions. Survival of HEU children could be substantially improved if public health practices provided all HIV-infected mothers with ART and supported optimal infant feeding and care for LBW neonates. [ABSTRACT FROM AUTHOR]

Introduction: HIV-1 polymerase chain reaction (PCR) testing at birth aims to facilitate earlier initiation of antiretroviral therapy (ART) for HIV-infected neonates. Data from two years of universal birth testing implementation in a high-burden South African urban setting are presented to demonstrate the prevalence and outcomes of diagnostic challenges in this context. Methods: HIV-exposed neonates born at Rahima Moosa Mother and Child Hospital between 5 June 2014 and 31 August 2016 were routinely screened at birth for HIV-1 on whole blood samples using the COBAS® AmpliPrep/COBAS® TaqMan (CAP/CTM) HIV-1 Qualitative Test, version 2.0 (Roche Molecular Systems, Inc., Branchburg, NJ, USA). Virological results were interpreted according to standard operating procedures with the South African National Health Laboratory Service. All neonates with non-negative results were actively followed-up and categorized according to HIV infection status as positive, negative, uncertain and lost to follow-up (LTFU). Results: 104 (1.8%) of 5743 HIV-exposed neonates received a non-negative birth PCR result, for which laboratory data were available for 102 (98%) cases - 78 (76%) tested positive and 24 (24%) indeterminate. HIV infection status was confirmed positive in 83 (81%) infants, negative in 8 (8%), uncertain in 5 (5%) and LTFU in 6 (6%) cases. The positive predictive value (excluding cases of uncertain diagnosis and inadequate testing) following a non-negative HIV-1 PCR screening test at birth was 0.91 (83/91; 95% confidence interval: 0.85-0.96). Neonates testing positive at birth had significantly higher viral load (VL) results than those testing indeterminate at birth of 4.5 and 3.0 log copies/ml ( p = 0.0007), respectively. Similarly, mothers of neonates with positive as compared to indeterminate birth test results had higher VLs of 4.5 and 2.7 log copies/ml ( p = 0.0013), respectively. Half of neonates with an indeterminate birth test were shown to be HIV-infected on subsequent confirmatory testing, with time to final diagnosis 30 days longer for these neonates ( p < 0.0001). Conclusion: Indeterminate HIV-1 PCR results accounted for a quarter of non-negative results at birth and were associated with a high risk of infection in comparison to the risk of in utero transmission. Indeterminate birth results with positive HIV PCR results on repeat testing were associated with later final diagnosis. The HIV-1 status remains uncertain in a minority of cases because of repeatedly indeterminate results, highlighting the need for more sensitive and specific virological tests. [ABSTRACT FROM AUTHOR]

Introduction: Increasingly, there is a need for health authority scale up of successfully piloted differentiated models of antiretroviral therapy (ART) delivery. However, there is a paucity of evidence on system-wide outcomes after scale-up. In the Cape Town health district, stable adult patients were referred to adherence clubs (ACs) - a group model of ART delivery with five visits per year. By the end of March 2015, over 32,000 ART patients were in an AC. We describe patient outcomes of a representative sample of AC patients during this scale-up. Methods: Patients enrolled in an AC at non-research supported sites between 2011 and 2014 were eligible for analysis. We sampled 10% of ACs ( n = 100) in quintets proportional to the number of ACs at each facility, linking each patient to city-wide laboratory and service access data to validate retention and virologic outcomes. We digitized registers and used competing risks regression and cross-sectional methods to estimate outcomes: mortality, transfers, loss to follow-up (LTFU) and viral load suppression (≤400 copies/mL). Predictors of LTFU and viral rebound were assessed using Cox proportional hazards models. Results: Of the 3216 adults contributing 4019 person years of follow-up (89% in an AC, median 1.1 years), 70% were women. Retention was 95.2% (95% CI, 94.0-96.4) at 12 months and 89.3% (95% CI, 87.1-91.4) at 24 months after AC enrolment. In the 13 months prior to analysis closure, 88.1% of patients had viral load assessments and of those, viral loads ≤400 copies/mL were found in 97.2% (95% CI, 96.5-97.8) of patients. Risk of LTFU was higher in younger patients and in patients accessing ART from facilities with larger ART cohorts. Risk of viral rebound was higher in younger patients, those that had been on ART for longer and patients that had never sent a buddy to collect their medication. Conclusions: This is the first analysis reporting patient outcomes after health authorities scaled-up a differentiated care model across a high burden district. The findings provide substantial reassurance that stable patients on long-term ART can safely be offered care options, which are more convenient to patients and less burdensome to services. [ABSTRACT FROM AUTHOR]

The second Medicines Utilization Research in Africa (MURIA) group workshop and symposium again brought researchers together from across Africa to improve their knowledge of drug utilization (DU) methodologies and exchange ideas to further progress DU research in Africa. This built on extensive activities from the first conference including workshops and multiple publications. Anti-infectives were again the principal theme for the 2016 symposium following the workshops. This included presentations regarding strategies to improve antibiotic utilization among African countries, such as point-prevalence studies, as well as potential ways to reduce self-purchasing of antibiotics. There were also presentations on antiretrovirals including renal function and the impact of policy changes. Concerns with adherence in chronic treatments as well as drug-drug interactions and their implications were also discussed. The deliberations resulted in a number of agreed activities including joint publications before the next MURIA conference in Namibia in 2017. [ABSTRACT FROM PUBLISHER]

Background: Lablite is an implementation project supporting and studying decentralized antiretroviral therapy (ART) rollout to rural communities in Malawi, Uganda and Zimbabwe. Task shifting is one of the strategies to deal with shortage of health care workers (HCWs) in ART provision. Evaluating Human Resources for Health (HRH) optimization is essential for ensuring access to ART. The Lablite project started with a baseline survey whose aim was to describe and compare national and intercountry delivery of ART services including training, use of laboratories and clinical care. Methods: A cross-sectional survey was conducted between October 2011 and August 2012 in a sample of 81 health facilities representing different regions, facility levels and experience of ART provision in Malawi, Uganda and Zimbabwe. Using a questionnaire, data were collected on facility characteristics, human resources and service provision. Thirty three (33) focus group discussions were conducted with HCWs in a subset of facilities in Malawi and Zimbabwe. Results: The survey results showed that in Malawi and Uganda, primary care facilities were run by non-physician clinical officers/medical assistants while in Zimbabwe, they were run by nurses/midwives. Across the three countries, turnover of staff was high especially among nurses. Between 10 and 20% of the facilities had at least one clinical officer/medical assistant leave in the 3 months prior to the study. Qualitative results show that HCWs in ART and non-ART facilities perceived a shortage of staff for all services, even prior to the introduction of ART provision. HCWs perceived the introduction of ART as having increased workload. In Malawi, the number of people on ART and hence the workload for HCWs has further increased following the introduction of Option B+ (ART initiation and life-long treatment for HIV positive pregnant and lactating women), resulting in extended working times and concerns that the quality of services have been affected. For some HCWs, perceived low salaries, extended working schedules, lack of training opportunities and inadequate infrastructure for service provision were linked to low job satisfaction and motivation. Conclusions: ART has been decentralized to lower level facilities in the context of an ongoing HRH crisis and staff shortage, which may compromise the provision of high-quality ART services. Task shifting interventions need adequate resources, relevant training opportunities, and innovative strategies to optimize the operationalization of new WHO treatment guidelines which continue to expand the number of people eligible for ART. [ABSTRACT FROM AUTHOR]

Background:  Diagnosis of human immunodeficiency virus (HIV) infection during early infancy (commonly known as "early infant HIV diagnosis" [EID]) followed by prompt initiation of antiretroviral therapy dramatically reduces mortality. EID testing is recommended at 6 weeks of age, but many infant infections are missed.Design/methods:  We simulated 4 EID testing strategies for HIV-exposed infants in South Africa: no EID (diagnosis only after illness; hereafter, "no EID"), testing once (at birth alone or at 6 weeks of age alone; hereafter, "birth alone" and "6 weeks alone," respectively), and testing twice (at birth and 6 weeks of age; hereafter "birth and 6 weeks"). We calculated incremental cost-effectiveness ratios (ICERs), using discounted costs and life expectancies for all HIV-exposed (infected and uninfected) infants.Results:  In the base case (guideline-concordant care), the no EID strategy produced a life expectancy of 21.1 years (in the HIV-infected group) and 61.1 years (in the HIV-exposed group); lifetime cost averaged $1430/HIV-exposed infant. The birth and 6 weeks strategy maximized life expectancy (26.5 years in the HIV-infected group and 61.4 years in the HIV-exposed group), costing $1840/infant tested. The ICER of the 6 weeks alone strategy versus the no EID strategy was $1250/year of life saved (19% of South Africa's per capita gross domestic product); the ICER for the birth and 6 weeks strategy versus the 6 weeks alone strategy was $2900/year of life saved (45% of South Africa's per capita gross domestic product). Increasing the proportion of caregivers who receive test results and the linkage of HIV-positive infants to antiretroviral therapy with the 6 weeks alone strategy improved survival more than adding a second test.Conclusions:  EID at birth and 6 weeks improves outcomes and is cost-effective, compared with EID at 6 weeks alone. If scale-up costs are comparable, programs should add birth testing after strengthening 6-week testing programs. [ABSTRACT FROM AUTHOR]

Background: Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce.Methods: This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa.Results: Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001). The prevalence of depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001). Both alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77) and alcohol use disorder (2.73, 95 % CI: 1.68-4.42) were significantly associated with poor adherence. There was, however, no significant association with viral suppression.Conclusions: Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression.Trial Registration: April 28th 2014; NCT02126696 . [ABSTRACT FROM AUTHOR]

Despite improved availability of simple, relatively inexpensive, and highly effective antiretroviral treatment for HIV/AIDS, the disease remains a major public health challenge for women in sub-Saharan Africa (SSA). Given the numerous barriers in access to care for women in this region, every health issue that brings them into contact with the health system should be optimized as an opportunity to integrate HIV/AIDS prevention. Because most non-condom forms of modern contraception require a clinical appointment for use, contraception appointments could provide a confidential opportunity for access to HIV counseling, testing, and referral to care. This study sought to investigate the relationship between contraceptive methods and HIV testing among women in SSA. Data from the Demographic and Health Survey from four African countries—Congo, Mozambique, Nigeria, and Uganda—was used to examine whether modern (e.g., pills, condom) or traditional (e.g., periodic abstinence, withdrawal) forms of contraception were associated with uptake of HIV testing. Data for the current analyses were restricted to 35,748 women with complete information on the variables of interest. Chi-square tests and logistic regression models were used to assess the relationship between uptake of HIV testing and respondents' baseline characteristics and contraceptive methods. In the total sample and in Mozambique, women who used modern forms of contraception were more likely to be tested for HIV compared to those who did not use contraception. This positive association was not demonstrated in Congo, Nigeria, or Uganda. That many women who access modern contraception are not tested for HIV in high HIV burden areas highlights a missed opportunity to deliver an important intervention to promote maternal and child health. Given the increasing popularity of hormonal contraception methods in low-income countries, there is an urgent need to integrate HIV counseling, testing, and treatment into family planning programs. Women on hormonal contraceptives should be encouraged to continue to use condoms for HIV-prevention. [ABSTRACT FROM AUTHOR]

Background: Decentralization of ART services scaled up significantly with the country wide roll out of option B plus in Uganda. Little work has been undertaken to examine population level access to HIV care particularly in hard to reach areas in rural Africa. Most work on ART scale up has been done at health facility level which omits people not accessing healthcare in the community. This study describes health service usage, particularly HIV testing and care in 2/6 parishes of Lapono sub-county of northern Uganda, prior to introduction of ART services in Lira Kato Health Centre (a local lower-level health centre III), as part of ART decentralization.Methods: Household and individual questionnaires were administered to household members (aged 15-59 years). Logit random effects models were used to test for differences in proportions (allowing for clustering within villages).Results: 2124 adults from 1351 households were interviewed (755 [36%] males, 1369 [64 %] females). 2051 (97%) participants reported seeking care locally for fever, most on foot and over half at Lira Kato Health Centre. 574 (76%) men and 1156 (84%) women reported ever-testing for HIV (P < 0.001 for difference); 34/574 (6%) men and 102/1156 (9%) women reported testing positive (P = 0.04). 818/850 (96%) women who had given birth in the last 5 years had attended antenatal care in their last pregnancy: 7 women were already diagnosed with HIV (3 on ART) and 790 (97%) reported being tested for HIV (34 tested newly positive). 124/136 (91%) HIV-positive adults were in HIV-care, 123/136 (90 %) were taking cotrimoxazole and 74/136 (54%) were on ART. Of adults in HIV-care, most were seen at Kalongo hospital (n = 87), Patongo Health Centre (n = 7) or Lira Kato Health Centre (n = 23; no ART services). 58/87, 5/7 and 20/23 individuals walked to Kalongo hospital (56 km round-trip, District Health Office information), Patongo Health Centre (76 km round-trip, District Health Office information) and Lira Kato Health Centre (local) respectively. 8 HIV-infected children were reported; only 2 were diagnosed aged <24 months: 7/8 were in HIV-care including 3 on ART.Conclusions: Higher proportions of women compared to men reported ever-testing for HIV and testing HIV-positive, similar to other surveys. HIV-infected men and women travelled considerable distances for ART services. Children appeared to be under-accessing testing and referral for treatment. Decentralization of ART services to a local health facility would decrease travel time and transport costs, making care and treatment more easily accessible. [ABSTRACT FROM AUTHOR]

Background: Across sub-Saharan Africa, men's levels of HIV-testing remain inadequate relative to women's. Men are less likely to access anti-retroviral therapy and experience higher levels of morbidity and mortality once initiated on treatment. More frequent HIV-testing by men at continued risk of HIV-infection is required to facilitate earlier diagnosis. This study explored the frequency of HIV-testing among a rural population of men and the factors associated with more frequent HIV-testing.Methods: We conducted a secondary analysis of a population-based survey in three rural district in Zambia, from February-November, 2013. Households (N = 300) in randomly selected squares from 42 study sites, defined as a health facility and its catchment area, were invited to participate. Individuals in eligible households were invited to complete questionnaires regarding demographics and HIV-testing behaviours. Men were defined as multiple HIV-testers if they reported more than one lifetime test. Upon questionnaire completion, individuals were offered rapid home-based HIV-testing.Results: Of the 2376 men, more than half (61%) reported having ever-tested for HIV. The median number of lifetime tests was 2 (interquartile range = 1-3). Just over half (n = 834; 57%) of ever-testers were defined as multiple-testers. Relative to never-testers, multiple-testers had higher levels of education and were more likely to report an occupation. Among the 719 men linked to a spouse, multiple-testing was higher among men whose spouse reported ever-testing (adjusted prevalence ratio = 3.02 95% CI: 1.37-4.66). Multiple-testing was higher in study sites where anti-retroviral therapy was available at the health facility on the day of a health facility audit. Among ever-testers, education and occupation were positively associated with multiple-testing relative to reporting one lifetime HIV-test. Almost half (49%) of ever-testers accepted the offer of home-based HIV-testing.Discussion: Reported HIV-testing increased among this population of men since a 2011/12 survey. Yet, only 35% of all men reported multiple lifetime HIV-tests. The factors associated with multiple HIV-testing were similar to factors associated with ever-testing for HIV. Men living with HIV were less likely to report multiple HIV-tests and employment and education were associated with multiple-testing. The offer of home-based HIV-testing increased the frequency of HIV-testing among men.Conclusion: Although men's levels of ever-testing for HIV have increased, strategies need to increase the lifetime frequency of HIV-testing among men at continued risk of HIV-infection. [ABSTRACT FROM AUTHOR]

We examined differences in HIV-infected U.S.-born and foreign-born black mothers who delivered perinatally HIV-exposed and -infected children during 1995-2004 in the Pediatric Spectrum of HIV Disease Project, a longitudinal cohort study. Prevalence ratios were calculated to explain differences in perinatal HIV prevention opportunities comparing U.S.-born to foreign-born and African-born to Caribbean-born black mothers. U.S.-born compared with foreign-born HIV-infected black mothers were significantly more likely to have used cocaine or other non-intravenous illicit drugs, exchanged money or drugs for sex, known their HIV status before giving birth, received intrapartum antiretroviral (ARV) prophylaxis, and delivered a premature infant; and were significantly less likely to have received prenatal care or delivered an HIV-infected infant. African-born compared with Caribbean-born black mothers were more likely to receive intrapartum ARV prophylaxis. These differences by maternal geographical origin have important implications for perinatal HIV transmission prevention, and highlight the validity of disaggregating data by racial/ethnic subgroups. [ABSTRACT FROM AUTHOR]

Introduction: HIV incidence remains high among young women in sub-Saharan Africa in spite of scale-up of HIV testing, behavioural interventions, antiretroviral treatment and medical male circumcision. There is a critical need to critique past approaches and learn about the most effective implementation of evidence-based HIV prevention strategies, particularly emerging interventions such as pre-exposure prophylaxis (PrEP). Discussion: Women in sub-Saharan Africa are at increased risk of HIV during adolescence and into their 20s, in part due to contextual factors including gender norms and relationship dynamics, and limited access to reproductive and sexual health services. We reviewed behavioural, behavioural economic and biomedical approaches to HIV prevention for young African women, with a particular focus on the barriers, opportunities and implications for implementing PrEP in this group. Behavioural interventions have had limited impact in part due to not effectively addressing the context, broader sexual norms and expectations, and structural factors that increase risk and vulnerability. Of biomedical HIV prevention strategies that have been tested, daily oral PrEP has the greatest evidence for protection, although adherence was low in two placebo-controlled trials in young African women. Given high efficacy and effectiveness in other populations, demonstration projects of open-label PrEP in young African women are needed to determine the most effective delivery models and whether women at substantial risk are motivated and able to use oral PrEP with sufficient adherence to achieve HIV prevention benefits. Conclusions: Social marketing, adherence support and behavioural economic interventions should be evaluated as part of PrEP demonstration projects among young African women in terms of their effectiveness in increasing demand and optimizing uptake and effective use of PrEP. Lessons learned through evaluations of implementation strategies for delivering oral PrEP, a firstgeneration biomedical HIV prevention product, will inform development of new and less user-dependent PrEP formulations and delivery of an expanding choice of prevention options in HIV prevention programmes for young African women. [ABSTRACT FROM AUTHOR]

Until recently, consensus existed in certain circles that the African industry was not suitable for cost-effective production of quality, safe drugs. Yet, public and private pharmaceutical enterprises have cropped up on the continent, with some venturing into production of sophisticated and complex drugs, such as antiretrovirals (ARVs). In our study, we analyse and contrast the dynamics of local pharmaceutical manufacturing in Mozambique and Zimbabwe with the objective of understanding why pharmaceutical production in Africa is picking up momentum and the influence of global funding for ARVs in this process. Our analysis identifies two routes of development for local pharmaceutical manufacturing: a favourable economic outlook and support from the international community created the necessary conditions for the development of the nascent pharmaceutical industry in Mozambique, while in Zimbabwe, the presence of an established local industry was instrumental in bringing in favourable, if not always coherent, government regulation. In both countries, the introduction of AIDS treatment created windows of opportunity for local production of pharmaceuticals by increasing public sector demand, providing fresh funds, and providing a justification for government regulation favouring local production. Despite the long-standing and well-known problems that created persistent shortcomings in human resources and in the economic and industrial environments, we conclude that pre-existing developmental roots, international funds and supportive state industrial policies are encouraging more manufacturers to enter the business of local pharmaceutical production in Africa. However, the opportunities brought in by fresh AIDS funds will need to be sensibly managed at both the local and global levels, as the world's interest on the disease may not last in the long term. [ABSTRACT FROM AUTHOR]

In Israel, antiretroviral therapy (ART) is available (at local pharmacies) without cost. Nevertheless, poor adherence, especially of immigrants from Africa, leads to a high rate of treatment failures. Our study looked whether direct monthly ART supply in our AIDS centre has an effect on adherence and outcome. A total of 385 HIV (clade C) immigrants from Africa that were treated with ART for >2 years prior to the initiation of the study were evaluated. During the first 2 years, ART medications were supplied by local pharmacies. Thereafter (next 2 years), all patients received medications, monthly at our centre. Adherence, immunological (CD4) and virological (VL) outcome at the end of the two study periods were determined. At baseline, only 75% of the patients attended more than 90% of scheduled visits with 57% treatment adherence. Virological failure (VL >40 copies/ml) was observed in 53% of the patients. As a result of our intervention (2 years of direct monthly ART supply), visits and treatment adherence significantly increased (90% and 84%, respectively; p < 0.001). Concomitantly, virological failure rate significantly dropped to 28% (p < 0.001). Direct monthly supply of ART is a relatively low-cost mode to improve patient's adherence and immunological/virological outcomes. [ABSTRACT FROM PUBLISHER]

Transforming repressive institutions into respected instruments of justice is necessary for the social reconstruction of fragile and postconflict states. Yet, little attention has been given to the role of health systems in facilitating such change. We situate South Africa’s right to access health care as part of a broader sociopolitical endeavour to ‘bring justice’ in the aftermath of apartheid and argue that street-level bureaucrats tasked with delivering health services are a gauge of both individual and institutional transformation. Using cases from two urban areas, we consider responses to inaccessible antiretroviral therapy, tuberculosis treatment and maternal deliveries and ask whether these ameliorate or compound access barriers. We also explore some conditions for bringing justice to street-level interactions. Our cases suggest that, if left unchallenged, negative street-level bureaucracy may compound inaccessible care for patients and perpetuate a wider culture of disempowerment, deprivation and poverty – ongoing structural violence – for citizens, while positive provider practices may be ameliorative. Strengthening street-level accountability and engendering respectful, empathetic provider practices is consequently vital to improving access to services and contributing more generally to the restoration of justice and health in society. [ABSTRACT FROM PUBLISHER]

Background Up to 40% of HIV-infected individuals receiving Highly Active Antiretroviral Therapy (HAART) have poor CD4+ T-cell recovery. The role of natural killer (NK) cells in immune recovery during HAART is not well understood. We described the profiles of NK cell subsets and their expression of activating receptor, NKG2D and cytotoxicity receptor NKp46 among suboptimal immune responders to despite four years of suppressive HAART. Methods A case control study utilized frozen peripheral blood mononuclear cells (PBMC) from a cohort of HIV-infected adults that initiated HAART in 2004/5, at CD4 < 200 cells/μl. Cases were 'suboptimal' responders; patients within the lowest quartile of CD4+ T-cell reconstitution, with a median CD4 count increase of 129 (-43-199) cells/μl (between baseline and after 4 years of HAART) and controls were 'super-optimal' responders; patients within the highest quartile of CD4 T-cell reconstitution with a median CD4 count increase of 528 (416-878) cells/μl). Expression of NK cell lineage markers (CD56+/-CD16+/-) and receptors NKG2D and NKp46, was measured among PBMC from 29 cases of 'suboptimal' responders' and 23 controls of 'super-optimal responders', and compared among 'suboptimal' and 'superoptimal' responders. NK cell populations were compared using the Holm Sidak multiple comparison test and p values < 0.05 were considered statistically significant. Data was analyzed using FLOWJO and GraphPad Prism 6. Results 'Suboptimal responders' had a higher proportion of cytokine producing CD56++CD16+/- (CD56bri) NK cells than the 'super-optimal responders' p = 0.017, and CD56neg NK cells were lower among suboptimal than super-optimal responders (p = 0.007). The largest NK cell subset, CD56dim, was comparable among suboptimal responders and 'super-optimal immune responders'. Expression of NKG2D and NKp46 receptors on NK cell subsets (CD56bri, CD56neg and CD56dim), was comparable among 'suboptimal' and 'super-optimal' immune responders. Conclusions The pro-inflammatory CD56++CD16-- NK cells were higher among 'suboptimal' responders relative to 'super-optimal' responders, despite four years of suppressive HAART. Alteration of NK cell populations could inhibit host immune responses to infections among suboptimal responders. We recommend further analysis of NK cell function among suboptimal immune responders in order to inform targeted interventions to optimize immune recovery among HAART-treated adults. [ABSTRACT FROM AUTHOR]

Background: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. Objective: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. Design: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. Results: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. Conclusions: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS. [ABSTRACT FROM AUTHOR]

Background: Substantial falls in the mortality of people living with HIV (PLWH) have been observed since the introduction of antiretroviral therapy (ART) in sub-Saharan Africa. However, access and uptake of ART have been variable in many countries.We report the excess deaths observed in PLWH before and after the introduction of ART. We use data from five longitudinal studies in Malawi, South Africa, Tanzania, and Uganda, members of the network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA). Methods: Individual data from five demographic surveillance sites that conduct HIV testing were used to estimate mortality attributable to HIV, calculated as the difference between the mortality rates in PLWH and HIV-negative people. Excess deaths in PLWH were standardized for age and sex differences and summarized over periods before and after ART became generally available. An exponential regression model was used to explore differences in the impact of ART over the different sites. Results: 127,585 adults across the five sites contributed a total of 487,242 person years. Before the introduction of ART, HIV-attributable mortality ranged from 45 to 88 deaths per 1,000 person years. Following ART availability, this reduced to 14-46 deaths per 1,000 person years. Exponential regression modeling showed a reduction of more than 50% (HR-0.43, 95% CI: 0.32-0.58), compared to the period before ART was available, in mortality at ages 15-54 across all five sites. Discussion: Excess mortality in adults living with HIV has reduced by over 50% in five communities in sub-Saharan Africa since the advent of ART. However, mortality rates in adults living with HIV are still 10 times higher than in HIV-negative people, indicating that substantial improvements can be made to reduce mortality further. This analysis shows differences in the impact across the sites, and contrasts with developed countries where mortality among PLWH on ART can be similar to that of the general population. Further research is urgently needed to establish why the different impacts on mortality were observed and how the care and treatment programmes in these countries can be more effective in reducing mortality further. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) estimates that only 30% of eligible, HIV-infected individuals start antiretroviral therapy (ART). This study seeks to explore the geographic and individual factors associated with starting ART on time. This retrospective study includes 15,734 HIV-positive adults initiating ART at two HIV clinics in Lilongwe, Malawi. The outcome was starting ART within two weeks of meeting ART eligibility as defined by the Malawi ART guidelines. Euclidean distance from patient neighbourhood to their clinic was calculated using Google Earth. Logistic regression models assessed factors influencing starting ART on time. Of 15,734 adults initiating ART, 8178 were from Lighthouse (LH) and 7556 were from Martin Preuss Center (MPC). Combined, 68.7% started treatment on time. Patients who were eligible for ART based on a CD4 cell count <250 cells/mm³ versus WHO stage were less likely to begin ART on time at both LH (odds ratio [OR] 0.16; 95% Cl 0.1 3-0.1 9) and MPC (OR 0.24; 95% Cl 0.21 -0.28). Likelihood of starting on time decreased with each kilometer further from clinic location among LH patients (OR 0.97; 95% Cl 0.94-0.99); distance was not significant at MPC. In conclusion, predictors differed by clinic. Distance to clinic and type of eligibility for ART significantly influence starting ART on time. [ABSTRACT FROM AUTHOR]

ABSTRACT Global health interventions to provide antiretroviral (ARV) drug treatment for people living with HIV/AIDS in developing countries have linked global and local actors in unprecedented ways. These uneven relationships have been described as creating new forms of citizenship that challenge the liberal understanding of rights and responsibilities bestowed by the state. A comparative case study based on fieldwork from South Africa and Uganda suggests different theoretical understandings of the link between technologies of AIDS treatment and relationships of belonging. Yet, ethnographic data from local clinics in both countries point to similarities that exist across AIDS interventions, and to the importance of counsellors in negotiating the rules of ARVs. Neither patients living with HIV nor the local providers of their AIDS treatment are 'bare life' subjects to be acted upon by a global development intervention. As ARV technologies are increasingly prescribed in developing country clinics, diverse social relationships are taught and negotiated as part of the pedagogy of biopolitics. The following discussion demonstrates how local counsellors and clients negotiate the rules of AIDS treatment together for mutual benefit. The article concludes that AIDS treatment creates relationships of therapeutic citizenship and clientship in ways that constrain the possibilities of citizenship and development. [ABSTRACT FROM AUTHOR]

Background: Behavioral interventions that promote adherence to antiretroviral medications may decrease HIV treatment failure. Antiretroviral treatment programs in sub-Saharan Africa confront increasing financial constraints to provide comprehensive HIV care, which include adherence interventions. This study compared the impact of counseling and use of an alarm device on adherence and biological outcomes in a resource-limited setting. Methods and Findings: A randomized controlled, factorial designed trial was conducted in Nairobi, Kenya. Antiretroviralnaı ¨ve individuals initiating free highly active antiretroviral therapy (HAART) in the form of fixed-dose combination pills (d4T,3TC, and nevirapine) were randomized to one of four arms: counseling (three counseling sessions around HAART initiation), alarm (pocket electronic pill reminder carried for 6 months), counseling plus alarm, and neither counseling nor alarm. Participants were followed for 18 months after HAART initiation. Primary study endpoints included plasma HIV-1 RNA and CD4 count every 6 months, mortality, and adherence measured by monthly pill count. Between May 2006 and September 2008, 400 individuals were enrolled, 362 initiated HAART, and 310 completed follow-up. Participants who received counseling were 29% less likely to have monthly adherence ,80% (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.49–1.01; p=0.055) and 59% lesslikely to experience viral failure (HIV-1 RNA $5,000 copies/ml) (HR 0.41; 95% CI 0.21–0.81; p=0.01) compared to those who received no counseling. There was no significant impact of using an alarm on poor adherence (HR 0.93; 95% CI 0.65–1.32; p=0.7) or viral failure (HR 0.99; 95% CI 0.53–1.84; p=1.0) compared to those who did not use an alarm. Neither counseling nor alarm was significantly associated with mortality or rate of immune reconstitution. Conclusions: Intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure during 18-month follow-up, while use of an alarm device had no effect. As antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counseling should be implemented to decrease the development of treatment failure and spread of resistant HIV. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Clinical outcomes of HIV-infected children on antiretroviral treatment (ART) in a decentralised, nurse/counsellor-led programme. DESIGN: Clinical cohort. SETTING: KwaZulu-Natal, South Africa. PATIENTS: HIV-infected children aged ≤15 years on ART, June 2004–2008. MAIN OUTCOME MEASURES: Survival according to baseline characteristics including age, WHO clinical stage, haemoglobin and CD4%, was assessed in Kaplan–Meier analyses. Hazard ratios for mortality were estimated using Cox proportional hazards regression and changes in laboratory parameters and weight-for-age z scores after 6–12 months' treatment were calculated. RESULTS: 477 HIV-infected children began ART at a median age of 74 months (range 4–180), median CD4 count (CD4%) of 433 cells/mm3(17%) and median HIV viral load of log 4.2 copies/ml; 105 (22%) were on treatment for tuberculosis and 317 (76.6%) were WHO stage 3/4. There were significant increases after ART initiation in CD4% (17% vs 22%; p60 months (adjusted HR 3.2; 95% CI 1.2 to 9.1). CONCLUSIONS: Good clinical outcomes in HIV-infected children on ART are possible in a rural, decentralised service. Few young children are on ART, highlighting the urgent need to identify HIV-exposed infants. [ABSTRACT FROM AUTHOR]