Antiretroviral Treatment Eligibility Research Articles

Opportunistic fungal infections in persons living with advanced HIV disease in Lagos, Nigeria; a 12-year retrospective study.

Nigeria has a large estimated burden of AIDS-related mycoses. We aimed to determine the proportion of patients with AIDS-related opportunistic fungal infections (OFIs) at an urban antiretroviral treatment (ART) centre in Nigeria. A retrospective analysis of a cohort of ART-naïve, HIV-infected patients, assessed for ART eligibility and ARTexperience at the PEPFAR outpatient clinic at Lagos University Teaching Hospital over a 12-year period (April 2004-February 2016) was conducted. During this period, 7,034 patients visited the clinic: 4,797 (68.2%) were female; 6161 patients had a recorded baseline CD4 count, and the median CD4 count was 184 cells/µl (IQR, 84-328). A baseline HIV-1 viral load (VL) was recorded for 5,908 patients; the median VL was 51,194 RNA copies/ml (IQR, 2,316-283,508) and 6,179/7046(88%) had initiated ART. Some 2,456 (34.9%) had a documented opportunistic infections, of whom 1,306 (18.6%) had an opportunistic fungal infection. The total number of OFI episodes was 1,632: oral candidiasis (n=1,473, 90.3%), oesophageal candidiasis (n=118; 8%), superficial mycoses (n=23; 1.6%), Pneumocystis pneumonia (PJP) (n=13; 0.8%), and cryptococcal meningitis(CM) (n=5; 0.4%). 113 (1.6%) were known to have died in the cohort. Approximately 1 in 5 HIV-infected patients in this retrospective cohort, most of whom had initiated ART, were clinically diagnosed with an OFI. Improved access to simple accurate diagnostic tests for CM and PJP should be prioritised for this setting.

Population-level viral suppression among pregnant and postpartum women in a universal test and treat trial.

We sought to determine whether universal 'test and treat' (UTT) can achieve gains in viral suppression beyond universal antiretroviral treatment (ART) eligibility during pregnancy and postpartum, among women living with HIV. A community cluster randomized trial. The SEARCH UTT trial compared an intervention of annual population testing and universal ART with a control of baseline population testing with ART by country standard, including ART eligibility for all pregnant/postpartum women, in 32 communities in Kenya and Uganda. When testing, women were asked about current pregnancy and live births over the prior year and, if HIV-infected, had their viral load measured. Between arms, we compared population-level viral suppression (HIV RNA <500 copies/ml) among all pregnant/postpartum HIV-infected women at study close (year 3). We also compared year-3 population-level viral suppression and predictors of viral suppression among all 15 to 45-year-old women by arm. At baseline, 92 and 93% of 15 to 45-year-old women tested for HIV: HIV prevalence was 12.6 and 12.3%, in intervention and control communities, respectively. Among HIV-infected women self-reporting pregnancy/live birth, prevalence of viral suppression was 42 and 44% at baseline, and 81 and 76% (P = 0.02) at year 3, respectively. Among all 15 to 45-year-old HIV-infected women, year-3 population-level viral suppression was higher in intervention (77%) versus control (68%; P < 0.001). Pregnancy/live birth was a predictor of year-3 viral suppression in control (P = 0.016) but not intervention (P = 0.43). Younger age was a risk factor for nonsuppression in both arms. The SEARCH intervention resulted in higher population viral suppression among pregnant/postpartum women than a control of baseline universal testing with ART eligibility for pregnant/postpartum women.

Leaving no one behind: lessons from implementation of policies for universal HIV treatment to universal health coverage

BackgroundThe third Sustainable Development Goal (SDG − 3) aims to ensure healthy lives and promote well-being for all at all ages. SDG-3 has a specific target on universal health coverage (UHC), which emphasizes the importance of all people and communities having access to quality health services without risking financial hardship. The objective of this study is to review progress towards UHC using antiretroviral treatment (ART) as a case study.MethodsWe used a mixed-methods design including qualitative and quantitative approaches. We reviewed and synthesised the evidence on the evolution of the WHO HIV treatment guidelines between 2002 and 2019. We calculated ART coverage over time by gender, age group, and location. We also estimated ART coverage differences and ratios.FindingsART guidelines have evolved from “treating the sickest” to “treating all”. ART coverage increased globally from under 7% in 2005 to 62% in 2018. There have been successes in increasing ART coverage in all populations and locations. However, progress varies by population and location in many regions. There is inequity in ART coverage: women (68%) versus men (55%), and adults (62%) versus children (54%). This inequity has widened over time, and with expanded ART eligibility criteria. On the other hand, data from at least one high-burden country (Ethiopia) shows that inequity among regions has narrowed over time due to the improvements in the primary health care systems and implementation of the public health approach in the country.ConclusionART coverage has increased at global, regional and national levels to all population groups. However, the gains have not been equitable among locations and populations. Policies towards universality may widen the inequity in resource-limited settings unless countries take precautions and “put the last first”. We argue that primary health care and public health approaches, with multi-sectoral actions and community engagement, are vital to minimize inequity, achieve UHC and leave no one behind.

Implementing 'universal' access to antiretroviral treatment in South Africa: a scoping review on research priorities.

‘Universal’ access to antiretroviral treatment (ART) has become the global standard for treating people living with HIV and achieving epidemic control; yet, findings from numerous ‘test and treat’ trials and implementation studies in sub-Saharan Africa suggest that bringing ‘universal' access to ART to scale is more complex than anticipated. Using South Africa as a case example, we describe the research priorities and foci in the literature on expanded ART access. To do so, we adapted Arksey and O’Malley’s six-stage scoping review framework to describe the peer-reviewed literature and opinion pieces on expanding access to ART in South Africa between 2000 and 2017. Data collection included systematic searches of two databases and hand-searching of a sub-sample of reference lists. We used an adapted socio-ecological thematic framework to categorize data according to where it located the challenges and opportunities of expanded ART eligibility: individual/client, health worker–client relationship, clinic/community context, health systems infrastructure and/or policy context. We included 194 research articles and 23 opinion pieces, of 1512 identified, addressing expanded ART access in South Africa. The peer-reviewed literature focused on the individual and health systems infrastructure; opinion pieces focused on changing roles of individuals, communities and health services implementers. We contextualized our findings through a consultative process with a group of researchers, HIV clinicians and programme managers to consider critical knowledge gaps. Unlike the published literature, the consultative process offered particular insights into the importance of researching and intervening in the relational aspects of HIV service delivery as South Africa’s HIV programme expands. An overwhelming focus on individual and health systems infrastructure factors in the published literature on expanded ART access in South Africa may skew understanding of HIV programme shortfalls away from the relational aspects of HIV services delivery and delay progress with finding ways to leverage non-medical modalities for achieving HIV epidemic control.

Tracing-corrected estimates of disengagement from HIV care and mortality among patients enrolling in HIV care without overt immunosuppression in Tanzania

ABSTRACT In the era of “test and treat”, it is important to understand HIV care outcomes and their determinants in patients presenting to care with early-stage disease. We surveyed 924 adults newly enrolling in HIV care at four clinics in Tanzania before the adoption of universal treatment eligibility, and collected longitudinal clinical data. Participants who defaulted from care were tracked in the community. Cumulative incidence of disengagement from care and death was estimated using competing risk methods. By 12 months after enrollment, 18.2% of patients had disengaged from care and 6.9% had died. Factors associated with disengagement included male sex (adjusted subhazard ratio [aSHR] versus female = 1.75, 95% confidence interval [CI]: 1.06–2.89), provider-initiated HIV diagnosis (aSHR versus self-referred = 1.71, 95% CI: 1.03–2.86), ineligibility for antiretroviral treatment (ART) at enrollment (aSHR versus eligibility = 2.82, 95% CI: 1.84–4.32) and increased anticipated stigma score (aSHR = 1.04 per 5-point increase, 95% CI: 1.02–1.05). Higher life satisfaction score (aSHR = 0.97 per 5-point increase, 95% CI: 0.95–0.99) and having 1–2 close friends (aSHR versus none = 0.58, 95% CI: 0.47–0.71) were protective. The findings highlight the continued importance of social environment for HIV care outcomes and the potential of universal ART eligibility to reduce HIV care attrition.

Impact of Universal Antiretroviral Treatment Eligibility on Rapid Treatment Initiation Among Young Adolescents with Human Immunodeficiency Virus in Sub-Saharan Africa.

Young adolescents with perinatally acquired human immunodeficiency virus (HIV) are at risk for poor care outcomes. We examined whether universal antiretroviral treatment (ART) eligibility policies (Treat All) improved rapid ART initiation after care enrollment among 10-14-year-olds in 7 sub-Saharan African countries. Regression discontinuity analysis and data for 6912 patients aged 10-14-years were used to estimate changes in rapid ART initiation (within 30 days of care enrollment) after adoption of Treat All policies in 2 groups of countries: Uganda and Zambia (policy adopted in 2013) and Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda (policy adopted in 2016). There were immediate increases in rapid ART initiation among young adolescents after national adoption of Treat All. Increases were greater in countries adopting the policy in 2016 than in those adopting it in 2013: 23.4 percentage points (pp) (95% confidence interval, 13.9-32.8) versus 11.2pp (2.5-19.9). However, the rate of increase in rapid ART initiation among 10-14-year-olds rose appreciably in countries with earlier treatment expansions, from 1.5pp per year before Treat All to 7.7pp per year afterward. Universal ART eligibility has increased rapid treatment initiation among young adolescents enrolling in HIV care. Further research should assess their retention in care and viral suppression under Treat All.

Changes in rapid HIV treatment initiation after national "treat all" policy adoption in 6 sub-Saharan African countries: Regression discontinuity analysis.

BackgroundMost countries have formally adopted the World Health Organization’s 2015 recommendation of universal HIV treatment (“treat all”). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts.Methods and findingsWe used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI −2.9 to 3.8; p = 0.804) and Uganda (−4.2 pp, 95% CI −9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16–24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all.ConclusionsOur analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation.

Impact of "test and treat" recommendations on eligibility for antiretroviral treatment: Cross sectional population survey data from three high HIV prevalence countries.

BackgroundLatest WHO guidelines recommend starting HIV-positive individuals on antiretroviral therapy treatment (ART) regardless of CD4 count. We assessed additional impact of adopting new WHO guidelines.MethodsWe used data of individuals aged 15–59 years from three HIV population surveys conducted in 2012 (Kenya) and 2013 (Malawi and South Africa). Individuals were interviewed at home followed by rapid HIV and CD4 testing if tested HIV-positive. HIV-positive individuals were classified as “eligible for ART” if (i) had ever been initiated on ART or (ii) were not yet on ART but met the criteria for starting ART based on country’s guidelines at the time of the survey (Kenya–CD4< = 350 cells/μl and WHO Stage 3 or 4 disease, Malawi as for Kenya plus lifelong ART for all pregnant and breastfeeding women, South Africa as for Kenya plus ART for pregnant and breastfeeding women until cessation of breastfeeding).FindingsOf 18,991 individuals who tested, 4,113 (21.7%) were HIV-positive. Using country’s ART eligibility guidelines at the time of the survey, the proportion of HIV-infected individuals eligible for ART was 60.0% (95% CI: 57.2–62.7) (Kenya), 73.4% (70.8–75.8) (South Africa) and 80.1% (77.3–82.6) (Malawi). Applying WHO 2013 guidelines (eligibility at CD4< = 500 and Option B+ for pregnant and breastfeeding women), the proportions eligible were 82.0% (79.8–84.1) (Kenya), 83.7% (81.5–85.6) (South Africa) and 87.6% (85.0–89.8) (Malawi). Adopting “test and treat” would mean a further 18.0% HIV-positive individuals (Kenya), 16.3% (South Africa) and 12.4% (Malawi) would become eligible. In all countries, about 20% of adolescents (aged 15–19 years), became eligible for ART moving from WHO 2013 to “test and treat” while no differences by sex were observed.ConclusionCountries that have already implemented 2013 WHO recommendations, the burden of implementing “test and treat” would be small. Youth friendly programmes to help adolescents access and adhere to treatment will be needed.

Temporal Improvements in Long-term Outcome in Care Among HIV-infected Children Enrolled in Public Antiretroviral Treatment Care

Increasing numbers of children are requiring long-term HIV care and antiretroviral treatment (ART) in public ART programs in Africa, but temporal trends and long-term outcomes in care remain poorly understood. We analyzed outcomes in a longitudinal cohort of infants (<2 years of age) and children (2-10 years of age) enrolling in a public tertiary ART center in Zimbabwe over an 8-year period (2004-2012). The clinic enrolled 1644 infants and children; the median age at enrollment was 39 months (interquartile range: 14-79), with a median CD4% of 17.0 (interquartile range: 11-24) in infants and 15.0 (9%-23%) in children (P = 0.0007). Among those linked to care, 33.5% dropped out of care within the first 3 months of enrollment. After implementation of revised guidelines in 2009, decentralization of care and increased access to prevention of mother to child transmission services, we observed an increase in infants (48.9%-68.3%; P < 0.0001) and children (48.9%-68.3%; P < 0.0001) remaining in care for more than 3 months. Children enrolled from 2009 were younger, had lower World Health Organization clinical stage, improved baseline CD4 counts than those who enrolled in 2004-2008. Long-term retention in care also improved with decreasing risk of loss from care at 36 months for infants enrolled from 2009 (aHR: 0.57; 95% confidence interval: 0.34-0.95; P = 0.031). ART eligibility at enrollment was a significant predictor of long-term retention in care, while delayed ART initiation after 5 years of age resulted in failure to fully reconstitute CD4 counts to age-appropriate levels despite prolonged ART. Significant improvements have been made in engaging and retaining children in care in public ART programs in Zimbabwe. Guideline and policy changes that increase access and eligibility will likely to continue to support improvement in pediatric HIV outcomes.

Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia.

BackgroundAlthough randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia’s HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs.Methods and findingsWe analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28–41], median CD4 268 cells/μL [IQR 134–430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%–16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%–6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%–13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%–49.9%), 13.6% increase in retention at six months (95% CI, 7.3%–20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%–41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%–46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome.ConclusionsIn this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards.

CD4 cell count variability with repeat testing in South Africa: Should reporting include both absolute counts and ranges of plausible values?

Although eligibility for antiretroviral treatment is no longer based on CD4 thresholds, CD4 testing remains important. Variation in CD4 cell count complicates initiation of antibiotic prophylaxis, differential diagnoses and assessments of immunological recovery. Five hundred and fifty-three HIV-positive antiretroviral-naïve adults, recruited from inner-city clinics, had three serial CD4 cell count tests. Test 1 was mostly done in a laboratory network supporting primary care clinics, while Tests 2 and 3 were performed in a tertiary-level laboratory. Reproducibility was assessed through Bland-Altman limits of agreement and coefficients of variation. Participants, a mean age of 34 years and mostly female (57%), had a median 203 CD4 cells/μL (Test 1). Seventeen per cent classified as having advanced HIV disease (CD4 cell count < 200 cells/µL) on Test 1 had a CD4 cell count > 200 cells/µL on Tests 2 and 3. Mean differences between tests were <10 cells/µL for all comparisons. Limits of agreement for Tests 1 and 2 were -106.9 to 112.7 and coefficient of variation 15. Corresponding figures for Tests 2 and 3 were -88.2 to 103.4, and 13. Means of tests were similar, suggesting no systematic measurement differences, despite testing being done at different times. Variations were, however, considerable in many instances, though smaller in testing done in the same laboratory. CD4 cut-offs must not be applied rigidly, but rather constitute one amongst many factors used to guide patient care. Moreover, given the difficulties in determining whether CD4 changes are due to HIV disease, or other biological and laboratory factors, CD4 laboratory reports should include a range of plausible values, not only the absolute count.

HIV treatment eligibility expansion and timely antiretroviral treatment initiation following enrollment in HIV care: A metaregression analysis of programmatic data from 22 countries.

BackgroundThe effect of antiretroviral treatment (ART) eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to “crowding out” of sicker patients.Methods and findingsWe examined changes in timely ART initiation (within 6 months) at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naïve patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015. Half of the sites included in this analysis were from Southern Africa, one-third were from East Africa, and the remainder were from the Asia-Pacific, Central Africa, North America, and South and Central America regions. The median age of patients enrolling in care at contributing sites was 33.5 years, and the median percentage of female patients at these clinics was 62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI-ART) before and after major expansions of ART eligibility (i.e., expansion to treat persons with CD4 ≤ 350 cells/μL [145 sites in 22 countries] and CD4 ≤ 500 cells/μL [152 sites in 15 countries]). Random effects metaregression models were used to estimate absolute changes in CI-ART at each site before and after guideline expansion. The crude pooled estimate of change in CI-ART was 4.3 percentage points (95% confidence interval [CI] 2.6 to 6.1) after ART eligibility expansion to CD4 ≤ 350, from a baseline median CI-ART of 53%; and 15.9 percentage points (pp) (95% CI 14.3 to 17.4) after ART eligibility expansion to CD4 ≤ 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART were observed among those newly eligible for treatment (18.2 pp after expansion to CD4 ≤ 350 and 47.4 pp after expansion to CD4 ≤ 500), with no change or small increases among those eligible under prior guidelines (CD4 ≤ 350: −0.6 pp, 95% CI −2.0 to 0.7 pp; CD4 ≤ 500: 4.9 pp, 95% CI 3.3 to 6.5 pp). For ART eligibility expansion to CD4 ≤ 500, changes in CI-ART were largest among younger patients (16–24 years: 21.5 pp, 95% CI 18.9 to 24.2 pp). Key limitations include the lack of a counterfactual and difficulty accounting for secular outcome trends, due to universal exposure to guideline changes in each country.ConclusionsThese findings underscore the potential of ART eligibility expansion to improve the timeliness of ART initiation globally, particularly for young adults.

Effect of point-of-care CD4 cell count results on linkage to care and antiretroviral initiation during a home-based HIV testing campaign: a non-blinded, cluster-randomised trial

HIV disease staging with referral laboratory-based CD4 cell count testing is a key barrier to the initiation of antiretroviral treatment (ART). Point-of-care CD4 cell counts can improve linkage to HIV care among people living with HIV, but its effect has not been assessed with a randomised controlled trial in the context of home-based HIV counselling and testing (HBCT). We did a two-arm, cluster-randomised, controlled efficacy trial in two districts of western Kenya with ongoing HBCT. Housing compounds were randomly assigned (1:1) to point-of-care CD4 cell counts (366 compounds with 417 participants) or standard-of-care (318 compounds with 353 participants) CD4 cell counts done at one of three referral laboratories serving the study catchment area. In each compound, we enrolled people with HIV not engaged in care in the previous 6 months. All participants received post-test counselling and referral for HIV care. Point-of-care test participants received additional counselling on the result, including ART eligibility if CD4 was less than 350 cells per μL, the cutoff in Kenyan guidelines. Participants were interviewed 6 months after enrolment to ascertain whether they sought HIV care, verified through chart reviews at 23 local clinics. The prevalence of loss to follow-up at 6 months (LTFU) was listed as the main outcome in the study protocol. We analysed linkage to care at 6 months (defined as 1-LTFU) as the primary outcome. All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02515149. We enrolled 770 participants between July 1, 2013, and Feb 28, 2014. 692 (90%) had verified linkage to care status and 78 (10%) were lost to follow-up. Of 371 participants in the point-of-care group, 215 (58%) had linked to care within 6 months versus 108 (34%) of 321 in the standard-of-care group (Cox proportional multivariable hazard ratio [HR] 2·14, 95% CI 1·67-2·74; log rank p<0·0001). Point-of-care CD4 cell counts in a resource-limited HBCT setting doubled linkage to care and thereby improved ART initiation. Given the substantial economic and logistic hindrances to providing ART for all people with HIV in resource-limited settings in the near term, point of care CD4 cell counts might have a role in prioritising care and improving linkage to care. US Centers for Disease Control and Prevention.

Increased Access to Antiretroviral Therapy Is Associated with Reduced Maternal Mortality in Johannesburg, South Africa: An Audit from 2003-2012.

ObjectiveTo assess the impact of expanded access to antiretroviral treatment (ART) on maternal mortality in Johannesburg, South Africa between 2003 and 2012.MethodsAudit of patient files, birth registers and death certificates at a tertiary level referral hospital. Cause of death was assigned independently, by two reviewers. We compared causes of deaths and the maternal mortality ratios (MMR, deaths/100,000 live births) over three periods corresponding to changes in government policy on ART provision: period one, 2003–2004 (pre-ART); period two, 2005–2009 (ART eligibility with CD4 count <200cells/μL or WHO stage 4 disease); and period three, 2010–2012 (eligibility with CD4 count <350 cells/μL).ResultsThere were 232 deaths and 80,376 deliveries in the three periods. The proportion of pregnant women tested for HIV rose from 43.4% in 2003 to 94.6% in 2012. MMR was 301, 327 and 232 in the three periods, (p = 0.10). The third period MMR was lower than the first and second combined (p = 0.03). Among HIV-positive women, the MMR fell from 836 in the first time period to 431 in the third (p = 0.008) but among HIV negative women it remained unchanged over the three periods, averaging 148. Even in the third period, however, the MMR among HIV-infected women was 3-fold higher than in other women. Mortality from direct obstetric causes such as hemorrhage did not decline over time, but deaths from tuberculosis and HIV-associated malignancy did. In 38.3% of deaths, women had not attended antenatal care.ConclusionHigher coverage of HIV testing and ART has substantially reduced MMR in this hospital setting. Though the gap in MMR between women with and without HIV narrowed, a third of deaths still remain attributable to HIV. Lowering overall MMR will require further strengthening of HIV services, increased antenatal care coverage, and improved care for obstetric emergencies at all levels of care.

Universal Antiretroviral Treatment Eligibility for Children and Adolescents Living With HIV: A New Era.

Antiretroviral treatment coverage for children living with HIV is low, and new efforts are underway to expand eligibility so that all children and adolescents qualify for the treatment regardless of immune suppression or clinical stage. Although recent trials provide direct evidence of the benefit of this approach in adults, no such studies have been performed in children. This report examines the available body of evidence regarding universal HIV treatment for children and adolescents and assesses the benefits and challenges both at individual patient health, as well as at programmatic level. Universal treatment eligibility for children with HIV has great potential for improved growth and neurodevelopment and fewer morbidities for children, and treatment coverage would be expected to increase through guideline simplification. However, concerns regarding toxicities, drug resistance and costs require careful planning. Successful implementation will depend on effective strategies for case-finding, treatment adherence support and program monitoring that will contribute to the growing evidence base for this pivotal pediatric HIV policy shift.

Changing HIV treatment eligibility under health system constraints in sub-Saharan Africa: investment needs, population health gains, and cost-effectiveness.

We estimated the investment needs, population health gains, and cost-effectiveness of different policy options for scaling-up prevention and treatment of HIV in the 10 countries that currently comprise 80% of all people living with HIV in sub-Saharan Africa (Ethiopia, Kenya, Malawi, Mozambique, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe). We adapted the established STDSIM model to capture the health system dynamics: demand-side and supply-side constraints in the delivery of antiretroviral treatment (ART). We compared different scenarios of supply-side (i.e. health system capacity) and demand-side (i.e. health seeking behavior) constraints, and determined the impact of changing guidelines to ART eligibility at any CD4 cell count within these constraints. Continuing current scale-up would require US$178 billion by 2050. Changing guidelines to ART at any CD4 cell count is cost-effective under all constraints tested in the model, especially in demand-side constrained health systems because earlier initiation prevents loss-to-follow-up of patients not yet eligible. Changing guidelines under current demand-side constraints would avert 1.8 million infections at US$208 per life-year saved. Treatment eligibility at any CD4 cell count would be cost-effective, even under health system constraints. Excessive loss-to-follow-up and mortality in patients not eligible for treatment can be avoided by changing guidelines in demand-side constrained systems. The financial obligation for sustaining the AIDS response in sub-Saharan Africa over the next 35 years is substantial and requires strong, long-term commitment of policy-makers and donors to continue to allocate substantial parts of their budgets.

Impact of nurse-delivered community-based CD4 services on facilitating pre-ART care in rural South Africa.

BackgroundHIV testing, diagnosis and treatment programs have expanded globally, particularly in resource-limited settings. Diagnosis must be followed by determination of treatment eligibility and referral to care prior to initiation of antiretroviral treatment (ART). However, barriers and delays along these early steps in the treatment cascade may impede successful ART initiation. New strategies are needed to facilitate the treatment cascade. We evaluated the role of on site CD4+ T cell count phlebotomy services by nurses in facilitating pre-ART care in a community-based voluntary counseling and testing program (CBVCT) in rural South Africa.MethodsWe retrospectively evaluated CBVCT services during five continuous time periods over three years: three periods when a nurse was present on site, and two periods when the nurse was absent. When a nurse was present, CD4 count phlebotomy was performed immediately after HIV testing to determine ART eligibility. When a nurse was absent, patients were referred to their local primary care clinic for CD4 testing. For each period, we determined the proportion of HIV-positive community members who completed CD4 testing, received notification of CD4 count results, as well as the time to test completion and result notification.ResultsBetween 2010 and 2013, 7213 individuals accessed CBVCT services; of these, 620 (8.6 %) individuals were HIV-positive, 205 (33.1 %) were eligible for ART according to South African national CD4 count criteria, and 78 (38.0 % of those eligible) initiated ART. During the periods when a professional nurse was available to provide CD4 phlebotomy services, HIV-positive clients were significantly more likely to complete CD4 testing than during periods when these services were not available (85.5 % vs. 37.3 %, p < 0.001). Additionally, when nurses were present, individuals were significantly more likely to be notified of CD4 results (60.6 % vs. 26.7 %, p <0.001). The time from HIV screening to CD4 test completion was also significantly shorter during nurse presence than nurse absence (median 8 days (IQR 4–19) vs. 35 days (IQR 15–131), p < 0.001).ConclusionsThese findings indicate that in addition to CBVCT, availability of on site CD4 phlebotomy may reduce loss along the pre-ART care cascade and facilitate timely entry into HIV care.

PIMA™ point-of-care testing for CD4 counts in predicting antiretroviral initiation in HIV-infected individuals in KwaZulu-Natal, Durban, South Africa.

IntroductionLimited information is available on the usefulness of the PIMA™ analyser in predicting antiretroviral treatment eligibility and outcome in a primary healthcare clinic setting in disadvantaged communities in KwaZulu-Natal, South Africa.Materials and methodsThe study was conducted under the eThekwini Health Unit, Durban, KwaZulu-Natal. Comparison of the enumeration of CD4+ T-cells in 268 patients using the PIMA™ analyser and the predicate National Health Laboratory Services (NHLS) was undertaken during January to July 2013. Bland-Altman analysis to calculate bias and limits of agreement, precision and levels of clinical misclassification at various CD4+ T-cell count thresholds was performed.ResultsThere was high precision of the PIMA™ control bead cartridges with low and normal CD4+ T-cell counts using three different PIMA™ analysers (%CV < 5). Under World Health Organization (WHO) guidelines (≤ 500 cells/mm3), the sensitivity of the PIMA™ analyser was 94%, specificity 78% and positive predictive value (PPV) 95%. There were 24 (9%) misclassifications, of which 13 were false-negative in whom the mean bias was 149 CD4+ T-cells/mm3. Most (87%) patients returned for their CD4 test result but only 67% (110/164) of those eligible (≤ 350 cells/mm3) were initiated on antiretroviral therapy (ART) with a time to treatment of 49 days (interquartile range [IQR], 42–64 days).ConclusionThere was adequate agreement between PIMA™ analyser and predicate NHLS CD4+ T-cell count enumeration (≤ 500 cells/mm3) in adult HIV-positive individuals. The high PPV, sensitivity and acceptable specificity of the PIMA™ analyser technology lend it as a reliable tool in predicting eligibility and rapid linkage to care in ART programmes.

Prospects for HIV control in South Africa: a model-based analysis

BackgroundThe goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence.ObjectiveThis study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions.DesignA mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015–2035) to each epidemiological parameter.ResultsHIV incidence in SA adults (ages 15–49) is expected to decline from 1.4% in 2011–2012 to 0.29% by 2035 (95% CI: 0.10–0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r=−0.56), the level of condom use in non-marital relationships (r=−0.40), the phase-in of intensified risk-reduction counselling for HIV-positive adults (r=0.29), the uptake of medical male circumcision (r=−0.24) and the phase-in of universal ART eligibility (r=0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r=0.70) and the rate of ART initiation during pregnancy (r=−0.16).ConclusionsThe virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long-term HIV incidence declines in South Africa.

Cascade of HIV care and population viral suppression in a high-burden region of Kenya.

Introduction:Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation – especially HIV incidence, population viral load, and ART eligibility – is rare in sub-Saharan Africa.Design/methods:To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 15–59 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4+ cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections.Results:Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.0–25.2] and 1.9 new cases/100 person-years (95% CI 1.1–2.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.8–61.9) were previously diagnosed, 53.1% (95% CI 50.5–55.7) were receiving care, and 39.7% (95% CI 37.1–42.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3–62.7) to 82.0% (95% CI 79.5–84.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4+ cell count (500–749 vs. ≥750 cells/μl, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.20–0.60, P < 0.01).Conclusion:This study demonstrates how population-level data can help optimize HIV programs. Based on these results, new regional programs are prioritizing diagnosis and expanding ART eligibility, key steps to reach undetectable viral load.