Prevalence of nonsuppressed viral load and associated factors among HIV-positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population-based nationally representative surveys.

INTRODUCTION: The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months. METHODS: We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART. RESULTS: We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART. CONCLUSIONS: Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence.

Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064.

Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1-4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals.

A comparison of two measures of HIV diversity in multi-assay algorithms for HIV incidence estimation.

BACKGROUND: Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence. METHODS: Both MAAs included two serologic assays (LAg-Avidity assay and BioRad-Avidity assay), HIV viral load, and an HIV diversity assay. HIV diversity was quantified using either a high resolution melting (HRM) diversity assay that does not require HIV sequencing (HRM score for a 239 base pair env region) or sequence ambiguity (the percentage of ambiguous bases in a 1,302 base pair pol region). Samples were classified as MAA positive (likely from individuals with recent HIV infection) if they met the criteria for all of the assays in the MAA. The following performance characteristics were assessed: (1) the proportion of samples classified as MAA positive as a function of duration of infection, (2) the mean window period, (3) the shadow (the time period before sample collection that is being assessed by the MAA), and (4) the accuracy of cross-sectional incidence estimates for three cohort studies. RESULTS: The proportion of samples classified as MAA positive as a function of duration of infection was nearly identical for the two MAAs. The mean window period was 141 days for the HRM-based MAA and 131 days for the sequence ambiguity-based MAA. The shadows for both MAAs were <1 year. Both MAAs provided cross-sectional HIV incidence estimates that were very similar to longitudinal incidence estimates based on HIV seroconversion. CONCLUSIONS: MAAs that include the LAg-Avidity assay, the BioRad-Avidity assay, HIV viral load, and HIV diversity can provide accurate HIV incidence estimates. Sequence ambiguity measures obtained using a commercially-available HIV genotyping system can be used as an alternative to HRM scores in MAAs for cross-sectional HIV incidence estimation.

HIV diversity as a biomarker for HIV incidence estimation: including a high-resolution melting diversity assay in a multiassay algorithm.

Multiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.

Performance of a limiting-antigen avidity enzyme immunoassay for cross-sectional estimation of HIV incidence in the United States.

BACKGROUND: A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers. METHODS AND FINDINGS: Performance of testing algorithms was evaluated using 2,282 samples from individuals in the United States collected 1 month to >8 years after HIV seroconversion. The capacity of selected testing algorithms to accurately estimate incidence was evaluated in three longitudinal cohorts. When used in a single-assay format, the LAg-Avidity assay classified some individuals infected >5 years as assay positive and failed to provide reliable incidence estimates in cohorts that included individuals with long-term infections. We evaluated >500,000 testing algorithms, that included the LAg-Avidity assay alone and MAAs with other biomarkers (BED capture immunoassay [BED-CEIA], BioRad-Avidity assay, HIV viral load, CD4 cell count), varying the assays and assay cutoffs. We identified an optimized 2-assay MAA that included the LAg-Avidity and BioRad-Avidity assays, and an optimized 4-assay MAA that included those assays, as well as HIV viral load and CD4 cell count. The two optimized MAAs classified all 845 samples from individuals infected >5 years as MAA negative and estimated incidence within a year of sample collection. These two MAAs produced incidence estimates that were consistent with those from longitudinal follow-up of cohorts. A comparison of the laboratory assay costs of the MAAs was also performed, and we found that the costs associated with the optimal two assay MAA were substantially less than with the four assay MAA. CONCLUSIONS: The LAg-Avidity assay did not perform well in a single-assay format, regardless of the assay cutoff. MAAs that include the LAg-Avidity and BioRad-Avidity assays, with or without viral load and CD4 cell count, provide accurate incidence estimates.

Screening HIV-infected patients for non-AIDS-defining malignancies.

The use of antiretroviral therapy has reduced mortality and shifted the spectrum of malignancies affecting people living with HIV/AIDS (PLWH). We review guidelines and evidence for screening PLWH for non-AIDS-defining malignancies as compared with the general population. Cervical cancer screening clearly differs for HIV-seropositive women, with two Pap tests 6 months apart in the first year and then annually if normal. The role of cervical human papillomavirus screening has not yet been defined in HIV-seropositive women. Anal cancer screening consists of an annual digital rectal examination, and some (but not all) guidelines also recommend annual anal Pap tests. Screening for breast and colorectal cancer should follow standard, age-appropriate screening recommendations that apply to the general population. Screening HIV-infected men for prostate cancer, as with the general population, lacks a clear benefit. Despite increasing rates of hepatocellular carcinoma and lung cancers among PLWH, there is insufficient evidence to support routine screening.

Longitudinal anthropometric patterns among HIV-infected and HIV-uninfected women.

INTRODUCTION: Previous studies suggest that indicators of central adiposity such as waist-to-hip ratio (WHR) and waist circumference may be altered by HIV infection, antiretroviral treatment, or both. METHODS: Waist and hip circumference and body mass index (BMI) were measured among participants of the Women's Interagency HIV Study semiannually from 1999 to 2004. Generalized linear models evaluated longitudinal patterns of these measures and associations with demographic and clinical characteristics. RESULTS: WHR was significantly larger, whereas BMI and waist and hip circumference were significantly smaller at almost all 11 semiannual visits among 942 HIV-infected women compared with 266 HIV-uninfected women. Among HIV-uninfected women, mean waist and hip circumference and BMI increased over the 5-year study period (waist: +4.1 cm or 4.4%, hip: +3.76 cm or 3.5%, and BMI +2.43 kg/m2 or 8.2%), whereas WHR remained stable. Among the HIV-infected women, waist and hip circumference, BMI, and WHR did not significantly change. Independent predictors of smaller BMI among HIV-infected women included white race, hepatitis C virus seropositivity, current smoking, higher viral load, and lower CD4 cell count. Independent predictors of larger WHR among HIV-infected women included age, white and other non-African American race, higher CD4 cell count, and protease inhibitor (PI) use. Use of a highly active antiretroviral therapy (HAART) regimen was not an independent predictor of BMI or WHR. CONCLUSIONS: HIV-infected women had higher WHRs compared with HIV-uninfected women, despite lower BMIs and waist and hip measurements. BMI and waist and hip circumference increased over 5 years among the HIV-uninfected women but remained stable in the HIV-infected women. Among HIV-infected women, PI use was associated with a larger WHR, although HAART use itself was not appreciably associated with BMI or WHR.