Comparison of AmpFire and MY09/11 assays for HPV genotyping in anogenital specimen of Rwandan men who have sex with men.

Introduction: The AmpFire HPV genotyping Assay (Atila Biosystems, Mountain View, CA, USA) is a new test for which there are few data regarding its analytic performance and reliability. Using anal and penile swab specimens from a cohort study of men who have sex with men (MSM) in Rwanda, we compared high-risk HPV (hrHPV) detection by AmpFire done at two laboratories, one at University of California San Francisco (UCSF) and the other Rwanda Military Hospital, and well-validated MY09/11-based assay done at UCSF. Methods: Anal and penile specimens collected from 338 MSM from March 2016 to September 2016 were tested for high-risk HPV genotypes (hrHPV) by MY09/11, AmpFire UCSF and AmpFire RMH. Cohen's kappa coefficient was used to test for reproducibility. Results: The hrHPV positivity by MY09/11 and AmpFire UCSF was 13% and 20.7% (k = 0.73) for anal specimens and was 26.3% and 32.6% (k = 0.67) for penile specimens. Specifically, good reproducibility was for types 16 and 18 (k = 0.69 and k = 0.71) for anal specimens and (k = 0.50 and k = 0.72) for penile specimens. The hrHPV positivity by AmpFire at UCSF and RMH was 20.7% for both laboratories (k = 0.87) for anal specimens and was 34.9% and 31.9% (k = 0.89) for penile specimens. Specifically, excellent reproducibility was for types 16 and 18 for anal specimens (k = 0.80 and k = 1.00) and penile specimens (k = 0.85 and k = 0.91). Conclusion: Results show that MY09/11 and AmpFire assays have good reproducibility while the AmpFire UCSF and RMH assays have excellent reproducibility. These results show that AmpFire is a promising HPV genotyping test.

Same-Day Antiretroviral Therapy Initiation as a Predictor of Loss to Follow-up and Viral Suppression Among People With Human Immunodeficiency Virus in Sub-Saharan Africa.

BACKGROUND: Treat-All guidelines recommend initiation of antiretroviral therapy (ART) for all people with HIV (PWH) on the day of diagnosis when possible, yet uncertainty exists about the impact of same-day ART initiation on subsequent care engagement. We examined the association of same-day ART initiation with loss to follow-up and viral suppression among patients in 11 sub-Saharan African countries. METHODS: We included ART-naive adult PWH from sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium who enrolled in care after Treat-All implementation and prior to January 2019. We used multivariable Cox regression to estimate the association between same-day ART initiation and loss to follow-up and Poisson regression to estimate the association between same-day ART initiation and 6-month viral suppression. RESULTS: Among 29 017 patients from 63 sites, 18 584 (64.0%) initiated ART on the day of enrollment. Same-day ART initiation was less likely among those with advanced HIV disease versus early-stage disease. Loss to follow-up was significantly lower among those initiating ART ≥1 day of enrollment, compared with same-day ART initiators (20.6% vs 27.7%; adjusted hazard ratio: .66; 95% CI .57-.76). No difference in viral suppression was observed by time to ART initiation (adjusted rate ratio: 1.00; 95% CI: .98-1.02). CONCLUSIONS: Patients initiating ART on the day of enrollment were more frequently lost to follow-up than those initiating later but were equally likely to be virally suppressed. Our findings support recent World Health Organization recommendations for providing tailored counseling and support to patients who accept an offer of same-day ART.

How early is too early? Challenges in ART initiation and engaging in HIV care under Treat All in Rwanda-A qualitative study.

INTRODUCTION: HIV treatment guidelines recommend that all people living with HIV (PLWH) initiate antiretroviral therapy (ART) as soon as possible after diagnosis (Treat All). As Treat All is more widely implemented, an increasing proportion of PLWH are likely to initiate ART when they are asymptomatic, and they may view the relative benefits and risks of ART differently than those initiating at more advanced disease stages. To date, patient perspectives of initiating care under Treat All in sub-Saharan Africa have not been well described. METHODS: From September 2018 to March 2019, we conducted individual, semi-structured, qualitative interviews with 37 patients receiving HIV care in two health centers in Kigali, Rwanda. Data were analyzed using a mixed deductive and inductive thematic analysis approach to describe perceived barriers to, facilitators of and acceptability of initiating and adhering to ART rapidly under Treat All. RESULTS: Of 37 participants, 27 were women and the median age was 31 years. Participants described feeling traumatized and overwhelmed by their HIV diagnosis, resulting in difficulty accepting their HIV status. Most were prescribed ART soon after diagnosis, yet fear of lifelong medication and severe side effects in the immediate period after initiating ART led to challenges adhering to therapy. Moreover, because many PLWH initiated ART while healthy, taking medications and attending appointments were visible signals of HIV status and highly stigmatizing. Nonetheless, many participants expressed enthusiasm for Treat All as a program that improved health as well as health equity. CONCLUSION: For newly-diagnosed PLWH in Rwanda, initiating ART rapidly under Treat All presents logistical and emotional challenges despite the perceived benefits. Our findings suggest that optimizing early engagement in HIV care under Treat All requires early and ongoing intervention to reduce trauma and stigma, and promote both individual and community benefits of ART.

A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women.

HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.

Challenges and opportunities associated with cervical cancer screening programs in a low income, high HIV prevalence context.

BACKGROUND: Cervical cancer is a leading cause of death among Cameroon women. The burden of cervical cancer is in part traceable to the inadequate understanding of socio-contextual determinants of access to screening and prevention opportunities. We explored multilevel individual, community and structural factors that facilitate or inhibit cervical cancer prevention in women at risk in a low-income, high HIV prevalence context. METHODS: We utilized an exploratory qualitative approach to obtain data through focus group discussions and in-depth interviews from May to August, 2018. A two-stage purposive sampling strategy was used to select 80 women and 20 men who participated in 8 focus group discussions and 8 in-depth interviews. The socio-ecological model guided data analyses to identify micro-, meso-, and macro-level determinants of cervical cancer screening. RESULTS: Micro-level factors including lack of awareness and knowledge about cervical cancer, lack of access to information, excessive cost of cervical cancer screening, low risk perceptions, and poor health seeking behaviors were major barriers for women seeking cervical cancer screening. Meso-level factors, such as social networks, socio-cultural norms, perceptions of the role of men and HIV-related stigma when screening is integrated into HIV care, also engender negative attitudes and behaviors. Macro-level barriers to cervical cancer screening included poorly equipped health facilities and a lack of national cancer prevention policies and programs. CONCLUSION: In the context of the call for elimination of cervical cancer as a public health problem, our findings highlight challenges and opportunities that should be considered when implementing interventions to increase uptake of cervical cancer screening in low-middle income settings.

Acceptability of Self-Sampling for Cervical Cancer Screening Among Women Living With HIV and HIV-Negative Women in Limbé, Cameroon.

Introduction: Like many countries in Sub-Saharan Africa, Cameroon has a high burden of cervical cancer and low availability and uptake of screening. Self-collection has the potential to increase the uptake of cervical cancer screening among Cameroon women. This paper explores patient and community insights surrounding self-collection among women living with HIV and HIV[-] women as well as the barriers and facilitators to obtaining and utilizing self-collected specimens in cervical cancer screening programs. Materials and methods: We utilized an exploratory qualitative approach to obtain data through focus group discussions and in-depth interviews during data collection that took place from May to August 2018. A two-stage sampling strategy was used to select 80 women who participated in six focus group discussions and eight in-depth interviews. We utilized the socio-ecological framework to guide data analysis. Results: All participants indicated that self-sampling was an acceptable method of specimen collection and should be offered as an option for cervical cancer screening in Cameroon. Whereas, most women, regardless of HIV status, preferred the option for self-collection, barriers were identified, such as lack of education about self-collection procedure, being uncomfortable, embarrassed or in pain from the procedure, fear of consequences, perceived competence about ability to self-collect and privacy and confidentiality. We also found that HIV-related stigma was a major concern for HIV[-] women that could prevent them from accessing cervical cancer screening integrated within HIV treatment settings. Conclusions: To promote self-collection for cervical cancer screening, educational interventions with both patients and providers are necessary to increase knowledge of and overall willingness to utilize self-collection. Further research is recommended to examine the role of stigma for HIV[-] women in screening locations associated with HIV treatment.

Social contexts as mediator of risk behaviors in Rwandan men who have sex with men (MSM): Implications for HIV and STI transmission.

INTRODUCTION: Men who have sex with men (MSM) are disproportionately impacted by HIV/AIDS resulting from risky sexual behaviors. Social and contextual factors are known to mediate risk behaviors, but there is limited information about the prevalence of risky sexual practices of Rwandan MSM and the concomitant socio-contextual determinants making it difficult to assess implications for preventing HIV/STI transmission in this key population. METHODS: Using exploratory qualitative design, we obtained socio-contextual information regarding prevalence of risky sexual behavior and assessed implications for HIV/ STIs transmission and preventive measures taken by MSM to improve sexual health and wellbeing. Thirty MSM were recruited to participate in in-depth interviews using respondent-driven sampling from LGBT associations in Kigali. Data were analyzed using standard qualitative data analysis procedures. RESULTS: Respondents' were between 18-40 years old; all completed primary education and are mostly low-socioeconomic status. Risky sexual practices were common, but differed by peculiar individual and contextual factors. Older MSM often reported occasional sexual relations with women to avoid suspicion and social stigma. Younger MSM's risky sexual practices are mostly transactional and mediated by the need for social acceptance and support. Knowledge of STIs was poor, but prevalence, especially of HPV was high. The options for improving sexual wellbeing are limited and mostly clandestine. CONCLUSION: Risky sexual behavior of Rwandan MSM has major implications for HIV/STI transmission. An environment of intense social stigma and social isolation makes it difficult to obtain information or services to improve sexual health. Effective interventions that address individual and contextual determinants of risk and access to health services are urgently needed to limit the consequence of MSM as a bridge for HIV transmission to the general population.

Insomnia symptoms and HIV infection among participants in the Women's Interagency HIV Study.

OBJECTIVES: This study assessed the prevalence of insomnia symptoms among women with and without HIV-infection and examined factors associated with insomnia. DESIGN: Participants (n = 1682) were enrolled in the Women's Interagency HIV Study (WIHS); 69% were infected with HIV. This was a cross-sectional analysis of data from standardized interviewer-administered instruments and physical/gynecological exams. Analysis focused on sociodemographics, sleep measures, depressive symptoms, drug use, alcohol consumption, medications, and HIV-related clinical variables. Women were classified as having symptoms of insomnia if they reported either difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening ≥ 3 times a week in the past 2 weeks. RESULTS: Overall, HIV-infected women were 17% more likely to endorse insomnia symptoms than uninfected women (OR = 1.17, 95% CI: 1.04-1.34, P < 0.05). The adjusted prevalence of insomnia symptoms varied by HIV status and age groups. Among women ages 31-40 years, those with HIV infection were 26% more likely to endorse insomnia symptoms than their counterparts (OR = 1.26, 95% CI: 1.01-1.59, P < 0.05). No significant differences were observed in the likelihood of reporting insomnia symptoms based on HIV treatment type. Multivariate-adjusted regression analyses showed that depression was the most consistent and significant independent predictor of the likelihood of reporting insomnia symptoms across all age strata. CONCLUSIONS: Insomnia symptoms are common among both HIV-infected and uninfected women. Prevalence of insomnia did not vary significantly by HIV status, except among younger women. Younger women with HIV infection are at greater risk for experiencing insomnia symptoms.

Serological detection of human papillomavirus type 16 infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.

Serial measurement of antibodies has not been used to provide evidence of active viral replication of human papillomavirus (HPV). Serum specimens from sequential study visits contributed by 642 human immunodeficiency virus (HIV)-positive and 116 HIV-negative participants enrolled in the Women's Interagency HIV Study were used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors associated with a significant rise were identified using multivariable logistic regression models with generalized estimating equations. Among HIV-positive women, 8.3% of 1,997 pairs showed antibody rises, compared to 6.1% of 361 pairs among HIV-negative women (P = 0.191). For HIV-positive women, rises were associated with current (odds ratio [OR], 23.4; P < 0.001) or past (OR, 8.9; P < 0.001) HPV-16 infection relative to never being HPV-16 infected and with CD4+ cell counts (OR per 100-cell increase, 0.8; P < 0.001) but not with sexual behavior. For HIV-negative women, rises were associated with past (OR, 10.9; P = 0.033) HPV-16 infection relative to no HPV-16, current cigarette smoking (OR, 5.0; P = 0.029) relative to no smoking history, and having 6 to 10 lifetime sexual partners compared to 0 to 5 partners (OR, 9.9; P = 0.036). Serial measurement of HPV-16 serum antibodies is a useful tool for identifying active HPV-16 viral replication. Rises among HIV-positive women may more often result from reactivation of a latent HPV infection in the context of HIV-induced immunosuppression, while rises among HIV-negative women may more often result from reinfection with HPV.

Serum immunoglobulin A response to human papillomavirus type 16 virus-like particles in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.

Serum samples from 2008 human immunodeficiency virus (HIV)-positive and 551 HIV-negative women were tested for immunoglobulin A (IgA) to human papillomavirus (HPV) type 16 capsids. IgA seropositivity was lower than previously reported IgG seropositivity (7% vs. 51%), but, like IgG antibodies, HPV 16 IgA was associated with sexual behavior, cervicovaginal HPV 16 DNA, and cytological abnormalities. IgA seropositivity was higher in HIV-positive women than in HIV-negative women (7.7% vs. 4.9%; P=.02), but the association was lost after adjustment for HPV 16 cervicovaginal infection. IgA, but not IgG, seropositivity was associated with progression to high-grade cytological abnormalities (relative hazard [RH], 2.2 [95% confidence interval, 1.2-4.2]), raising the possibility that an IgA response to HPV 16, as described for other DNA viruses, may be a marker of persistent viral replication. The risk of incident infection with non-16-related HPV types was increased in IgA seropositive women (RH, 1.8 [95% confidence interval, 1.3-2.6]), compared with seronegative women (RH, 2.2 [95% confidence interval, 0.9-5.4]), but there was no difference in the risk of incident HPV 16 or HPV 16-related infections. This may be evidence of partial type-specific or clade-specific immunity conferred by seropositivity to HPV 16 capsids.

Serum immunoglobulin G response to human papillomavirus type 16 virus-like particles in human immunodeficiency virus (HIV)-positive and risk-matched HIV-negative women.

Baseline serum samples from 2815 human immunodeficiency virus (HIV)-positive and 963 HIV-negative women enrolled in 2 cohort studies were tested for immunoglobulin G antibodies to human papillomavirus type 16 (HPV-16) capsids. HPV-16 seropositivity was associated with lifetime number of sex partners (P<.001) among both HIV-positive and HIV-negative women. Approximately 50%-60% of HPV-16 DNA-positive women were HPV-16 positive. HPV-16 seropositivity was associated with HIV infection; however, after adjustment for baseline cervical HPV infection and disease, the association disappeared. Thus, the high seroprevalence of HPV-16 among HIV-positive women may be explained by a high prevalence of HPV of all types. Approximately 50% of HIV-positive women had serological evidence of prior HPV-16 infection, but only approximately 5% had an HPV-16 cervical infection at baseline. Despite the higher prevalence of HPV infection in this group, most HIV-positive women are able to control HPV-16 replication at the cervix, and reactivation, if it occurs, is not very common.