Modelling trends of CD4 counts for patients on antiretroviral therapy (ART): a comprehensive health care clinic in Nairobi, Kenya.

BACKGROUND: In resource-limited settings, changes in CD4 counts constitute an important component in patient monitoring and evaluation of treatment response as these patients do not have access to routine viral load testing. In this study, we quantified trends on CD4 counts in patients on highly active antiretroviral therapy (HAART) in a comprehensive health care clinic in Kenya between 2011 and 2017. We evaluated the rate of change in CD4 cell count in response to antiretroviral treatment. We further assessed factors that influenced time to treatment change focusing on baseline characteristics of the patients and different initial drug regimens used. This was a retrospective study involving 432 naïve HIV patients that had at least two CD4 count measurements for the period. The relationship between CD4 cell count and time was modeled using a semi parametric mixed effects model while the Cox proportional hazards model was used to assess factors associated with the first regimen change. RESULTS: Majority of the patients were females and the average CD4 count at start of treatment was 362.1 [Formula: see text]. The CD4 count measurements increased nonlinearly over time and these trends were similar regardless of the treatment regimen administered to the patients. The change of logarithm CD4 cell count rises fast for in the first 450 days of antiretroviral initiation. The average time to first regimen change was 2142 days. Tenoforvir (TDF) based regimens had a lower drug substitution(aHR 0.2682, 95% CI:0.08263- 0.8706) compared to Zidovudine(AZT). CONCLUSION: The backbone used was found to be associated with regimen changes among the patients with fewer switches being observed, with the use of TDF when compared to AZT. There was however no significant difference between TDF and AZT in terms of the rate of change in logarithm CD4 count over time.

Implementing an intensified mentorship approach towards accelerated medical laboratory accreditation in 10 counties in Kenya.

Background: Despite Kenya's roll-out of the Strengthening Laboratory Management Towards Accreditation programme in 2010, most laboratories had not made significant or tangible improvements towards accreditation by 2016. In April 2016, the University of Maryland, Baltimore enrolled 27 facilities in the standard Strengthening Laboratory Management Towards Accreditation programme. Objective: This study aimed to describe and evaluate the implementation of an intensified mentorship strategy on laboratory accreditation. Methods: In October 2017, the University of Maryland, Baltimore implemented intensive mentorship in 27 hospital laboratories in Nairobi, Kiambu, Meru, Embu, Muranga, Nyeri, Laikipia, Nyandarua, Tharaka-Nithi, and Kirinyaga counties in Kenya. Laboratories were paired with competent mentors whose skills were matched to facility gaps. Baseline and follow-up assessments were done between April 2016 and March 2019 using the World Health Organization's Stepwise Laboratory Quality Improvement Process Towards Accreditation Checklist and overall scores of the 12 Quality System Essentials and star ratings (from zero to five, based on scores) used to evaluate the effectiveness of the intensified mentorship. Results: In September 2017, 14 laboratories scored zero stars, three scored one star, eight scored two stars, one scored three stars, and one laboratory was accredited. By March 2019, eight laboratories were accredited, five scored four stars, 10 scored three stars, three scored two stars, and only one scored one star. The average score change with the intensified approach was 81.5 versus 53.9 for the standard approach. Conclusion: The intensified mentorship strategy resulted in fast-tracked progress towards laboratory accreditation and can be adopted in similar resource-limited settings.

Infectious correlates of HIV-1 shedding in the female upper and lower genital tracts.

OBJECTIVES: To determine the effects of vaginal, cervical, and endometrial infections on shedding of HIV-1 RNA in the female genital tract. DESIGN: Cross-sectional. METHODS: Antiretroviral-naive women from Nairobi, Kenya with CD4 cell counts >or= 350 cells/mul had plasma and endocervical wick samples collected for HIV quantification by real-time RNA reverse transcriptase-polymerase chain reaction. Vaginal and cervical Gram stains and endometrial biopsies were obtained. Vaginal Gram stain was used to diagnose bacterial vaginosis and to quantify Lactobacillus levels. RESULTS: Twenty-six of 50 (52%) women had detectable endocervical HIV-1 RNA with a median endocervical viral load of 1760 copies/ml (range: undetectable to 1 1,030,000 copies/ml). Women with decreased Lactobacillus had 15.8-fold [95% confidence interval (CI), 2.0-123] greater endocervical HIV-1 RNA than women with normal Lactobacillus levels. Women with plasma cell (PC) endometritis [>or= 1 PC/high-power field (hpf)] had a 15.8-fold (95% CI, 2.0-120) higher endocervical HIV RNA level than women without PC endometritis. Both these associations remained after controlling for plasma viral load. Cervicitis (>or= 30 polymorphonuclear leukocytes/hpf), however, was not associated with endocervical HIV-1 RNA shedding (P = 0.81). CONCLUSIONS: In HIV-1-infected, antiretroviral-naive women without symptoms of pelvic inflammatory disease infection, abnormal vaginal flora and inflammatory cells in the endometrium affected HIV-1 shedding from the lower genital tract. These data suggest that both the upper and lower genital tracts contribute to female HIV-1 genital shedding.

Association of hormonal contraception and HIV-seroprevalence in Nairobi, Kenya.

Among women attending family planning clinics in Nairobi, Kenya, the HIV-seroprevalence rates for different contraceptive methods were: depomedroxyprogesterone acetate (DMPA) 431/3279 (13.1%), combination oral contraceptive pill 114/1073 (10.6%), and progesterone-only contraceptive pill (POCP) 45/741 (6.1%). After adjusting for age, marital status, and parity, women using the POCP had a lower HIV seroprevalence (adjusted odds ratio 0.5, 95% confidence interval 0.3-0.7) than women using DMPA. This association was most pronounced among POCP users of lower parity.

Mortality and burden of disease in a cohort of HIV-seropositive adults in Nairobi, Kenya.

The purposes of this study were to measure incidence and determine risk factors associated with opportunistic infections (OIs) and mortality among an HIV-infected cohort in Nairobi, Kenya. Three hundred and eighty-one seropositive ambulatory adults in Nairobi, Kenya were followed from 1997 to 2000 with participants visiting the clinic every two months and when acutely ill. Acute bronchitis was the most frequent diagnosis, followed by sexually transmitted infections, candida vaginitis (among women), fever, diarrhoea, pneumonia, HIV-associated skin rash, oral candidiasis and urinary tract infection. Associations between the frequency of these diagnoses including survival and sociodemographic factors and initial CD4 count were assessed. A CD4 count <200 cells/mL at recruitment was strongly associated with decreased survival (adjusted odds ratio=3.0, 95% confidence interval 1.7-5.1). These findings may help to target high-risk populations and guide OI prevention and treatment strategies including decisions regarding initiation of antiretroviral therapy in sub-Saharan Africa.

The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.

INTRODUCTION: Community Health Workers (CHWs) have been utilised for various primary health care activities in different settings especially in developing countries. Usually when utilised in well defined terms, they have a positive impact. To support Kenya's policy on engagement of CHWs for tuberculosis (TB) control, there is need to demonstrate effects of utilising them. OBJECTIVES: This study assessed TB treatment adherence among patients who utilised CHWs in management of their illness in comparison to those who did not in urban and rural settings. METHODS: A retrospective cohort study was conducted in selected health facilities using standard clinical records for each TB patient registered for treatment between 2005 to 2011. Qualitative data was collected from CHWs and health care providers. RESULTS: The study assessed 2778 tuberculosis patients and among them 1499 (54%) utilized CHWs for their TB treatment. The urban setting in comparison with the rural setting contributed 70% of patients utilising the CHWs (p<0.001). Overall treatment adherence of the cohort was 79%. Categorizing by use of CHWs, adherence among patients who had utilized CHWs was 83% versus 68% among those that had not (p<0.001). In comparison between the rural and urban settings adherence was 76% and 81.5% (p<0.001) respectively and when categorized by use of CHWs it was 73% and 90% (p<0.001) for the rural and urban set ups respectively. Utilisation of CHWs remained significant in enhancing treatment adherence in the cohort with unadjusted and adjusted ORs; OR 2.25, (95% 1.86-2.73) p<0.001 and OR 1.98 (95% 1.51-2.5) p<0.001 respectively. It was most effective in the urban set-up, OR 2.65 (95% 2.02-3.48, p<0.001) in comparison to the rural set up, OR 0.74 (95% 0.56-0.97) p = 0.032. CONCLUSION: Utilisation of CHWs enhanced TB treatment adherence and the best effects were in the urban set-up.

Effect of the levonorgestrel intrauterine device on genital HIV-1 RNA shedding among HIV-1-infected women not taking antiretroviral therapy in Nairobi, Kenya.

The effect of the levonorgestrel-releasing intrauterine device (LNG-IUD) on genital HIV-1 RNA shedding and inflammation among 25 HIV-infected women was evaluated. Blood, endocervical, and cervicovaginal lavage samples were collected from HIV-infected women not taking antiretrovirals before LNG-IUD insertion and 1 month, 3 month, and 6 months thereafter. HIV-1 RNA was quantitated by real-time reverse transcriptase-polymerase chain reaction. Inflammatory markers were measured by enzyme immunoassay. Genital HIV-1 RNA shedding and inflammatory markers did not differ between LNG-IUD placement and month 6, with the exception of interleukin 1ß that increased (0.42 log10; 95% confidence interval: 0.10 to 0.75). The LNG-IUD did not increase genital HIV-1 RNA shedding after 6 months of use.

Associations between genital tract infections, genital tract inflammation, and cervical cytobrush HIV-1 DNA in US versus Kenyan women.

Cervical shedding of HIV-1 DNA may influence HIV-1 sexual transmission. HIV-1 DNA was detected in 250 (80%) of 316 and 207 (79%) of 259 cervical cytobrush specimens from 56 US and 80 Kenyan women, respectively. Plasma HIV-1 RNA concentration was associated with increased HIV-1 DNA shedding among US and Kenyan women. Kenyan women had higher cervicovaginal concentrations of proinflammatory interleukins (IL)-1ß, IL-6, IL-8, and anti-inflammatory secretory leukocyte protease inhibitor compared with US women (all P < 0.01). HIV-1 DNA shedding was associated with increased concentrations of IL-1ß and IL-6 and lower secretory leukocyte protease inhibitor among US women but not Kenyan women.

Interaction between lactobacilli, bacterial vaginosis-associated bacteria, and HIV Type 1 RNA and DNA Genital shedding in U.S. and Kenyan women.

Bacterial vaginosis has been associated with genital HIV-1 shedding; however, the effect of specific vaginal bacterial species has not been assessed. We tested cervicovaginal lavage from HIV-1-seropositive women for common Lactobacillus species: L. crispatus, L. jensenii, and seven BV-associated species: BVAB1, BVAB2, BVAB3, Leptotrichia, Sneathia, Megasphaera, and Atopobium spp. using quantitative PCR. We used linear and Poisson regression to evaluate associations between vaginal bacteria and genital HIV-1 RNA and DNA. Specimens from 54 U.S. (310 visits) and 50 Kenyan women (137 visits) were evaluated. Controlling for plasma viral load, U.S. and Kenyan women had similar rates of HIV-1 RNA (19% of visits vs. 24%; IRR=0.95; 95% CI 0.61, 1.49) and DNA shedding (79% vs. 76%; IRR=0.90; 0.78, 1.05). At visits during antiretroviral therapy (ART), the likelihood of detection of HIV-1 RNA shedding was greater with BVAB3 (IRR=3.16; 95% CI 1.36, 7.32), Leptotrichia, or Sneathia (IRR=2.13; 1.02, 4.72), and less with L. jensenii (IRR=0.39; 0.18, 0.84). At visits without ART, only L. crispatus was associated with a lower likelihood of HIV-1 RNA detection (IRR=0.6; 0.40, 0.91). Vaginal Lactobacillus species were associated with lower risk of genital HIV-1 shedding, while the presence of certain BV-associated species may increase that risk.

Family model of HIV care and treatment: a retrospective study in Kenya.

BACKGROUND: Nyanza Province, Kenya, had the highest HIV prevalence in the country at 14.9% in 2007, more than twice the national HIV prevalence of 7.1%. Only 16% of HIV-infected adults in the country accurately knew their HIV status. Targeted strategies to reach and test individuals are urgently needed to curb the HIV epidemic. The family unit is one important portal. METHODS: A family model of care was designed to build on the strengths of Kenyan families. Providers use a family information table (FIT) to guide index patients through the steps of identifying family members at HIV risk, address disclosure, facilitate family testing, and work to enrol HIV-positive members and to prevent new infections. Comprehensive family-centred clinical services are built around these steps. To assess the approach, a retrospective study of patients receiving HIV care between September 2007 and September 2009 at Lumumba Health Centre in Kisumu was conducted. A random sample of FITs was examined to assess family reach. RESULTS: Through the family model of care, for each index patient, approximately 2.5 family members at risk were identified and 1.6 family members were tested. The approach was instrumental in reaching children; 61% of family members identified and tested were children. The approach also led to identifying and enrolling a high proportion of HIV- positive partners among those tested: 71% and 89%, respectively. CONCLUSIONS: The family model of care is a feasible approach to broaden HIV case detection and service reach. The approach can be adapted for the local context and should continue to utilize index patient linkages, FIT adaption, and innovative methods to package services for families in a manner that builds on family support and enhances patient care and prevention efforts. Further efforts are needed to increase family member engagement.

Prevalence of human papillomavirus genotypes in HIV-1-infected women in Seattle, USA and Nairobi, Kenya: results from the Women's HIV Interdisciplinary Network (WHIN).

BACKGROUND: HIV-infected women have a high prevalence of human papillomavirus (HPV) infection and are more likely to be infected with HPV genotypes that are considered high-risk and have the potential for progressing to cervical cancer. The currently available HPV vaccines protect against specific HPV genotypes that may not be the most important causes of dysplasia and potentially of cervical cancer in HIV-1-infected women. African women have been underrepresented in the studies of global prevalence of HPV genotypes. METHODS: We compared the HPV genotype distribution in HIV-1-infected women from Seattle, Washington, USA and Nairobi, Kenya. The reverse line blot assay and DNA sequencing on cervicovaginal lavage (CVL) specimens were carried out. RESULTS: The most commonly detected HPV types among the women from Seattle were HPV 56, 66, MM8, and 81; in contrast HPV 53, 33, and 58 were the most common HPV genotypes detected in the CVL specimens from the women in the Nairobi cohort. The HPV types associated with low-grade squamous intraepithelial lesions (LSIL) were HPV 53 and HPV 56. HPV types 58, 52, and 16 were associated with high-grade squamous intraepithelial lesions (HSIL). CONCLUSIONS: A better understanding of HPV genotype distribution in the most affected regions of the world is essential to planning effective vaccine strategies if we are unable to demonstrate cross-protection between HPV genotypes included in the present vaccines and those prevalent in the different populations.

Risk factors for pneumonia in urban-dwelling HIV-infected women: a case-control study in Nairobi, Kenya.

In sub-Saharan Africa, respiratory tract infections (RTI) are the leading cause of serious morbidity and mortality in HIV-infected persons. This study sought to investigate demographic, socioeconomic, and environmental risk factors for pneumonia in a cohort of HIV-infected women. The authors performed a nested case-control study in a cohort of HIV-1-infected adults followed in Nairobi, Kenya. Thirty-nine women who developed pneumonia during the follow-up period were selected as cases, and 66 women who did not develop pneumonia were randomly chosen to serve as control subjects. A questionnaire was administered in subjects' homes that assessed demographics, home environment, and socioeconomic status. Women were followed in the cohort for a median of 36.8 months (range, 27.3-39.3). Adjusting for length of follow-up period, factors associated with lower socioeconomic status (lower monthly spending [OR = 3.2; 95% CI, 1.2-8.4 per 10,000 Kenyan shilling decrease], having no savings [OR = 4.1; 95% CI, 1.4-11.9], less sturdy home construction material such as mud or cement walls [OR = 2.6; 95% CI, 1.1-5.9] or dirt floors [OR = 2.8; 95% CI, 1.0-7.6], and lack of a window in the home [OR = 5.5; 95% CI, 0.9-32.2]) and being widowed (OR = 4.3; 95% CI, 1.2-15.1) or single (OR = 3.3; 95% CI, 1.0-11.2) were associated with an increased risk of pneumonia. In multivariate analysis, widowed (AOR = 5.9; 95% CI, 1.3-26.3), single (AOR = 7.7; 95% CI, 1.6-36.4), and divorced (AOR = 4.5; 95% CI, 1.0-20.1) women, those without savings (AOR = 3.7; 95% CI, 1.2-11.7), and those living in more crowded and contagious conditions (AOR = 1.5; 95% CI, 1.1-2.1) remained at increased risk of pneumonia. If confirmed by prospective investigation, these findings could help identify persons and subpopulations of HIV-infected women with the greatest risk of pneumonia.