Integrating pre-exposure prophylaxis of HIV infection into family planning services: a scoping review.

INTRODUCTION: The aim of this review was to map evidence of integrating pre-exposure prophylaxis (PrEP) for HIV prevention into family planning services. A comprehensive package, using a combination of PrEP and contraceptive delivery, could reduce the number of new HIV infections and/or unintended pregnancies for at-risk women and adolescent girls. METHODS: A scoping literature search was conducted between August 2020 and October 2020. After developing the review question, electronic databases (MEDLINE, Embase, Cochrane Library, Global Health, Web of Science) were systematically reviewed. All types of articles published from 2012 to August 2020 in English were included. The intended outcome was to identify barriers and enablers of integrating services at the client-level and provider-level. RESULTS: 38 articles met inclusion criteria, with 16 from low-and middle-income countries and 22 from high-income countries. Barriers at the client-level included a lack of risk perception associated with low uptake and continuation of PrEP and pill burden; and at the provider-level, barriers included a lack of studies on cost-effectiveness of integrating services and provider training and knowledge. Facilitators included the initiation of PrEP and contraception at the same time and by the same provider or HIV self-testing. CONCLUSION: Mapping and synthesising current evidence, this review identified key barriers and facilitators for the integration of PrEP into family planning services for women and adolescent girls. In order to address these factors, more implementation research in a variety of settings is needed to meet women's sexual and reproductive health needs globally.

Low-frequency pre-treatment HIV drug resistance: effects on 2-year outcome of first-line efavirenz-based antiretroviral therapy.

OBJECTIVES: Assess the impact of pre-treatment high-frequency and low-frequency drug-resistant HIV variants on long-term outcomes of first-line efavirenz-based antiretroviral therapy (ART). DESIGN: Prospective observational study. METHODS: Participants' pre-treatment plasma RNA had two sections of HIV pol encoding reverse transcriptase sequenced (Illumina, MiSeq) using unique molecular identifiers to detect wild-type (pre-treatment drug-resistant variants less than 1% of viral quasispecies), low-frequency (1-9%) or high-frequency drug-resistant variants (10-100%). Associations between pre-treatment drug resistance and virologic outcomes over 24 months of efavirenz-based ART were assessed for the number and frequency of mutations by drug class and other resistance parameters. RESULTS: Virologic failure was detected in 30 of 352 (9%) and pre-treatment drug-resistant variants were detected in the viral quasispecies of 31 of 352 (9%) participants prescribed efavirenz-based ART. Survival analyses revealed statistically significant associations between pre-treatment drug resistance at low (P < 0.0001) and high (P < 0.001) frequencies, at oligonucleotide ligation assay (OLA) (P < 0.00001) and non-OLA (P < 0.01) codons, to a single-antiretroviral class (P < 0.00001), and a shorter time to virologic failure of efavirenz-based ART. Regression analyses detected independent effects across resistance categories, including both low-frequency (P < 0.01) and high-frequency (P < 0.001) drug-resistant variants. CONCLUSION: We observed that pre-treatment HIV drug resistance detected at low frequencies increased the risk of virologic failure over 24 months of efavirenz-based ART, but that most failures, regardless of drug-resistant variants' frequencies, were detected within a year of ART initiation. These observations suggest that when efavirenz-based ART is prescribed, screening for pre-treatment drug resistance by an assay capable of detecting low-frequency variants, including OLA, may guide clinicians to prescribe more effective ART.

Hormonal contraception and HIV acquisition among women: an updated systematic review.

OBJECTIVE: To update a 2016 systematic review on hormonal contraception use and HIV acquisition. METHODS: We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses. RESULTS: In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk. CONCLUSIONS: High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.

Evaluation of the management of pretreatment HIV drug resistance by oligonucleotide ligation assay: a randomised controlled trial.

BACKGROUND: Although experts have recommended testing for pretreatment drug resistance (PDR) before antiretroviral therapy (ART) initiation, there is little evidence to support its implementation. We aimed to establish whether an inexpensive point mutation assay can improve virological suppression by identifying PDR to guide drug selection for ART in a lower-middle income country. METHODS: Investigators did an open-label, randomised controlled trial at three HIV treatment sites in Kenya: two in Nairobi and one in rural Maseno. Individuals (aged ≥2 years) were eligible to participate if they were confirmed HIV-seropositive, qualified for first-line ART, planned to reside in the area for more than 1 year, and provided informed consent. We randomly assigned participants (1:1) to either PDR testing by oligonucleotide ligation assay (OLA) to guide selection of ART or to standard of care, which did not include OLA testing. The OLA-guided therapy group had pre-ART peripheral blood mononuclear cells evaluated for drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) at codons Lys103Asn, Tyr181Cys, Gly190Ala, and to lamivudine at Met184Val, and when at least one drug-resistant codon was detected in a participant's pre-ART specimen, clinicians were directed to prescribe protease inhibitor-based second-line ART. Those without detected resistance and those who were randomised to standard of care received NNRTI-based first-line ART. The primary outcome was plasma HIV-1 RNA of at least 400 copies per mL at 4, 8, or 12 months after ART initiation, which defined virological failure, assessed in all participants who received treatment (data were censored for those lost-to-follow-up or who died). The study has been completed and is registered with ClinicalTrials.gov, NCT01898754. FINDINGS: We screened 1198 participants between May 28, 2013, and Nov 4, 2014, of whom 991 (83%) were enrolled (492 received OLA and 495 received standard of care; four did not begin treatment). 93 participants (prevalence 9·4%) had PDR (95% CI 7·7-11·4). 34 (8·5%) of 400 participants in the OLA group had virological failure at month 12 of ART (95% CI 6·0-11·7) compared with 39 (9·7%) of 402 (7·0-13·0) in the standard-of-care group (log-rank p=0·26). Among participants with PDR, virological failure was lower in the OLA-guided therapy group than in the standard-of-care group: five (14%) of 35 compared with 13 (50%) of 26; p=0·0020). Among those prescribed NNRTI-based ART, participants given efavirenz were less likely to have virological failure than were those receiving nevirapine (odds ratio 0·37, 95% CI 0·22-0·62; p<0·0001). The OLA-guided therapy group had 39 serious non-lethal adverse events and 34 deaths. The standard-of-care group had 34 severe adverse events and 43 deaths, differences that were not significant. Adverse events judged to potentially be due to ART were few and similar between groups, with 17 (16%) in the OLA-guided therapy group and 16 (16%) in the standard-of-care group (p=0·90). INTERPRETATION: Our finding that OLA testing for PDR reduced virological failure in only those with specific PDR mutations suggests that PDR poses less of a risk for virological failure than that predicted by past prevalence estimates, and that the value of PDR testing to reduce virological failure should be assessed for antiretroviral treatment regimens. FUNDING: US National Institutes of Health.

Utilization of healthcare services among Chinese migrants in Kenya: a qualitative study.

BACKGROUND: The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya. METHODS: Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes. RESULTS: Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care. CONCLUSIONS: Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.

Minority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan women.

OBJECTIVES: Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure DESIGN/METHODS:: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure. RESULTS: Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all P < 0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing. CONCLUSION: Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.

Higher prevalence of viral control in HIV-1-infected women in serodiscordant relationships.

BACKGROUND: HIV-1-discordant couples that remain discordant despite repeated exposure may differ from the general population in their distribution of transmission risk factors, including low plasma viral load (PVL) in the infected partner even in the absence of antiretroviral therapy (ART). METHODS: We followed two cohorts of HIV-1-infected Kenyan women: females in discordant couples (FDC) and female sex workers (FSW). We compared the distribution of undetectable (<150 copies/mL) and low PVL (<1,000 copies/mL) between the cohorts using bootstrap methods and exact Poisson regression. RESULTS: We evaluated 296 FDC and 220 FSW. At baseline, FDC were more likely to have undetectable (RR = 6.94, bootstrap 95% CI: 3.47, 20.81) and low PVL (RR = 3.53, bootstrap 95% CI: 2.57, 5.65) than FSW. Similarly, both repeat undetectable PVL (RR = 9.36, bootstrap 95% CI: 6.04, 10.97) and repeat low (RR = 4.99, bootstrap 95% CI: 2.33, 14.04) PVL were more likely among FDC than FSW during follow-up. DISCUSSION: We observed higher prevalence of viral control in FDC compared to FSW in the absence of ART, suggesting potentially higher prevalence of biological HIV resistance factors among discordant couples.

Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort. Methods: We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios. Results: PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). Conclusions: The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance. Clinical Trials Registration: NCT01898754.

Gender-Specific Combination HIV Prevention for Youth in High-Burden Settings: The MP3 Youth Observational Pilot Study Protocol.

BACKGROUND: Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. OBJECTIVE: The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. METHODS: The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. RESULTS: The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (PrEP), conditional cash transfer (CCT), and contraceptives for females; and (4) referrals for HIV care among those identified as HIV-positive. The combination package platform selected is mobile health teams in an integrated services delivery model. A cross-sectional analysis will be conducted to determine the uptake of the interventions. To determine long-term impact, the protocol outlines enrolling selected participants in mutually exclusive longitudinal cohorts (HIV-positive, PrEP, CCT, and HIV-negative) followed by using mobile phone text messages (short message service, SMS) and in-person surveys to prospectively assess prevention method uptake, adherence, and risk compensation behaviors. Cross-sectional and sub-cohort analyses will be conducted to determine intervention packages uptake. CONCLUSIONS: The literature review, focus groups, and modeling indicate that offering age- and gender- specific combination HIV prevention interventions that include biomedical, behavioral, and structural interventions can have an impact on HIV risk reduction. Implementing this protocol will show the feasibility of delivering these services at scale. The MP3 Youth study is one of the few combination HIV prevention intervention protocols incorporating youth- and gender-specific interventions in one delivery setting. Lessons learned from the design of the protocol can be incorporated into the national guidance for combination HIV prevention for youth in Kenya and other high-burden SSA settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01571128; http://clinicaltrials.gov/ct2/show/NCT01571128?term=MP3+youth&rank=1 (Archived by WebCite at http://www.webcitation.org/6nmioPd54).

An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women.

OBJECTIVE AND DESIGN: Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data. METHODS: We searched for articles published between 15 January 2014 and 15 January 2016 and hand-searched reference lists. We identified longitudinal studies comparing users of a specific hormonal contraceptive method against either nonusers of hormonal contraception or users of another specific hormonal contraceptive method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus non-use of hormonal contraception. RESULTS: We identified 10 new reports of which five were considered 'unlikely to inform the primary question'. We focus on the other five reports, along with nine from the previous review, which were considered 'informative but with important limitations'. The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate, and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher quality studies on DMPA (or nondisaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher quality studies of hazard ratio 1.4. CONCLUSION: Although confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely hazard ratio 1.5 or less. Data for other hormonal contraceptive methods, including norethisterone enanthate, are largely reassuring.

Increasing HIV-1 pretreatment drug resistance among antiretroviral-naïve adults initiating treatment between 2006 and 2014 in Nairobi, Kenya.

Antiretroviral-naïve adults initiating antiretroviral therapy in Nairobi, Kenya were tested for HIV-1 drug resistance at codons K103N, Y181C, G190A, M184V, and K65R using an oligonucleotide ligation assay. Prevalence of pretreatment drug resistance increased from 3.89% in 2006 to 10.93% in 2014 (P < 0.001), and 95% of those with resistance had at least one nonnucleoside reverse transcriptase inhibitor mutation. Resistance to tenofovir (K65R) was found in 2014 but not in 2006.

Male Partner Participation in Antenatal Clinic Services is Associated With Improved HIV-Free Survival Among Infants in Nairobi, Kenya: A Prospective Cohort Study.

OBJECTIVE: This prospective study investigated the relationship between male antenatal clinic (ANC) involvement and infant HIV-free survival. METHODS: From 2009 to 2013, HIV-infected pregnant women were enrolled from 6 ANCs in Nairobi, Kenya and followed with their infants until 6 weeks postpartum. Male partners were encouraged to attend antenatally through invitation letters. Men who failed to attend had questionnaires sent for self-completion postnatally. Multivariate regression was used to identify correlates of male attendance. The role of male involvement in infant outcomes of HIV infection, mortality, and HIV-free survival was examined. RESULTS: Among 830 enrolled women, 519 (62.5%) consented to male participation and 136 (26.2%) men attended the ANC. For the 383 (73.8%) women whose partners failed to attend, 63 (16.4%) were surveyed through outreach. In multivariate analysis, male report of previous HIV testing was associated with maternal ANC attendance (adjusted odds ratio = 3.7; 95% CI: 1.5 to 8.9, P = 0.003). Thirty-five (6.6%) of 501 infants acquired HIV or died by 6 weeks of life. HIV-free survival was significantly greater among infants born to women with partner attendance (97.7%) than those without (91.3%) (P = 0.01). Infants lacking male ANC engagement had an approximately 4-fold higher risk of death or infection compared with those born to women with partner attendance (HR = 3.95, 95% CI: 1.21 to 12.89, P = 0.023). Adjusting for antiretroviral use, the risk of death or infection remained significantly greater for infants born to mothers without male participation (adjusted hazards ratio = 3.79, 95% CI: 1.15 to 12.42, P = 0.028). CONCLUSIONS: Male ANC attendance was associated with improved infant HIV-free survival. Promotion of male HIV testing and engagement in ANC/prevention of mother-to-child transmission services may improve infant outcomes.

Building capacity in implementation science research training at the University of Nairobi.

BACKGROUND: Health care systems in sub-Saharan Africa, and globally, grapple with the problem of closing the gap between evidence-based health interventions and actual practice in health service settings. It is essential for health care systems, especially in low-resource settings, to increase capacity to implement evidence-based practices, by training professionals in implementation science. With support from the Medical Education Partnership Initiative, the University of Nairobi has developed a training program to build local capacity for implementation science. METHODS: This paper describes how the University of Nairobi leveraged resources from the Medical Education Partnership to develop an institutional program that provides training and mentoring in implementation science, builds relationships between researchers and implementers, and identifies local research priorities for implementation science. RESULTS: The curriculum content includes core material in implementation science theory, methods, and experiences. The program adopts a team mentoring and supervision approach, in which fellows are matched with mentors at the University of Nairobi and partnering institutions: University of Washington, Seattle, and University of Maryland, Baltimore. A survey of program participants showed a high degree satisfaction with most aspects of the program, including the content, duration, and attachment sites. A key strength of the fellowship program is the partnership approach, which leverages innovative use of information technology to offer diverse perspectives, and a team model for mentorship and supervision. CONCLUSIONS: As health care systems and training institutions seek new approaches to increase capacity in implementation science, the University of Nairobi Implementation Science Fellowship program can be a model for health educators and administrators who wish to develop their program and curricula.

Changes in Vaginal Microbiota and Immune Mediators in HIV-1-Seronegative Kenyan Women Initiating Depot Medroxyprogesterone Acetate.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation. METHODS: In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression. RESULTS: From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3-8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5-11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02). CONCLUSIONS: Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.

Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation.

Human immunodeficiency virus (HIV) is a chronic infection that can be managed by antiretroviral treatment (ART). However, periods of suboptimal viral suppression during lifelong ART can select for HIV drug resistant (DR) variants. Transmission of drug resistant virus can lessen or abrogate ART efficacy. Therefore, testing of individuals for drug resistance prior to initiation of treatment is recommended to ensure effective ART. Sensitive and inexpensive HIV genotyping methods are needed in low-resource settings where most HIV infections occur. The oligonucleotide ligation assay (OLA) is a sensitive point mutation assay for detection of drug resistance mutations in HIV pol. The current OLA involves four main steps from sample to analysis: (1) lysis and/or nucleic acid extraction, (2) amplification of HIV RNA or DNA, (3) ligation of oligonucleotide probes designed to detect single nucleotide mutations that confer HIV drug resistance, and (4) analysis via oligonucleotide surface capture, denaturation, and detection (CDD). The relative complexity of these steps has limited its adoption in resource-limited laboratories. Here we describe a simplification of the 2.5-hour plate-format CDD to a 45-minute paper-format CDD that eliminates the need for a plate reader. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. The assay described makes the OLA easier to perform in low resource laboratories.

The WHO's medical eligibility criteria for contraceptive use: 20 years of global guidance.

PURPOSE OF REVIEW: The purpose of this review is to revisit the inception of the WHO's medical eligibility criteria for contraceptive use (MEC), particularly its objectives and methodology, and to describe its impact over the last 20 years in the field of family planning. New recommendations are summarized from the newly released fifth edition of the guidance. RECENT FINDINGS: Fourteen topics, encompassing over 575 recommendations were reviewed for the MEC, fifth edition. New recommendations include: changes for combined hormonal contraceptive use among postpartum women; progestogen-only methods among breastfeeding women; and women at high risk for HIV infection, women living with HIV, and women living with HIV using antiretroviral therapy and hormonal contraception. New methods reviewed include subcutaneously administered depot medroxyprogesterone acetate, Sino-implant (II), ulipristal acetate, and progesterone-releasing vaginal ring. SUMMARY: Over the past 20 years, the MEC has become a remarkably influential document for practitioners and policy makers in family planning, as it provides up-to-date, evidence-based recommendations for contraceptive use for women with various medical conditions and medically relevant characteristics.

Socio-economic determinants of disease progression among HIV infected adults in Kenya.

BACKGROUND: Socioeconomic determinants have been shown to have an effect on the progression of HIV disease evidenced by studies carried out largely in developed countries. Knowledge of these factors could inform on prioritization of populations during scale up of highly active antiretroviral therapy (HAART) constrained health systems. The objective of this study was to identify socioeconomic correlates of HIV disease progression in an adult Kenyan population. METHODS: We analysed data from 312 HIV positive individuals, drawn from a cohort enrolled in a randomized clinical trial investigating the effectiveness of Acyclovir in the prevention of HIV transmission among serodiscordant couples. In this study we included individuals with CD4 counts ≥ 350 cells/mm(3) and World Health Organization (WHO), clinical stage one or two. The exposure variables measured were: - daily household income available for expenditure, age, gender, housing type and level of formal education. We used a composite outcome of disease progression to WHO clinical stage 3 or 4 or a laboratory outcome of CD4 count below 350 cells/mm(3) after two years of follow-up. Logistic regression was used to determine associations of variables that were found to be significant at univariate analysis, and to control for potential confounders. RESULTS: Seventy eight (25 %) individuals reported HIV disease progression. Majority (79.9 %) were female. The median age was 30 year and 93.6 % had attained a primary level of education. Median CD4 at enrolment into the clinical trial was 564 cells/mm(3); those who had disease progression were enrolled with a significantly (p < 0.001) lower CD4 count. Daily household income available for expenditure adjusted for CD4 count at enrolment was associated significantly (p = 0.04) with HIV disease progression. Disease progression was five times more likely to occur in study subjects with daily income available for expenditure of less than US$1 compared to those with more than US$ 5 available for daily expenditure [adjusted Odds Ratio 4.6 (95 % Confidence Interval 1.4-14.4)]. Disease progression was not associated with age, gender, type of housing or level of education attained (p < 0.05). CONCLUSION: Populations with low household incomes should be considered vulnerable to disease progression and should therefore be prioritized during the scale up of HAART for treatment as prevention.

HIV-1 protease inhibitor drug resistance in Kenyan antiretroviral treatment-naive and -experienced injection drug users and non-drug users.

BACKGROUND: Although injection drug use drives antiretroviral drug resistance, the prevalence of protease inhibitor (PI) resistance among Kenyan IDUs remains undetermined. We, therefore, explored PI resistance mutations and their association with viral load and CD4+ T cell counts in HIV-1 infected IDUs (ART-naive, n = 32; and -experienced, n = 47) and non-drug users (ART-naive, n = 21; and -experienced, n = 32) naive for PI treatment from coastal Kenya. RESULTS: Only IDUs harboured major PI resistance mutations consisting of L90M, M46I and D30 N among 3 (6.4 %) ART-experienced and 1 (3.1 %) -naive individuals. Minor PI mutations including A71T, G48E, G48R, I13V, K20I, K20R, L10I, L10V, L33F, L63P, T74S, V11I, and V32L were detected among the ART-experienced (36.2 vs. 46.9 %) and -naive (43.8 vs. 66.7 %) IDUs and non-drug users, respectively. All the four IDUs possessing major mutations had high viral load while three presented with CD4+ T cell counts of <500 cells/ml. Among the ART-naive non-drug users, CD4+ T cell counts were significantly lower in carriers of minor mutations compared to non-carriers (P < 0.05). CONCLUSION: Transmitted drug resistance may occur in IDUs underscoring the need for genotyping resistance before initiating PI treatment.