Second-Line Switch to Dolutegravir for Treatment of HIV Infection.

BACKGROUND: Data to inform the switch from a ritonavir-boosted protease inhibitor (PI) to dolutegravir in patients living with human immunodeficiency virus (HIV) infection who do not have genotype information and who have viral suppression with second-line therapy containing a ritonavir-boosted PI have been limited. METHODS: In a prospective, multicenter, open-label trial conducted at four sites in Kenya, we randomly assigned, in a 1:1 ratio, previously treated patients without genotype information who had viral suppression while receiving treatment containing a ritonavir-boosted PI to either switch to dolutegravir or continue the current regimen. The primary end point was a plasma HIV type 1 RNA level of at least 50 copies per milliliter at week 48, assessed on the basis of the Food and Drug Administration snapshot algorithm. The noninferiority margin for the between-group difference in the percentage of participants who met the primary end point was 4 percentage points. Safety up to week 48 was assessed. RESULTS: A total of 795 participants were enrolled, with 398 assigned to switch to dolutegravir and 397 assigned to continue taking their ritonavir-boosted PI; 791 participants (397 in the dolutegravir group and 394 in the ritonavir-boosted PI group) were included in the intention-to-treat exposed population. At week 48, a total of 20 participants (5.0%) in the dolutegravir group and 20 (5.1%) in the ritonavir-boosted PI group met the primary end point (difference, -0.04 percentage points; 95% confidence interval, -3.1 to 3.0), a result that met the criterion for noninferiority. No mutations conferring resistance to dolutegravir or the ritonavir-boosted PI were detected at the time of treatment failure. The incidence of treatment-related grade 3 or 4 adverse events was similar in the dolutegravir group and the ritonavir-boosted PI group (5.7% and 6.9%, respectively). CONCLUSIONS: In previously treated patients with viral suppression for whom there were no data regarding the presence of drug-resistance mutations, dolutegravir treatment was noninferior to a regimen containing a ritonavir-boosted PI when the patients were switched from a ritonavir-boosted PI-based regimen. (Funded by ViiV Healthcare; 2SD ClinicalTrials.gov number, NCT04229290.).

Utilisation of cervical cancer screening among women living with HIV at Kenya's national referral hospital.

Background: In 2009, Kenyatta National Hospital (KNH) integrated cervical cancer screening within HIV care using visual inspection with acetic acid (VIA) and Pap smear cytology. Objectives: We evaluated utilisation of cervical cancer screening and human papillomavirus (HPV) vaccination among women living with HIV (WLHIV) receiving HIV care at KNH. Method: From November 2019 to February 2020, WLHIV aged ≥ 14 years were invited to participate in a survey following receipt of routine HIV services. We assessed awareness of cervical cancer, uptake of cervical cancer screening, uptake of the HPV vaccine, and barriers to utilisation of these services. In a subset of survey participants, focus group discussions (FGDs) were also conducted to identify screening barriers. Results: Overall, 305 WLHIV participated in the survey. Median age was 36 years (interquartile range [IQR]: 28-43), 41% were married, and 38% completed secondary education. Most (90%) had HIV RNA < 1000 copies/mL. Awareness of cervical cancer was high (84%), although only 45% of WLHIV had screened for cervical cancer at the referral hospital and only 13% knew how to prevent high-risk HPV. No participants had received an HPV vaccination. Older age, higher education, and knowledge of the HPV vaccine were associated with higher likelihood of cervical cancer screening (P < 0.05). In FGDs, barriers to utilising the services included user fees, fear of the procedure impacting fertility, age and gender of the provider, and long waiting times. Conclusion: Despite integration with HIV services, the utilisation of cervical cancer screening was low among WLHIV and implementation barriers contributed to low utilisation.

Antiretroviral therapy outcomes among adolescents and young adults in a Tertiary hospital in Kenya.

BACKGROUND: Limited data is available on the treatment outcomes of HIV infected adolescents and young adults (AYA) in sub-Saharan Africa. HIV-infected adolescents and young adults (AYA) are at high risk of developing antiretroviral treatment failure. OBJECTIVE: To determine the clinical, immunological and virologic outcomes of AYA at a tertiary hospital in Kenya. METHODOLOGY: A longitudinal study was conducted among AYA age 10-24 years attending Kenyatta National Hospital comprehensive care center. Clinical data was abstracted from electronic medical records for study participants with at least 6 months of follow-up using a structured data abstraction sheet. RESULTS: A total of 250 AYA age 10 to 24 years were included. The median age was 16 years. The median CD4 cell count was 650.6 cells/mm3 (IQR 350.7-884.0). More than half (60.6%) of AYA had a CD4 cell count higher than 500 cells/mm3. Overall, 76.9% of AYA had achieved viral suppression (viral load <1000 copies/ml). There was a significant increase in virologic failure with higher age and late adolescents and young adults were more likely to have a viral load > 1000 copies/ml p<0.012. CONCLUSION: The overall virologic suppression in this cohort of AYA was sub-optimal. Both immunological and virologic outcomes were worse among late adolescents (18-19 years) and young adults (20-24 years).

Experiences With Safer Conception Services for HIV-Serodiscordant Couples at a Referral Hospital in Nairobi, Kenya.

Human immunodeficiency virus-serodiscordant couples are an important source of new HIV infections in Africa. When trying to conceive, uninfected partners may be at high risk of infection if the infected partner is not virally suppressed. Multiple strategies targeting safer conception exist, but these services are limited. However, when services are available and used, serodiscordant couples can be protected from HIV transmission, and safe to have children if desired. To successfully introduce, integrate, promote, and optimize the service delivery of safer conception with HIV care, it is crucial to understand how HIV-serodiscordant couples perceive and experience these services. Further, viral load monitoring can be critical to safer conception, but there is limited literature on how it informs the decision of the partners about conception. This qualitative study describes the knowledge, perceptions, and experiences of both safer conception services and viral load monitoring among 26 HIV-serodiscordant couples seeking safer conception care at a referral hospital in Nairobi, Kenya. In-depth interviews of HIV-serodiscordant couples were conducted from April to July 2017, and transcripts were analyzed to identify the themes central to the experience of safer conception services of couples and viral load monitoring. Serodiscordant couples reported success in using some of the safer conception methods and had positive experiences with healthcare providers. However, despite using the services, some were concerned about HIV transmission to the seronegative partner and baby, while others faced challenges when using pre-exposure prophylaxis (PrEP) and vaginal insemination. Overall, their motivation to have children overcame their concern about HIV transmission, and they welcomed discussions on risk reduction. Moreover, supportive clinic staff was identified as key to facilitating trust in safer conception methods. Furthermore, viral load monitoring was identified as integral to safer conception methods, an emerging theme that requires further evaluation, especially where routine viral load monitoring is not performed. In conclusion, healthcare providers offering safer conception services should build trust with couples, and recognize the need for continual couple counseling to encourage the adoption of safer conception services.

Positive and Healthy Living Program Manual Development for Young People Living With HIV at the Comprehensive Care Center at the Kenyatta National Hospital: An Open Pilot Implementation Trial.

Background: Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) remains a great challenge among young people in Kenya. Young people living with HIV are faced with a lot of challenges that are often overlooked and may have an impact on their treatment adherence and overall well-being. This calls for interventions that are age-appropriate and which tap into the psychosocial problems they experience. This is a protocol of a proposed study aimed at developing a facilitator-led peer support manual called the "Positive and Healthy Living Program" that will be the basis for running support groups with young people at the Comprehensive Care Center (CCC) at the Kenyatta National Hospital (KNH). Methods: We will carry out our study in two phases. The first phase will focus on the development of the manual and training of peer-facilitators. The second phase will make use of a pilot trial research design using both qualitative and quantitative approaches. It will be carried out among 10-24 year-olds attending CCC at KNH, and will consist of three groups: Tumaini Group (10-14 years), Amani Group (15-19 years), and Hodari Group (20-24 years). The groups will participate in an eight-session support group, whose activities will focus on four domains: social-recreation, psychotherapy, peer-modeling, and psychoeducation. Quantitative data will be collected using laboratory measures of Viral Load and CD4 as well as socio-psychological assessment tools. Qualitative data will be collected through interviews with the young people and peer facilitators. We will conduct a descriptive analysis which will describe the key features of the dataset and bivariate analyses will examine the association between variables. The change will be measured at baseline and post-treatment. The interviews will be coded into themes and we will generate experiential categories from the data around the effectiveness of the program, the peer facilitators' experience of providing support, how the young people respond to the program, and its influence on their overall well-being. Discussion: We expect that the peer facilitators will find this manualized treatment acceptable and the eight-sessions group intervention will be feasible for the three age groups. We hypothesize that there will be improvements detected with regards to reported adherence and viral load, self-esteem, depression, and psychological functioning.

Factors affecting uptake and completion of isoniazid preventive therapy among HIV-infected children at a national referral hospital, Kenya: a mixed quantitative and qualitative study.

BACKGROUND: Tuberculosis (TB) is the most common opportunistic infection and the leading cause of death in people living with HIV (PLHIV). HIV-infected children are at a higher risk of TB infection and disease compared to those without HIV. Isoniazid preventive therapy (IPT) is an effective intervention in preventing progression of latent TB infection to active TB. The World Health Organization (WHO) currently recommends that all children aged > 12 months and adults living with HIV in whom active TB has been excluded should receive a 6-months course of IPT as part of a comprehensive package of HIV care. Despite this recommendation, the uptake of IPT among PLHIV has been suboptimal globally. This study sought to determine the factors affecting IPT uptake and completion among HIV-infected children in a large HIV care centre in Nairobi, Kenya. METHOD: This was a cross-sectional mixed methods study comprising of quantitative and qualitative study designs. Medical records of 225 HIV-infected children aged 1 to < 10 years, in care in the Kenyatta National Hospital Comprehensive Care Centre (KNH CCC) were retrospectively reviewed, and 8 purposively selected healthcare providers and 18 consecutively selected caregivers of children were interviewed. RESULTS: IPT uptake among CLHIV in care in the KNH CCC was 68% (152/225) while the treatment completion rate was 82% (94/115). IPT-related health education and counselling were the main facilitators of IPT uptake and completion, while fear of adverse drug reaction, pill burden and lack of an integrated monitoring and evaluation system for IPT were the major barriers. CONCLUSION: The IPT uptake in this study was low and fell short of the set global target of > 90%. The completion rate was however acceptable. There is an urgent need to address the identified barriers.

Trends, treatment outcomes, and determinants for attrition among adult patients in care at a large tertiary HIV clinic in Nairobi, Kenya: a 2004-2015 retrospective cohort study.

BACKGROUND: Understanding trends in patient profiles and identifying predictors for adverse outcomes are key to improving the effectiveness of HIV care and treatment programs. Previous work in Kenya has documented findings from a rural setting. This paper describes trends in demographic and clinical characteristics of antiretroviral therapy (ART) treatment cohorts at a large urban, referral HIV clinic and explores treatment outcomes and factors associated with attrition during 12 years of follow-up. METHODS: This was a retrospective cohort analysis of HIV-infected adults who started ART between January 1, 2004, and September 30, 2015. ART-experienced patients and those with missing data were excluded. The Cochran-Armitage test was used to determine trends in baseline characteristics over time. Cox proportional hazards models were used to determine the effect of baseline characteristics on attrition. RESULTS: ART uptake among older adolescents (15-19 years), youth, and young adults increased over time (p=0.0001). Independent predictors for attrition included (adjusted hazard ratio [95% CI]) male sex: 1.30 (1.16-1.45), p=0.0001; age: 15-19 years: 1.83 (1.26-2.66), p=0.0014; 20-24 years: 1.93 (1.52-2.44), p=0.0001; and 25-29 years: 1.31 (1.11-1.54), p=0.0012; marital status - single: 1.27 (1.11-1.44), p=0.0005; and divorced/separated: 1.56 (1.30-1.87), p=0.0001; urban residence: 1.40 (1.20-1.64), p=0.0001; entry into HIV care following hospitalization: 1.31 (1.10-1.57), p=0.0026, or transfer from another facility: 1.60 (1.26-2.04), p=0.0001; initiation of ART more than 12 months after the date of HIV diagnosis: 1.36 (1.19-1.55), p=0.0001, and history of a current or past opportunistic infection (OI): 1.15 (1.02-1.30), p=0.0284. CONCLUSION: Although ART uptake among adolescents and young people increased over time, this group was at increased risk for attrition. Single marital status, urban residence, history of hospitalization or OI, and delayed initiation of ART also predicted attrition. This calls for focused evidence-informed strategies to address attrition and improve outcomes.

Lay beliefs about hypertension among HIV-infected adults in Kenya.

OBJECTIVE: Hypertension affects 23% of Kenyans and is the most prevalent modifiable risk factor for cardiovascular disease. Despite this, hypertension awareness and treatment adherence is very low. We conducted a qualitative study to explore lay beliefs about hypertension among HIV-infected adults to inform the development of culture sensitive hypertension prevention and control program. METHODS: Eight focus group discussions were held for 53 HIV-infected adults at the HIV clinic in Kenya. RESULTS: Respondents had difficulties in describing hypertension. Hypertension was considered a temporary illness that is fatal and more serious than HIV. Stress was perceived as a main cause for hypertension with a large majority claiming stress reduction as the best treatment modality. Alcohol and tobacco use were not linked to hypertension. Obesity was cited as a cause of hypertension but weight control was not considered as a treatment modality even though the majority of our participants were overweight. Most participants did not believe hypertension could be prevented. CONCLUSION: Our findings suggest a limited understanding of hypertension among people living with HIV and points to an urgent need to integrate hypertension education programmes in HIV care facilities in Kenya. To effect change, these programmes will need to tie in the culture meaning of hypertension.

Trends in clinical characteristics and outcomes of Pre-ART care at a large HIV clinic in Nairobi, Kenya: a retrospective cohort study.

BACKGROUND: The success of antiretroviral therapy in resource-scarce settings is an illustration that complex healthcare interventions can be successfully delivered even in fragile health systems. Documenting the success factors in the scale-up of HIV care and treatment in resource constrained settings will enable health systems to prepare for changing population health needs. This study describes changing demographic and clinical characteristics of adult pre-ART cohorts, and identifies predictors of pre-ART attrition at a large urban HIV clinic in Nairobi, Kenya. METHODS: We conducted a retrospective cohort analysis of data on HIV infected adults (≥15 years) enrolling in pre-ART care between January 2004 and September 2015. Attrition (loss to program) was defined as those who died or were lost to follow-up (having no contact with the facility for at least 6 months). We used Kaplan-Meier survival analysis to determine time to event for the different modes of transition, and Cox proportional hazards models to determine predictors of pre-ART attrition. RESULTS: Over the 12 years of observation, there were increases in the proportions of young people (age 15 to 24 years); and patients presenting with early disease (by WHO clinical stage and higher median CD4 cell counts), p = 0.0001 for trend. Independent predictors of attrition included: aHR (95% CI): male gender 1.98 (1.69-2.33), p = 0.0001; age 20-24 years 1.80 (1.37-2.37), p = 0.0001), or 25-34 years 1.22 (1.01-1.47), p = 0.0364; marital status single 1.55 (1.29-1.86), p = 0.0001) or divorced 1.41(1.02-1.95), p = 0.0370; urban residency 1.83 (1.40-2.38), p = 0.0001; CD4 count of 0-100 cells/µl 1.63 (1.003-2.658), p = 0.0486 or CD4 count >500 cells/µl 2.14(1.46-3.14), p = 0.0001. CONCLUSIONS: In order to optimize the impact of HIV prevention, care and treatment in resource scarce settings, there is an urgent need to implement prevention and treatment interventions targeting young people and patients entering care with severe immunosuppression (CD4 cell counts <100 cells/µl). Additionally, care and treatment programmes should strengthen inter-facility referrals and linkages to improve care coordination and prevent leakages in the HIV care continuum.

Perceptions of HIV infected patients on the use of cell phone as a tool to support their antiretroviral adherence; a cross-sectional study in a large referral hospital in Kenya.

BACKGROUND: Clinical trials were conducted to assess the feasibility of using a cell phone text messaging-based system to follow up Human Immunodeficiency Virus (HIV) infected patients on antiretroviral (ARTs) and assess for improved adherence to their medication. However there is need to evaluate the perceptions of the HIV infected patients towards the use of these cell phones in an effort to better aid in the clinical management of their HIV infection. The objective of this study was therefore to determine the perceptions of HIV infected patients on the use of cell phone text messaging as a tool to support adherence to their ART medication. METHODS: A cross sectional survey was conducted among patients receiving Highly Active Anti-Retroviral Therapy (HAART) at the Kenyatta National Hospital Comprehensive Care Clinic in Nairobi between May and July, 2011. Pre-tested questionnaires were used to collect the socio-demographic and perceptions data. The recruitment of the participants was done using the random probability sampling method and statistical analysis of data performed using Statistical Package for Social Sciences (SPSS) version 16.0. RESULTS: A total of 500 HIV infected patients (Male-107, Female-307) aged 19-72 years were interviewed. The majority of individuals (99%) had access to cell phones and 99% of the HIV infected patients interviewed supported the idea of cell phone use in management of their HIV infection. A large proportion (46%) claimed that they needed cell phone access for medical advice and guidance on factors that hinder their adherence to medication and only 3% of them needed it as a reminder to take their drugs. The majority (72%) preferred calling the healthcare provider with their own phones for convenience and confidential purposes with only 0.4% preferring to be called or texted by the health care provider. Most (94%), especially the older patients, had no problem with their confidentiality being infringed in the process of the conversation as per the bivariate analysis results. CONCLUSION: Cell phone communications are acceptable and in fact preferable over cell phone reminders.

Effect of concurrent use of anti-retroviral therapy and levonorgestrel sub-dermal implant for contraception on CD4 counts: a prospective cohort study in Kenya.

INTRODUCTION: Simultaneous use of contraceptive hormones and anti-retroviral therapy (ART) may theoretically lessen the effectiveness of both. Women on ART need assurance that hormonal contraception is safe and effective. The sub-dermal implant is an ideal product to study: low and steady progestin release and no adherence uncertainties. We sought to determine if the medications' effectiveness is compromised. METHODS: We conducted a prospective cohort study among women on first line ART (stavudine or zidovudine and lamivudine+nevirapine). We recruited new implant users and matched them to women not using hormonal contraception, based on age and baseline CD4. Participants were followed prospectively for up to two years, recording serial CD4 measures and medical histories. We used generalized growth curve models and Wald chi-square tests to compare changes in CD4 counts across study groups. Prospective CD4 measures were censored (excluded) if any of the following events occurred: change in ART, implant removal or use of any hormonal contraception among controls. We examined incidence of opportunistic infection and pregnancy. RESULTS: We matched 48 implant users to 33 non-hormonal controls. Over time, CD4 counts for both groups rose slightly but did not deviate significantly from each other (p=0.44). Opportunistic infection rates did not differ between the groups. None of the implant users and one of the non-hormonal controls became pregnant during follow-up. CONCLUSIONS: This small study found concurrent use of contraceptive implants and ART to be safe and effective. Although other hormonal contraceptive products and ART regimens may interact in unknown ways, the results of this study are reassuring.

Predicted HIV-1 coreceptor usage among Kenya patients shows a high tendency for subtype d to be cxcr4 tropic.

BACKGROUND: CCR5 antagonists have clinically been approved for prevention or treatment of HIV/AIDS. Countries in Sub-Saharan Africa with the highest burden of HIV/AIDS are due to adopt these regimens. However, HIV-1 can also use CXCR4 as a co-receptor. There is hence an urgent need to map out cellular tropism of a country's circulating HIV strains to guide the impending use of CCR5 antagonists. OBJECTIVES: To determine HIV-1 coreceptor usage among patients attending a comprehensive care centre in Nairobi, Kenya. METHODS: Blood samples were obtained from HIV infected patients attending the comprehensive care centre, Kenyatta National Hospital in years 2008 and 2009. The samples were separated into plasma and peripheral blood mononuclear cells (PBMCs). Proviral DNA was extracted from PBMCs and Polymerase Chain reaction (PCR) done to amplify the HIV env fragment spanning the C2-V3 region. The resultant fragment was directly sequenced on an automated sequencer (ABI, 3100). Co-receptor prediction of the env sequences was done using Geno2pheno [co-receptor], and phylogenetic relationships determined using CLUSTALW and Neighbor Joining method. RESULTS: A total of 67 samples (46 treatment experienced and 21 treatment naive) were successfully amplified and sequenced. Forty nine (73%) sequences showed a prediction for R5 tropism while 18(27%) were X4 tropic. Phylogenetic analysis showed that 46(69%) were subtype A, 11(16%) subtype C, and 10(15%) subtype D. No statistical significant associations were observed between cell tropism and CD4+ status, patient gender, age, or treatment option. There was a tendency for more X4 tropic strains being in the treatment experienced group than the naive group: Of 46 treatment experiencing participants, 14(30%) harboured X4, compared with 4(19%) of 21 of the treatment-naïve participants, the association is however not statistically significant (p = 0.31). However, a strong association was observed between subtype D and CXCR4 co- receptor usage (p = 0.015) with 6(60%) of the 10 subtype D being X4 tropic and 4(40%) R5 tropic. CONCLUSION: HIV-1 R5 tropic strains were the most prevalent in the study population and HIV infected patients in Kenya may benefit from CCR5 antagonists. However, there is need for caution where subtype D infection is suspected or where antiretroviral salvage therapy is indicated.

Hyponatremia, hypochloremia, and hypoalbuminemia predict an increased risk of mortality during the first year of antiretroviral therapy among HIV-infected Zambian and Kenyan women.

Early mortality rates after initiating antiretroviral therapy (ART) are high in sub-Saharan Africa. We examined whether serum chemistries at ART initiation predicted mortality among HIV-infected women. From May 2005 to January 2007, we enrolled women initiating ART in a prospective cohort study in Zambia and Kenya. We used Cox proportional hazards models to identify risk factors associated with mortality. Among 661 HIV-infected women, 53 (8%) died during the first year of ART, and tuberculosis was the most common cause of death (32%). Women were more likely to die if they were both hyponatremic (sodium <135 mmol/liter) and hypochloremic (chloride <95 mmol/liter) (37% vs. 6%) or hypoalbuminemic (albumin <34 g/liter, 13% vs. 4%) when initiating ART. A body mass index <18 kg/m(2) [adjusted hazard ratio (aHR) 5.3, 95% confidence interval (CI) 2.6-10.6] and hyponatremia with hypochloremia (aHR 4.5, 95% CI 2.2-9.4) were associated with 1-year mortality after adjusting for country, CD4 cell count, WHO clinical stage, hemoglobin, and albumin. Among women with a CD4 cell count >50 cells/µl, hypoalbuminemia was also a significant predictor of mortality (aHR=3.7, 95% CI 1.4-9.8). Baseline hyponatremia with hypochloremia and hypoalbuminemia predicted mortality in the first year of initiating ART, and these abnormalities might reflect opportunistic infections (e.g., tuberculosis) or advanced HIV disease. Assessment of serum sodium, chloride, and albumin can identify HIV-infected patients at highest risk for mortality who may benefit from more intensive medical management during the first year of ART.

How late is too late? Timeliness to scheduled visits as an antiretroviral therapy adherence measure in Nairobi, Kenya and Lusaka, Zambia.

Collecting self-reported data on adherence to highly active antiretroviral therapy (HAART) can be complicated by patients' reluctance to report poor adherence. The timeliness with which patients attend visits might be a useful alternative to estimate medication adherence. Among Kenyan and Zambian women receiving twice daily HAART, we examined the relationship between self-reported pill taking and timeliness attending scheduled visits. We analyzed data from 566 Kenyan and Zambian women enrolled in a prospective 48-week HAART-response study. At each scheduled clinic visit, women reported doses missed over the preceding week. Self-reported adherence was calculated by summing the total number of doses reported taken and dividing by the total number of doses asked about at the visit attended. A participant's adherence to scheduled study visits was defined as "on time" if she arrived early or within three days, "moderately late" if she was four-seven days late, and "extremely late/missed" if she was more than eight days late or missed the visit altogether. Self-reported adherence was <95% for 29 (10%) of 288 women who were late for at least one study visit vs. 3 (1%) of 278 who were never late for a study visit (odds ratios [OR] 10.3; 95% confidence intervals [95% CI] 2.9, 42.8). Fifty-one (18%) of 285 women who were ever late for a study visit experienced virologic failure vs. 32 (12%) of 278 women who were never late for a study visit (OR 1.7; 95% CI 1.01, 2.8). A multivariate logistic regression model controlling for self-reported adherence found that being extremely late for a visit was associated with virologic failure (OR 2.0; 95% CI 1.2, 3.4). Timeliness to scheduled visits was associated with self-reported adherence to HAART and with risk for virologic failure. Timeliness to scheduled clinic visits can be used as an objective proxy for self-reported adherence and ultimately for risk of virologic failure.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.