Richard Ndivo

Triple-Antiretroviral Prophylaxis to Prevent Mother-To- Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy.

Evaluation of syndromic management of sexually transmitted infections within the Kisumu Incidence Cohort Study

Summary While laboratory aetiological diagnosis is considered the gold standard for diagnosis and management of sexually transmitted infections (STIs), syndromic management has been presented as a simplified and affordable approach for STI management in limited resource settings. STI signs and symptoms were collected using staff-administered computer-assisted personal interview and audio computer-assisted self-interview. Participants underwent a medical examination and laboratory testing for common STIs. The performance of syndromic management was assessed on the agreement between interviewing methods as well as accurate diagnosis. We screened 846 participants, of whom 88 (10.4%) received syndromic STI diagnosis while 272 (32.2%) received an aetiological diagnosis. Agreement between syndromic and aetiological diagnoses was very poor (overall kappa = 0.09). The most prevalent STI was herpes simplex virus type 2 and the percentage of persons with any STI was higher among women (48.6%) than men (15.6%, p < 0.0001). Agreement between audio computer-assisted self-interview and computer-assisted personal interview interviewing methods for syndromic diagnosis of STIs ranged from poor to good. Our findings suggest that syndromic management of STIs is not a sufficient tool for STI diagnosis in this setting; development and improvement of STI diagnostic capabilities through laboratory confirmation is needed in resource-limited settings.

Nevirapine-associated hepatotoxicity and rash among HIV-infected pregnant women in Kenya.

Background: Few studies have evaluated the risk of nevirapine (NVP)-associated hepatotoxicity among HIV-infected pregnant women with a CD4 count ≥250 cells/mm3. Methods: We enrolled HIV-infected pregnant Kenyan women who initiated triple antiretroviral therapy (ART) at 34 weeks gestation. We compared the rates of severe hepatotoxicity (grades 3–4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) with NVP and nelfinavir (NFV), respectively. Results: We initiated triple ART in 522 pregnant women; severe hepatotoxicity and rash-associated hepatotoxicity occurred in 14 (3%) and 9 (2%) women, respectively. Women who initiated NVP had higher rates of severe hepatotoxicity (5% vs 1%; P = .03) and rash-associated hepatotoxicity (4% vs 0%; P = .003) when compared with NFV. Among women who initiated NVP (n = 254), a baseline CD4 count ≥250 cells/mm3 was not associated with severe hepatotoxicity (5% vs 3%; P = .52) or rash-associated hepatotoxicity (4% vs 3%; P = .69). Conclusion: Nevirapine use but not CD4 count ≥250 cells/mm3 was associated with hepatotoxicity.

Correlates of prevalent sexually transmitted infections among participants screened for an HIV incidence cohort study in Kisumu, Kenya.

We determined the prevalence of four sexually transmitted infections and the demographic and behavioural correlates associated with having one or more sexually transmitted infections among participants in an HIV incidence cohort study in Kisumu, western Kenya. Participants were enrolled from a convenience sample and underwent aetiologic sexually transmitted infection investigation. Demographic and behavioural information were collected and basic clinical evaluation performed. Multiple regression analysis was done to determine variables associated with having one or more sexually transmitted infections. We screened 846, 18- to 34-year-olds. One-third had at least one sexually transmitted infection with specific prevalence being: syphilis, 1.6%; gonorrhoea, 2.4%; herpes simplex virus type-2, 29.1%; chlamydia, 2.8%; and HIV, 14.8%. Odds of having any sexually transmitted infection were higher among participants who were women, were aged 20–24 or 30–34 years compared to 18–19 years, had secondary or lower education compared to tertiary education, were divorced, widowed or separated compared to singles, reported having unprotected sex compared to those who did not, reported previous sexually transmitted infection treatment, and tested HIV-positive. Multiple strategies are needed to address the overall high prevalence of sexually transmitted infections as well as the gender disparity found in this Kenyan population. Structural interventions may be beneficial in addressing educational and socio-economic barriers, and increasing the uptake of health-promoting practices.

Effect of point-of-care CD4 cell count results on linkage to care and antiretroviral initiation during a home-based HIV testing campaign: a non-blinded, cluster-randomised trial

BACKGROUND HIV disease staging with referral laboratory-based CD4 cell count testing is a key barrier to the initiation of antiretroviral treatment (ART). Point-of-care CD4 cell counts can improve linkage to HIV care among people living with HIV, but its effect has not been assessed with a randomised controlled trial in the context of home-based HIV counselling and testing (HBCT). METHODS We did a two-arm, cluster-randomised, controlled efficacy trial in two districts of western Kenya with ongoing HBCT. Housing compounds were randomly assigned (1:1) to point-of-care CD4 cell counts (366 compounds with 417 participants) or standard-of-care (318 compounds with 353 participants) CD4 cell counts done at one of three referral laboratories serving the study catchment area. In each compound, we enrolled people with HIV not engaged in care in the previous 6 months. All participants received post-test counselling and referral for HIV care. Point-of-care test participants received additional counselling on the result, including ART eligibility if CD4 was less than 350 cells per μL, the cutoff in Kenyan guidelines. Participants were interviewed 6 months after enrolment to ascertain whether they sought HIV care, verified through chart reviews at 23 local clinics. The prevalence of loss to follow-up at 6 months (LTFU) was listed as the main outcome in the study protocol. We analysed linkage to care at 6 months (defined as 1-LTFU) as the primary outcome. All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02515149. FINDINGS We enrolled 770 participants between July 1, 2013, and Feb 28, 2014. 692 (90%) had verified linkage to care status and 78 (10%) were lost to follow-up. Of 371 participants in the point-of-care group, 215 (58%) had linked to care within 6 months versus 108 (34%) of 321 in the standard-of-care group (Cox proportional multivariable hazard ratio [HR] 2·14, 95% CI 1·67-2·74; log rank p<0·0001). INTERPRETATION Point-of-care CD4 cell counts in a resource-limited HBCT setting doubled linkage to care and thereby improved ART initiation. Given the substantial economic and logistic hindrances to providing ART for all people with HIV in resource-limited settings in the near term, point of care CD4 cell counts might have a role in prioritising care and improving linkage to care. FUNDING US Centers for Disease Control and Prevention.

Investigation of HIV Incidence Rates in a High-Risk, High-Prevalence Kenyan Population Potential Lessons for Intervention Trials and Programmatic Strategies

Cost-effective HIV prevention programs should target persons at high risk of HIV acquisition. We conducted an observational HIV incidence cohort study in Kisumu, Kenya, where HIV prevalence is triple that of the national rate. We used referral and venue-sampling approaches to enroll HIV-negative persons for a 12-month observational cohort, August 2010 to September 2011, collected data using computer-assisted interviews, and performed HIV testing quarterly. Among 1292 eligible persons, 648 (50%) were excluded for HIV positivity and other reasons. Of the 644 enrollees, 52% were women who were significantly older than men (P < .01). In all, 7 persons seroconverted (incidence rate [IR] per 100 person-years = 1.11; 95% confidence interval [CI] 0.45-2.30), 6 were women; 5 (IR = 3.14; 95% CI 1.02-7.34) of whom were ≤25 years. Most new infections occurred in young women, an observation consistent with other findings in sub-Saharan Africa that women aged ≤25 years are an important population for HIV intervention trials in Africa.

Correlates of prevalent HIV infection among adults and adolescents in the Kisumu incidence cohort study, Kisumu, Kenya

We estimated HIV prevalence and identified correlates of HIV infection among 1106 men and women aged 16–34 years residing in Kisumu, Kenya. Demographic, sexual, and other behavioural data were collected using audio computer-assisted self-interview in conjunction with a medical examination, real-time parallel rapid HIV testing, and laboratory testing for pregnancy, gonorrhoea, chlamydia, syphilis, and herpes simplex virus type 2. Multivariate logistic regression was used to identify variables associated with prevalent HIV infection by gender. Overall HIV prevalence was 12.1%. HIV prevalence among women (17.1%) was approximately two-and-one-half times the prevalence among men (6.6%). Odds of HIV infection in men increased with age (aOR associated with one-year increase in age = 1.21, CI = 1.07–1.35) and were greater among those who were uncircumcised (aOR = 4.42, CI = 1.41–13.89) and those who had an herpes simplex virus type 2-positive (aOR = 3.13, CI = 1.12–8.73) test result. Odds of prevalent HIV infection among women also increased with age (aOR associated with one-year increase in age = 1.16, CI = 1.04–1.29). Women who tested herpes simplex virus type 2 positive had more than three times the odds (aOR = 3.85, CI = 1.38–10.46) of prevalent HIV infection compared with those who tested herpes simplex virus type 2 negative. Tailored sexual health interventions and programs may help mitigate HIV age and gender disparities.

Determinants and experiences of repeat pregnancy among HIV-positive Kenyan women - A mixed-methods analysis

Objective To identify factors associated with repeat pregnancy subsequent to an index pregnancy among women living with HIV (WLWH) in western Kenya who were enrolled in a 24-month phase-II clinical trial of triple-ART prophylaxis for prevention of mother-to-child transmission, and to contextualize social and cultural influences on WLWH’s reproductive decision making. Methods A mixed-methods approach was used to examine repeat pregnancy within a 24 month period after birth. Counselor-administered questionnaires were collected from 500 WLWH. Forty women (22 with a repeat pregnancy; 18 with no repeat pregnancy) were purposively selected for a qualitative interview (QI). Simple and multiple logistic regression analyses were performed for quantitative data. Thematic coding and saliency analysis were undertaken for qualitative data. Results Eighty-eight (17.6%) women had a repeat pregnancy. Median maternal age was 23 years (range 15-43 years) and median gestational age at enrollment was 34 weeks. In multiple logistic regression analyses, living in the same compound with a husband (adjusted odds ratio (AOR): 2.33; 95% confidence interval (CI): 1.14, 4.75) was associated with increased odds of repeat pregnancy (p ≤ 0.05). Being in the 30-43 age group (AOR: 0.25; 95% CI: 0.07, 0.87), having talked to a partner about family planning (FP) use (AOR: 0.53; 95% CI: 0.29, 0.98), and prior usage of FP (AOR: 0.45; 95% CI: 0.25, 0.82) were associated with a decrease in odds of repeat pregnancy. QI findings centered on concerns about modern contraception methods (side effects and views that they ‘ruined the womb’) and a desire to have the right number of children. Religious leaders, family, and the broader community were viewed as reinforcing cultural expectations for married women to have children. Repeat pregnancy was commonly attributed to contraception failure or to lack of knowledge about post-delivery fertility. Conclusions In addition to cultural context, reproductive health programs for WLWH may need to address issues related to living circumstances and the possibility that reproductive-decision making may extend beyond the woman and her partner.

Rash, hepatotoxicity and hyperbilirubinemia among Kenyan infants born to HIV-infected women receiving triple-antiretroviral drugs for the prevention of mother-to-child HIV transmission.

We compared adverse events among breast-feeding neonates born to Kenyan mothers receiving triple-antiretroviral therapy, including either nevirapine or nelfinavir. Nevirapine-exposed infants had an absolute increase in the risk of rash but no significant risk differences for hepatotoxicity or high-risk hyperbilirubinemia compared with nelfinavir-exposed infants. From an infant-safety perspective, nevirapine-based regimens given during pregnancy and breast-feeding are viable options where alternatives to breast milk are not safe, affordable or feasible.

Prevalence, incidence and correlates of HSV-2 infection in an HIV incidence adolescent and adult cohort study in western Kenya

Background Herpes simplex virus type 2 (HSV-2) infections are associated with increased risk of HIV transmission. We determined HSV-2 prevalence, incidence and associated risk factors, incidence among persons with indeterminate results, and prevalence of HSV-2/HIV co-infection among young adults (18–34 years) and adolescents (16–17 years) enrolled in an HIV incidence cohort study in western Kenya. Methods Participants (n = 1106; 846 adults) were screened and those HIV-1 negative were enrolled and followed-up quarterly for one year. HSV-2 was assessed using the Kalon enzyme immunoassay. HSV-2 incidence was calculated separately among HSV-2 seronegative participants and those indeterminate at baseline. Logistic regression was used to estimate the odds of HSV-2 infection and Poisson regression was used to assess HSV-2 incidence and associated factors. Results Overall, HSV-2 prevalence was 26.6% [95% confidence interval (CI): 23.9–29.4] and was higher in adults (31.5% [95% CI: 28.3–34.9]) than adolescents (10.7% [95% CI: 7.1–15.3]). Factors associated with prevalent HSV-2 included female gender, increasing age, HIV infection, history of sexually transmitted infection, low level of education, multiple sexual partners, and being married, divorced, separated or widowed. Overall HSV-2 incidence was 4.0 per 100 person-years (/100PY) 95% CI: 2.7–6.1 and was higher in adults (4.5/100PY) and females (5.1/100PY). In multivariable analysis only marital status was associated with HSV-2 incidence. Among 45 participants with indeterminate HSV-2 results at baseline, 22 seroconverted, resulting in an incidence rate of 53.2 /100PY [95% CI: 35.1–80.9]. Inclusion of indeterminate results almost doubled the overall incidence rate to 7.8 /100 PY [95% CI: 5.9–10.5]. Prevalence of HIV/HSV-2 co-infection was higher in female adults than female adolescents (17.1 [95% CI: 13.6–21.0] versus 3.4 [95% CI: 1.1–7.8]). Conclusion The high incidence rate among persons with indeterminate results underscores the public health concerns for HSV-2 spread and underreporting of the HSV-2 burden. Careful consideration is needed when interpreting HSV-2 serology results in these settings.