Residual disease and HPV persistence after cryotherapy for cervical intraepithelial neoplasia grade 2/3 in HIV-positive women in Kenya.

OBJECTIVE: To assess residual cervical intraepithelial neoplasia (CIN) 2/3 disease and clearance of high-risk (hr) human papillomavirus (HPV) infections at 6 months after cryotherapy among HIV-positive women. DESIGN: Follow-up study. METHODS: 79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy) and after cryotherapy (cells). RESULTS: At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI): 66.4-85.9). 18 women (22.8%) had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART) were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2-15.0) among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9-70). The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively. CONCLUSIONS: Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity.

Male, mobile, and moneyed: loss to follow-up vs. transfer of care in an urban African antiretroviral treatment clinic.

OBJECTIVES: The purpose of this study was to analyze characteristics, reasons for transferring, and reasons for discontinuing care among patients defined as lost to follow-up (LTFU) from an antiretroviral therapy (ART) clinic in Nairobi, Kenya. DESIGN: The study used a prospective cohort of patients who participated in a randomized, controlled ART adherence trial between 2006 and 2008. METHODS: Participants were followed from pre-ART clinic enrollment to 18 months after ART initiation, and were defined as LTFU if they failed to return to clinic 4 weeks after their last scheduled visit. Reasons for loss were captured through phone call or home visit. Characteristics of LTFU who transferred care and LTFU who did not transfer were compared to those who remained in clinic using log-binomial regression to estimate risk ratios. RESULTS: Of 393 enrolled participants, total attrition was 83 (21%), of whom 75 (90%) were successfully traced. Thirty-seven (49%) were alive at tracing and 22 (59%) of these reported having transferred their antiretroviral care. In the final model, transfers were more likely to have salaried employment [Risk Ratio (RR), 2.7; 95% confidence interval (CI), 1.2-6.1; p=0.020)] and pay a higher monthly rent (RR, 5.8; 95% CI, 1.3-25.0; p=0.018) compared to those retained in clinic. LTFU who did not transfer care were three times as likely to be men (RR, 3.1; 95% CI, 1.1-8.1; p=0.028) and nearly 4 times as likely to have a primary education or less (RR, 3.8; 95% CI, 1.3-10.6; p=0.013). Overall, the most common reason for LTFU was moving residence, predominantly due to job loss or change in employment. CONCLUSION: A broad definition of LTFU may include those who have transferred their antiretroviral care and thereby overestimate negative effects on ART continuation. Interventions targeting men and considering mobility due to employment may improve retention in urban African ART clinics. CLINICAL TRIALS: The study's ClinicalTrials.gov identifier is NCT00273780.

Comparing Papanicolau smear, visual inspection with acetic acid and human papillomavirus cervical cancer screening methods among HIV-positive women by immune status and antiretroviral therapy.

BACKGROUND: A rigorous comparison of cervical cancer screening methods utilizing data on immune status, antiretroviral therapy (ART) and colposcopy-directed biopsy has not been performed among HIV-positive women. METHODS: Between June and November 2009, 500 HIV-positive women were enrolled at an HIV treatment clinic in Nairobi, Kenya, and underwent Papanicolau (Pap) smear, visual inspection with acetic acid (VIA), human papillomavirus (HPV) and colposcopy-directed biopsy (gold standard). Positive Pap smear (ASCUS+, LSIL+, HSIL+), VIA, HPV and their combinations were compared with CIN2/3+. Sensitivity, specificity and AUC (sensitivity and 1-specificity) were compared using pairwise tests and multivariate logistic regression models that included age, CD4⁺ cell count and ART duration. RESULTS: Of 500 enrolled, 498 samples were collected. On histology, there were 172 (35%) normal, 186 (37%) CIN1, 66 (13%) CIN2, 47 (9%) CIN3 and 27 (5%) indeterminate. Pap (ASCUS+) was the most sensitive screening method (92.7%), combination of both Pap (HSIL+) and VIA positive was the most specific (99.1%) and Pap (HSIL+) had the highest AUC (0.85). In multivariate analyses, CD4⁺ cell count of 350 cells/µl or less was associated with decreased HPV specificity (P = 0.002); ART duration of less than 2 years was associated with decreased HPV (P = 0.01) and VIA (P = 0.03) specificity; and age less than 40 years was associated with increased VIA sensitivity (P < 0.001) and decreased HPV specificity (P = 0.005). CONCLUSION: Pap smear is a robust test among HIV-positive women regardless of immune status or ART duration. Results should be cautiously interpreted when using HPV among those younger, immunosuppressed or on ART less than 2 years, and when using VIA among those aged 40 years or more.

Increased incidence of symptomatic peripheral neuropathy among adults receiving stavudine- versus zidovudine-based antiretroviral regimens in Kenya.

The incidence of peripheral neuropathy (PN) among adults initiating antiretroviral therapy (ART) containing stavudine (d4T) versus zidovudine (ZDV) is not well described. We compared 1-year incidence between d4T- and ZDV-based regimens in adults initiating ART in a programmatic setting in Kenya. Of 1,848 adults on ART, 1,579 (85 %) initiated d4T-based and 269 (15 %) initiated ZDV-based regimens. One-year incidence of symptomatic PN per 100 person-years was 21.9 (n=236) among d4T users and 6.9 (n=7) among ZDV users (P=0.0002). D4T was associated with 2.7 greater risk of PN than ZDV (adjusted hazard ratio, 2.7, P=0.009). In settings with continued d4T use, such as Africa, the effects of d4T on PN compared to ZDV should be considered when choosing ART regimens.

Cervical HIV-1 RNA shedding after cryotherapy among HIV-positive women with cervical intraepithelial neoplasia stage 2 or 3.

OBJECTIVE: To determine the effect of cryotherapy on HIV-1 cervical shedding. DESIGN: Prospective cohort study. METHODS: Five hundred HIV-positive women enrolled at an HIV treatment clinic in Nairobi, Kenya were screened for cervical cancer. Women diagnosed with cervical intraepithelial neoplasia stage 2 or 3 (CIN 2/3) by histology were offered cryotherapy treatment. The first 50 women had cervical swabs taken at baseline and at 2 and 4 weeks following treatment. Swabs were analyzed for HIV-1 RNA and compared using General Estimating Equation (GEE) with binomial or Gaussian links. RESULTS: Of the 50 women enrolled, 40 were receiving antiretroviral therapy (ART) and 10 were not receiving ART at the time of cryotherapy and during study follow-up. Among all women, the odds of detectable cervical HIV-1 RNA did not increase at 2 weeks [odds ratio (OR) 1.18; 95% confidence interval (CI) 0.65-2.13] or 4 weeks (OR 1.29; 95% CI 0.71-2.33) following cryotherapy. Among 10 women not receiving ART, the OR of detectable shedding at 2 weeks was higher, but not statistically significant (OR 4.02; 95% CI 0.53-30.79; P = 0.2), and at 4 weeks remained unchanged (OR 1.00; 95% CI 0.27-3.74). CONCLUSION: There was no increase in detectable cervical HIV-1 RNA among HIV-positive women after cryotherapy. The risk of HIV-1 transmission after cryotherapy may not be significant, particularly among women already on ART at the time of cervical treatment. However, further investigation is needed among women not receiving ART.

Cervical squamous intraepithelial lesions among HIV-positive women on antiretroviral therapy in Kenya.

BACKGROUND: The prevalence of cervical squamous intraepithelial lesions (SIL) among HIV-infected women on antiretroviral therapy in sub-Saharan Africa has not been well described. METHODS: HIV-infected women enrolled in an HIV treatment clinic in Nairobi, Kenya were offered free cervical screening with Papanicolaou (Pap) smear testing if they were 30 to 39 years of age and on antiretroviral therapy. Women with SIL were compared to those without SIL with univariate analyses and logistic regression. RESULTS: Of 595 eligible women, 267 accepted Pap testing and had available cytology results, of whom 258 (97%) were on a non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen. Median duration of antiretroviral therapy was 13 months [interquartile range (IQR), 8-19]. Abnormal cytology was found in 123 women (46%) with 70 women (26%) having low grade squamous intraepithelial lesions (LSIL), 22 (8%) high grade squamous intraepithelial lesions (HSIL), 30(11%) atypical squamous cells of unknown significance (ASCUS) and 1 (0.4%) atypical glandular cells (AGC). Women with SIL had lower median CD4 cell count (239 vs 287 cells/mm3; P=0.02), lower income (<70 USD per month: 57% vs 38%; P=0.01), and less regular condom use (24% vs 40%; P=0.02) compared to those with no SIL. Duration and type of antiretroviral regimen were not significantly associated with SIL. CONCLUSION: SIL is prevalent among women on antiretroviral therapy and is associated with immunosuppression, low income, and less frequent condom use. Cervical cancer screening and counseling on condom use should be routinely offered to HIV-infected women in antiretroviral treatment clinics in Africa.